Tables: Preferred and Alternative Therapies for HIV-Associated Opportunistic Infections

Opportunistic Infection	Preferred Therapy	Alternative Therapy	Other Comments
Bacterial Enteric Infections	Empiric Therapy Pending Definitive Diagnosis	For People With HIV and CD4 Count >500 Cells/mm³, 1–2 Days of Loose Stool Without Fever or Blood in Stool Oral hydration, no further workup, and no antibiotics For People With HIV and CD4 Count 200–500 Cells/mm³ With Diarrhea Severe Enough to Compromise Quality of Life or the Ability to Work Azithromycin 500 mg PO daily for 5 days (BIII), or Ciprofloxacin 500–750 mg PO every 12 hours for 5 days (BIII) For People With HIV and Severe Disease (e.g., CD4 Count <200 Cells/mm³ or Concomitant AIDS-Defining Illness and With Clinically Severe Diarrhea [≥6 Liquid Stools Per Day or Bloody Stool and/or Accompanying Fever or Chills]) Hospitalization for diagnostic evaluation and IV antibiotics Ceftriaxone IV 1–2 g every 24 hours (BIII) Note: If Campylobacter or Shigella bacteremia is suspected, a carbapenem is preferred (BIII). Therapy and duration should be adjusted based on microbiology and antibiotic sensitivity results. If no pathogen is identified and the patient recovers quickly, 5 days of therapy is recommended. For patients with persistent diarrhea (>14 days) without severe clinical signs, antibiotics therapy can be withheld until a diagnosis is made.		Diagnostic fecal specimens should be obtained before initiation of empiric antimicrobial therapy. If a pathogen is identified, antibiotic susceptibilities should be performed to confirm and inform antibiotic choices, given increased reports of antibiotic resistance. Oral or IV rehydration (if indicated) should be given to patients with diarrhea (AIII). Antimotility agents should be avoided if there is concern about inflammatory diarrhea, including CDI (BIII). Risk of bacteremia increases with decreasing CD4 count. If no clinical response is observed after 3‍–‍4 days, consider a follow-up stool culture with antibiotic susceptibility testing or alternative diagnostic tests (e.g., toxin assays, molecular testing) to evaluate alternative diagnoses, antibiotic resistance, or drug–drug interaction (BIII). MSM may be at increased risk for antibiotic-resistant enteric infections.
Campylobacteriosis	For Mild Disease If CD4 Count >200 Cells/mm³ No therapy unless symptoms persist for more than several days (CIII) For Mild to Moderate Disease (If Susceptible) Azithromycin 500 mg PO daily for 5 days (BIII) (not recommended for patients with bacteremia [AIII]), or Ciprofloxacin 500–‍750 mg PO (or 400 mg IV) every 12 hours for 7‍–‍10 days (BIII) For Campylobacter Bacteremia Ciprofloxacin 500–750 mg PO (or 400 mg IV) every 12 hours for ≥14 days if the isolate is sensitive (BIII) plus an aminoglycoside (BIII) to limit the emergence of antibiotic resistance For Recurrent Infections Duration of therapy may be extended to 2–‍6 weeks (BIII).	For Mild to Moderate Disease (If Susceptible) Levofloxacin 750 mg (PO or IV) every 24 hours (BIII) Add an aminoglycoside to fluoroquinolone in bacteremic patients (BIII) to limit the emergence of antibiotic resistance.	Oral or IV rehydration if indicated (AIII) Antimotility agents should be avoided (BIII). Third-generation cephalosporins are not reliably active, and use of alternative cell wall–active agents, such as carbapenems, may be necessary in severely ill people who require empiric IV therapy until antimicrobial susceptibilities return. In the United States in 2018, 29% of C. jejuni isolates were resistant to ciprofloxacin and 2% were resistant to azithromycin; among C. coli isolates, 40.5% were resistant to fluoroquinolone and 13.3% were resistant to azithromycin. Effective ART may reduce the frequency, severity, and recurrence of Campylobacter infections.
Clostridium difficile Infection (CDI)	For Severe or Nonsevere CDI Fidaxomicin 200 mg PO twice daily for 10 days (AI) For Recurrent CDI 2021 IDSA CDI Guidelines suggest use of fidaxomicin over oral vancomycin because it has a greater likelihood for a sustained clinical response at 30 days (AI).	For Severe or Nonsevere CDI Vancomycin 125 mg PO four times daily for 10 days (AI) For Nonsevere CDI If Neither Fidaxomicin nor Vancomycin Is Available Metronidazole 500 mg (PO) three times daily for 10 days (CI) Recurrent CDI Vancomycin is an acceptable option (see IDSA Guideline for tapered and pulsed regimens) (AI). FMT may be considered after three CDI episodes (i.e., an initial and two recurrent episodes) (CIII)	Severe CDI: white blood cell count ≥15,000 cells/mL or serum creatinine concentrations >1.5 mg/dL; nonsevere CDI: white blood cell count <15,000 cells/mL and serum creatinine concentrations <1.5 mg/dL
Salmonellosis	All people with HIV and salmonellosis should receive antimicrobial treatment due to an increase of bacteremia (by 20-fold to 100-fold) and mortality (by up to sevenfold) compared with individuals without HIV (AIII).	Oral or IV rehydration if indicated (AIII) Antimotility agents should be avoided (BIII). The role of long-term secondary prophylaxis in patients with recurrent Salmonella bacteremia is not well established. Must weigh the benefits against the risks of long-term antibiotic exposure (BIII). Effective ART may reduce the frequency, severity, and recurrence of salmonella infections.
For Invasive Disease (Suspected or Confirmed) Ceftriaxone IV 1–2 g every 24 hours pending susceptibilities (BIII) For Nontyphoidal Salmonella Gastroenteritis (With or Without Bacteremia) (If Susceptible) Ciprofloxacin 500–750 mg PO (or 400 mg IV) every 12 hours (AIII) Duration of Therapy For Gastroenteritis Without Bacteremia If CD4 count ≥200 cells/mm³: 7–‍14 days (BIII) If CD4 count <200 cells/mm³: minimum of 2 weeks (may extend to up to 6 weeks if with severe disease) (BIII) For Gastroenteritis With Bacteremia If CD4 count ≥200/mm³: 14 days or longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present) (BIII) If CD4 count <200 cells/mm³: 2–‍6 weeks (BIII) Secondary Prophylaxis Should Be Considered For Patients With— Recurrent Salmonella bacteremia (BIII), or Recurrent gastroenteritis (with or without bacteremia) with CD4 count <200 cells/mm³ with severe diarrhea (BIII)	For Nontyphoidal Salmonella Gastroenteritis (With or Without Bacteremia) (If Susceptible) Levofloxacin 750 mg (PO or IV) every 24 hours (BIII), or Moxifloxacin 400 mg (PO or IV) every 24 hours (BIII), or TMP-SMX (160 mg/‌800 mg) PO (or IV) every 12 hours (BIII), or Ceftriaxone 1–2 g IV every 24 hours (BIII)
Shigellosis	Ciprofloxacin 500–750 mg PO (or 400 mg IV) every 12 hours (if MIC <0.12 µg/mL) (AIII) Duration of Therapy Gastroenteritis: 5–7 days (AIII) (except ciprofloxacin [5–‍10 days] and azithromycin [5 days]) Bacteremia: ≥14 days (BIII) Recurrent infections: Up to 6 weeks (BIII) In Severely Ill Patients Requiring Empiric Parenteral Therapy While Awaiting Susceptibility Consider initiating a carbapenem until antimicrobial susceptibilities are available (BIII). Note: Increased resistance of Shigella to fluoroquinolones in the United States. Alternative antibiotics should be considered if ciprofloxacin MIC is ≥0.12 µg/mL (BIII).	Levofloxacin 750 mg (PO or IV) every 24 hours (BIII), or Trimethoprim 160 mg/sulfamethoxazole 800 mg PO or IV every 12 hours for 5–‍7 days (BIII), or Azithromycin 500 mg PO daily for 5 days (BIII), or Ceftriaxone 1–2 g IV every 24 hours (BIII) Note: Azithromycin and TMP-SMX are not recommended for treatment of bacteremia. Note: Azithromycin-resistant Shigella spp. have been reported in MSM with HIV.	Therapy may slightly shorten the duration of illness and/or prevent the spread of infection (AIII). Oral or IV rehydration if indicated (AIII) Antimotility agents should be avoided (BIII). Many Shigella strains that are resistant to fluoroquinolones exhibit resistance to other commonly used antibiotics. Antibiotic sensitivity testing of Shigella isolates from individuals with HIV should be performed routinely. Given increasing antimicrobial resistance and limited data showing that antibiotic therapy limits transmission, antibiotic treatment may be withheld in patients with CD4 count >500 cells/mm³ whose diarrhea resolves prior to culture confirmation of Shigella infection (CIII). Effective ART may decrease the risk of recurrence of Shigella infections.
Bartonellosis	For Bacillary Angiomatosis, Peliosis Hepatis, Bacteremia, and Osteomyelitis Doxycycline 100 mg PO or IV every 12 hours (AII), or Erythromycin 500 mg PO or IV every 6 hours (AII) CNS Infections (Doxycycline 100 mg +/- RIF 300 mg) PO or IV every 12 hours (AIII) Confirmed Bartonella Endocarditis (Doxycycline 100 mg IV plus RIF 300 mg PO or IV) every 12 hours for 6 weeks, then continue with doxycycline 100 mg IV or PO every 12 hours (BII) Other Severe Infections (Doxycycline 100 mg PO or IV +/- RIF 300 mg PO or IV) every 12 hours (BIII), or (Erythromycin 500 mg PO or IV every 6 hours) +/- RIF 300 mg PO or IV every 12 hours (BIII) Duration of Therapy At least 3 months (AII)	For Bacillary Angiomatosis, Peliosis Hepatis, Bacteremia, Osteomyelitis, and Other Severe Infection Azithromycin 500 mg PO daily (BIII) Clarithromycin 500 mg PO twice a day (BIII) Confirmed Bartonella Endocarditis (Doxycycline 100 mg IV every 12 hours plus gentamicin 1 mg/kg IV every 8 hours) for 2 weeks, then continue with doxycycline 100 mg IV or PO every 12 hours (BII)	When RIF is used, take into consideration the potential for significant interaction with ARV drugs and other medications (see Table 4 for dosing recommendations). If relapse occurs after initial (>3 month) course of therapy, long-term suppression with doxycycline or a macrolide is recommended as long as the CD4 count is <200 cells/mm³ (AIII).
Candidiasis (Mucocutaneous)	For Oropharyngeal Candidiasis—Initial Episodes (For 7–14 Days) Fluconazole 200 mg PO loading dose, followed by 100–200 mg PO daily (AI) For Esophageal Candidiasis (For 14–‍21 Days) Fluconazole 200-mg loading dose, followed by 100–200 mg (up to 400 mg) PO or IV daily (AI). (Consider oral suspension for people with difficulty swallowing.) For Uncomplicated Vulvovaginal Candidiasis Fluconazole 150 mg PO for one dose (AII), or Topical azoles (clotrimazole, butoconazole, miconazole, tioconazole, or terconazole) for 3–‍7 days (AII), or Ibrexafungerp 300 mg PO twice daily for 1 day (BI) For Severe or Recurrent Vulvovaginal Candidiasis Fluconazole 100–200 mg PO daily for ≥7 days (AII), or Topical antifungal ≥7 days (AII) For Recurrent Vulvovaginal Candidiasis Only (The following regimens include treatment for the acute episode plus treatment to reduce recurrence.) Oteseconazole 600 mg PO at Day 1, 450 mg at Day 2, followed by once-weekly 150-‍mg dosing starting at Day 14 for 11 weeks (AI) (for those who are not of reproductive potential); or Fluconazole 150 mg PO at Days 1, 4, and 7, followed by oteseconazole 150 mg PO daily at Days 14–20, followed by oteseconazole 150 mg once weekly starting at Day 28 for 11 weeks (Weeks 4–14) (AI) (for those who are not of reproductive potential); or Fluconazole 150 mg PO every 72 hours for three doses, followed by ibrexafungerp 300 mg PO twice daily 1 day per month for 6 months (BI). (Use an effective form of contraception during treatment and for 4 days after the last dose.)	For Oropharyngeal Candidiasis—Initial Episodes (For 7–‍14 Days) Oral Therapy Itraconazole oral solution 200 mg PO daily (BI), or Posaconazole oral suspension 400 mg PO twice a day for 1 day, then 400 mg daily (BI), or Posaconazole tablet 300 mg PO twice a day for 1 day, then 300 mg daily (BI) Topical Therapy Miconazole mucoadhesive buccal 50-‍mg tablet once daily; apply to mucosal surface over the canine fossa once daily (do not swallow, chew, or crush tablet.) (BI), or Clotrimazole troches 10 mg PO five times daily (BI), or Nystatin suspension 4–‍6 mL four times a day (BII) For Esophageal Candidiasis (For 14–‍21 Days) Itraconazole oral solution 200 mg PO daily (AI), or Isavuconazole 400 mg PO loading dose, followed by 100 mg PO daily (BI), or Isavuconazole 400 mg PO once weekly (BI), or Voriconazole 200 mg PO or IV twice a day (BI), or Posaconazole oral suspension 400 mg PO twice a day for 1 day, then 400 mg daily (BI), or Posaconazole tablet 300 mg PO twice a day for 1 day, then 300 mg daily (BI), or Lipid formulation of amphotericin B 3–‍4 mg/kg IV daily (BI), or Caspofungin 70 mg IV loading dose, followed by 50 mg IV daily (BI), or Micafungin 150 mg IV daily (BI), or Anidulafungin 100 mg IV once, then 50 mg IV daily (BI) For Azole-Refractory Candida glabrata Vaginitis Boric acid vaginal suppository 600 mg once daily for 14 days (BII)	Chronic or prolonged use of azoles may promote the development of resistance. Systemic azoles may have significant drug–drug interactions with ARV drugs. A higher relapse rate for esophageal candidiasis is seen with echinocandins use than with fluconazole. Suppressive therapy is usually not recommended (CIII) unless patients have frequent or severe recurrences. If the Decision Is to Use Suppressive Therapy Oropharyngeal Candidiasis Fluconazole 100 mg PO once daily or three times weekly (BI) Esophageal Candidiasis Fluconazole 100–‍200 mg PO daily (BI), or Posaconazole oral suspension 400 mg PO twice a day (BII), or Posaconazole tablet 300 mg PO daily (BII) Vulvovaginal Candidiasis Fluconazole 150 mg PO once weekly (BII), or Oteseconazole 600 mg at Day 1 and 450 mg at Day 2 for treatment of the acute episode, followed by once-weekly 150-mg doses starting at Day 14 for 11 weeks (AI) (for those who are not of reproductive potential); or Fluconazole 150 mg at Days 1, 4, and 7 for treatment of the acute episode, followed by oteseconazole 150 mg daily at Days 14–20, followed by oteseconazole 150 mg once weekly starting at Day 28 for 11 weeks (Weeks 4–14) (AI) (for those who are not of reproductive potential); or Ibrexafungerp 300 mg twice daily 1 day per month for 6 months (BI). (Use an effective form of contraception during treatment and for 4 days after the last dose.)
Chagas Disease (American Trypanosomiasis)	For Acute or Reactivated Disease Benznidazole 5–8 mg/kg/day PO in two divided doses for 60 days (BIII) (commercially available at https://www.benznidazoletablets.com/en; most experts recommend a daily maximum of 300 mg), or Nifurtimox (Lampit) 8–10 mg/kg/day PO in three divided doses for 60 days (BIII) (commercially available through retail sources)	None	Treatment is effective in reducing parasitemia and preventing clinical symptoms or slowing disease progression; however, these drugs have limited efficacy in achieving parasitological cure. Treatment is not recommended for patients with advanced chagasic cardiomyopathy. Duration of therapy has not been studied in patients with HIV. Initiation or optimization of ART is recommended for all people with HIV with concomitant Trypanosoma cruzi (AIII).
Coccidioidomycosis	Mild to Moderate Pulmonary Infection Fluconazole 400 mg PO daily (AII), or Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO twice a day (AII) Duration of therapy: clinical response to 3–6 months of therapy, CD4 count ≥250 cells/mm³, and viral suppression on ART (AII) Severe Pulmonary or Extrapulmonary Infection (Except Meningitis) Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily (AII), or Lipid formulation amphotericin B 3–‍5 mg/kg IV daily (AIII) Continue until clinical improvement, then switch to an azole (fluconazole 400 mg PO daily or itraconazole 200 mg PO twice daily) (BIII). Therapy should be continued for at least 12 months and usually much longer, and should be continued in patients with HIV viremia or with CD4 count <250 cells/mm³ (BIII). Meningeal Infections Fluconazole 800–1,200 mg PO daily (AII) Duration of therapy: lifelong (AII)	Mild to Moderate Pulmonary Infection For Patients Who Failed to Respond to Fluconazole or Itraconazole Voriconazole 400 mg PO twice daily on Day 1, then 200 mg PO twice a day (BIII) Posaconazole delayed release tablet 300 mg PO twice a day on Day 1, then 300 mg PO once daily (BIII), or Isavuconazole sulfate 372 mg PO every 8 hours for six doses, then 372 mg once daily (BIII) Severe Pulmonary or Extrapulmonary Infection (Except Meningitis) Some specialists will combine amphotericin B with a triazole (fluconazole or itraconazole, with itraconazole preferred for bone disease) as initial therapy and continue triazole once amphotericin B is stopped (CIII). Meningeal Infections Itraconazole 200 mg PO two or three times daily (BII), or Voriconazole 200–‍400 mg PO twice daily (BIII), or Posaconazole delayed release tablet 300 mg PO twice on Day 1, then 300 mg PO once daily (CIII), or Isavuconazole sulfate 372 mg PO every 8 hours for six doses, then 372 mg once daily (CIII) Intrathecal amphotericin B deoxycholate when triazole antifungals are ineffective (AIII)	Some patients with meningitis may develop hydrocephalus and require CSF shunting. Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of patients with HIV after discontinuation of triazole therapy (AII). See Table 4 for drug–drug interactions or triazole antifungal drugs and other drugs for treatment or prevention of OIs. Itraconazole, posaconazole, and voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bidirectional. Refer to Drug–Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines for dosage recommendations. Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities. Intrathecal amphotericin B should only be given in consultation with a specialist and administered by an individual with experience with the technique.
Community-Acquired Pneumonia (CAP)	Empiric antibiotic therapy should be initiated promptly for patients presenting with clinical and radiographic evidence consistent with bacterial pneumonia. The recommendations listed are suggested empiric therapy. The regimen should be modified as needed once microbiologic results are available (BIII). Providers must also consider the risk of opportunistic lung infections (e.g., PCP, TB), which may alter the empiric therapy. Empiric Outpatient Therapy A PO beta-lactam plus a PO macrolide (azithromycin or clarithromycin) (AII) Preferred Beta-Lactams High-dose amoxicillin or amoxicillin/clavulanate Alternative Beta-Lactams Cefpodoxime or cefuroxime, or Levofloxacin 750 mg PO once daily (AII), or moxifloxacin 400 mg PO once daily (AII), especially for patients with penicillin allergies Empiric Therapy for Hospitalized Patients With Nonsevere CAP An IV beta-lactam plus a macrolide (azithromycin or clarithromycin) (AI) Preferred Beta-Lactams Ceftriaxone, cefotaxime, or ampicillin-sulbactam Levofloxacin 750 mg IV once daily (AI), or moxifloxacin, 400 mg IV once daily (AI), especially for patients with penicillin allergies. Empiric Therapy for Hospitalized Patients With Severe CAP An IV beta-lactam plus IV azithromycin (AI), or An IV beta-lactam plus (levofloxacin 750 mg IV once daily or moxifloxacin 400 mg IV once daily) (AI) Preferred Beta-Lactams Ceftriaxone, cefotaxime, or ampicillin-sulbactam Empiric Therapy for Patients at Risk of Pseudomonas Pneumonia An IV antipneumococcal, antipseudomonal beta-lactam plus (ciprofloxacin 400 mg IV every 8–‍12 hours or levofloxacin 750 mg IV once daily) (AI) Preferred Beta-Lactams Piperacillin-tazobactam, cefepime, imipenem, or meropenem Empiric Therapy for Patients at Risk for Methicillin-Resistant Staphylococcus aureus Pneumonia Add vancomycin IV or linezolid (IV or PO) to the baseline regimen (AII). Addition of clindamycin to vancomycin (but not to linezolid) can be considered for severe necrotizing pneumonia to minimize bacterial toxin production (CII).	Empiric antibiotic therapy should be initiated promptly for patients presenting with clinical and radiographic evidence consistent with bacterial pneumonia. The recommendations listed are suggested empiric therapy. The regimen should be modified as needed once microbiologic results are available (BIII). Providers must also consider the risk of opportunistic lung infections (e.g., PCP, TB), which may alter the empiric therapy. Empiric Outpatient Therapy A PO beta-lactam plus PO doxycycline (CIII) Preferred Beta-Lactams High-dose amoxicillin or amoxicillin/clavulanate Alternative Beta-Lactams Cefpodoxime or cefuroxime Empiric Therapy for Hospitalized Patients With Nonsevere CAP An IV beta-lactam plus doxycycline (CIII) Empiric Therapy for Hospitalized Patients With Severe CAP For Penicillin-Allergic Patients Aztreonam IV plus (levofloxacin 750 mg IV once daily or moxifloxacin 400 mg IV once daily) (BIII) Empiric Therapy for Patients at Risk of Pseudomonas Pneumonia An IV antipneumococcal, antipseudomonal beta-‍lactam plus an IV aminoglycoside plus azithromycin (BII), or An IV antipneumococcal, antipseudomonal beta-‍lactam plus an aminoglycoside plus (levofloxacin 750 mg IV once daily or moxifloxacin 400 mg IV once daily) (BIII) For Penicillin-Allergic Patients Replace the beta-lactam with aztreonam (BIII).	Duration For most patients, 5–‍7 days Patients should be afebrile for 48–72 hours and clinically stable before stopping antibiotics. Longer duration is often required if severe CAP or bacteremia is present, and particularly if due to S. pneumoniae or complicated S. aureus pneumonia. Fluoroquinolones should be used with caution in patients in whom TB is suspected but is not being treated. Empiric therapy with a macrolide alone is not routinely recommended, because of increasing pneumococcal resistance (up to 30%) (BIII). Patients receiving a macrolide for MAC prophylaxis may have bacterial resistance to macrolide due to chronic exposure. For patients begun on IV antibiotic therapy, switching to PO should be considered when they are clinically improved and able to tolerate oral medications. Antibiotic chemoprophylaxis is generally not recommended because of the potential for developing drug resistance and drug toxicities (AI).
Cryptococcosis	For CNS and/or Disseminated Disease Induction Therapy (For ≥2 Weeks, Followed by Consolidation Therapy) In the United States and other settings where daily electrolytes and kidney function monitoring and electrolyte and IV fluid administration is possible— Liposomal amphotericin B 3–‍4 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day for 2 weeks (AII) (Note: Flucytosine dose should be adjusted in patients with renal dysfunction.) In resource-limited settings, as recommended by WHO— Liposomal amphotericin B 10 mg/kg IV as a single dose on Day 1, followed by flucytosine 25 mg/kg four times a day plus fluconazole 1,200 mg daily for 2 weeks (AI) If not improved clinically or remain clinically unstable, continue induction therapy until the CSF culture is confirmed to be negative (BIII). Consolidation Therapy (for ≥8 weeks, Followed by Maintenance Therapy) Fluconazole 800 mg PO daily (AI) For clinically stable patients with negative CSF cultures and ART has been started, dose can be reduced to 400 mg PO daily (AII) If CSF remains positive (but clinically stable) after 2 weeks of induction therapy, use one of the following two options for an additional 2 weeks before reducing the dose of fluconazole to 800 mg PO daily: Fluconazole 1,200 mg PO daily with flucytosine 25 mg/kg PO four times a day for 2 weeks (BIII) Fluconazole 1,200 mg PO daily for 2 weeks (BIII), or Note: Duration of consolidation therapy should be at least 8 weeks from the time of negative CSF culture (AII). Maintenance Therapy Fluconazole 200 mg PO daily for ≥1 year from initiation of antifungal therapy (AI) For Non-CNS Extrapulmonary (BIII) or Diffuse Pulmonary Disease (BIII) or People With Non-CNS Symptoms With Normal CSF and Serum CrAg ≥1:640 by LFA (or ≥1:160 by EIA or Latex Agglutination) (BII) Treatment is the same as for CNS cryptococcosis. For Non-CNS Focal Pulmonary Infiltrates (With Mild Symptoms) Fluconazole 400 mg daily for 6 to 12 months (duration guided by symptom resolution) (BIII) For Asymptomatic Antigenemia Without Meningitis and Serum CrAg <1:640 by LFA (or <1:160 by EIA or Latex Agglutination) Fluconazole: 800–1,200 mg PO daily for 2 weeks, followed by 400–800 mg PO daily for a total of 10 weeks, then fluconazole 200 mg PO daily for a total of 6 months plus effective ART (BIII)	For CNS and/or Disseminated Disease Induction Therapy (For ≥2 Weeks, Followed by Consolidation Therapy) Amphotericin B lipid complex 5 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day for 2 weeks (BII), or Amphotericin B deoxycholate 1 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day for 1 week, followed by fluconazole 1,200 mg PO daily for an additional week (BI) Additional Studied Induction Regimens (For 2 Weeks) Amphotericin B deoxycholate 0.7–‍0 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day (BI) Liposomal amphotericin B 3–‍4 mg/kg IV daily plus fluconazole 800–‍1,200 mg PO daily (BIII) Amphotericin B deoxycholate 0.7–‍0 mg/kg IV daily plus fluconazole 800–‍1,200 mg PO or IV daily (BI) Fluconazole 1,200 mg PO or IV daily plus flucytosine 25 mg/kg PO four times a day (BII) Consolidation Therapy (for ≥8 Weeks, Followed by Maintenance Therapy) If fluconazole is not available or not well tolerated: Itraconazole 200 mg PO twice a day for 8 weeks (CI) Maintenance Therapy If fluconazole is not available or not well tolerated: Itraconazole 200 mg PO twice a day (CI) If susceptibility studies have been performed and the fluconazole MIC is ≥16 µg/mL, the fluconazole dose may be increased to 400 mg daily (BIII). For Non-CNS Extrapulmonary (BIII) or Diffuse Pulmonary Disease (BIII) or People With Non-CNS Symptoms With Normal CSF and Serum CrAg ≥1:640 by LFA (or ≥1:160 by EIA or Latex Agglutination) (BII) Alternative treatment options are the same as for CNS cryptococcosis.	Addition of flucytosine to amphotericin B has been associated with more rapid sterilization of CSF and decreased risk for subsequent relapse. Patients receiving flucytosine should have either blood levels monitored (peak level 2 hours after dose should be 25–‍100 µg/mL) or at least twice weekly monitoring of complete blood counts for cytopenia. Dosage should be adjusted in patients with renal insufficiency (BII). Irrespective of which regimen is used, patients must be followed carefully in hospital for at least 7 days and ideally 14 days (AII). For patients with CNS disease, LP should be performed at Day 7 and Day 14 to ensure an appropriate clinical response and culture sterility. If increased ICP is documented, daily LP should be performed until the pressure is decreased into the normal range and symptoms have abated (AII). Opening pressure should always be measured when an LP is performed. Repeated LPs or CSF shunting are essential to effectively managing increased intracranial pressure. Corticosteroids and mannitol are ineffective in reducing ICP and are not recommended (AIII). Some specialists recommend a brief course of tapering dose of corticosteroid for management of severe IRIS symptoms (BIII). All people with non-CNS extrapulmonary symptoms and cryptococcal antigenemia should have their CSF sampled to rule out CNS disease. People with asymptomatic cryptococcal antigenemia, lower risk, and serum CrAg titer <1:80 by LFA (or <1:20 by EIA or latex agglutination) can be safely treated without lumbar puncture (AI). All others with asymptomatic cryptococcal antigenemia should undergo CSF sampling to rule out CNS disease.
Cryptosporidiosis	Aggressive oral and/or IV rehydration and replacement of electrolyte loss (AIII), and Symptomatic treatment of diarrhea with anti-motility agents (AIII), and ART initiation to achieve immune restoration to CD4 count > 100 cells/mm³ (AII).	No therapy has been shown to be effective without ART. Consider a trial of these agents in conjunction with ART, rehydration, and symptomatic treatment: Nitazoxanide 500–1,000 mg PO twice a day with food for at least 14 days (CIII), or Paromomycin 500 mg PO four times daily for 14–21 days (CIII)	Tincture of opium may be more effective than loperamide in management of diarrhea (CIII). Because diarrhea can cause lactase deficiency, patients should avoid milk products (CIII).
Cystoisosporiasis	For Acute Infection TMP-SMX (160 mg/800 mg) PO (or IV) four times daily for 10 days (AII), or TMP-SMX (160 mg/800 mg) PO (or IV) twice daily for 7 days (BI) In patients with persistent or worsening symptoms while on twice-daily dosing, consider increasing the daily dose and/or the duration to 3–‍4 weeks (BIII). IV TMP-SMX may be used for patients with potential or documented malabsorption. Chronic Maintenance Therapy (Secondary Prophylaxis) In People With CD4 Count <200 Cells/mm³ TMP-SMX (160 mg/800 mg) PO three times weekly (AI), or TMP-SMX (160 mg/‌800 mg) PO daily (AIII)	For Acute Infection Pyrimethamine^b 50–‍75 mg PO daily plus leucovorin 10–‍25 mg PO daily for 4 weeks (BIII), or Ciprofloxacin 500 mg PO or 400 mg IV twice daily for 7 days (CI) Chronic Maintenance Therapy (Secondary Prophylaxis) In People With CD4 Count <200 Cells/mm³ TMP-SMX (320 mg/1,600 mg) three times weekly (BIII), or Pyrimethamine^b 25 mg PO daily plus leucovorin 5–‍10 mg PO daily (BIII), or Ciprofloxacin 500 mg three times weekly (CI) as a second-line alternative	Fluid and electrolyte management in patients with dehydration (AIII) Nutritional supplementation for patients who are malnourished (AIII) Immune reconstitution with ART may result in fewer relapses; therefore, ART initiation should not be deferred (AIII).
Cytomegalovirus (CMV) Disease	CMV Retinitis Induction Therapy (Followed by Maintenance Therapy) Valganciclovir 900 mg PO every 12 hours for minimum 14–‍21 days, then maintenance therapy with valganciclovir 900 mg PO once daily (AI), or Ganciclovir 5 mg/kg IV every 12 hours for minimum 14–‍21 days, then maintenance therapy with valganciclovir 900 mg PO once daily (AI), or Ganciclovir 5 mg/kg IV every 12 hours for minimum 14–‍21 ‍‍days, then maintenance therapy with ganciclovir 5 mg/kg IV daily (AI) Note: Many clinicians prefer the IV formulation when retinitis is more central and sight-threatening or when adequate GI absorption is a concern; transition to oral valganciclovir can be considered when there is evidence of clinical response. CMV Retinitis—Immediate Sight-Threatening Lesions (Within 1,500 Microns of the Fovea or Optic Disc) In addition to systemic therapy (as listed above): intravitreal injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection), repeated weekly during the induction period until lesion inactivity is achieved (BIII), followed by systemic treatment alone for maintenance therapy. CMV Retinitis—Peripheral Lesions Valganciclovir 900 mg PO every 12 hours for minimum 14–‍21 days, then maintenance therapy with valganciclovir 900 mg PO once daily (AI) Duration of Maintenance Therapy Continue maintenance therapy for at least 3 months, and lesions are inactive, and CD4 count ≥100 cells/mm³for at least 3 months in response to ART (AII) CMV Esophagitis or Colitis Ganciclovir 5 mg/kg IV every 12 hours (AI); may switch to valganciclovir 900 mg PO every 12 hours when the patient can absorb and tolerate oral therapy (AIII). Valganciclovir 900 mg PO every 12 hours can be used in patients with mild disease (AIII). Duration: 21–42 days or until signs and symptoms have resolved (AIII) CMV Pneumonia Ganciclovir 5 mg/kg IV every 12 hours (BIII) Duration: ≥21 days or until signs and symptoms have resolved (CII) CMV Neurological Disease Ganciclovir 5 mg/kg IV every 12 hours plus foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours) (BIII). Duration: ≥21 days based on clinical response (AIII)	CMV Retinitis Induction Therapy (Followed by Maintenance Therapy) Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 14–21 days, then maintenance therapy with foscarnet 90 mg/kg or 120 mg/kg IV every 24 hours (BI), or Cidofovir 5 mg/kg IV every week for 2 weeks, then maintenance therapy with cidofovir 5 mg/kg IV every other week. Administer 1 L of normal saline before and, if additional fluid load can be tolerated, administer another 1 L of normal saline after each cidofovir infusion. Administer probenecid 2 g PO 3 hours before each cidofovir dose followed by 1 g PO 2 hours after the dose, and 1 g PO 8 hours after the dose (total of 4 g) (CI). CMV Retinitis—Immediate Sight-Threatening Lesions (Within 1,500 Microns of the Fovea or Optic Disc) In addition to systemic therapy (as listed above): intravitreal therapy as listed in the Preferred section CMV Esophagitis or Colitis Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours (BIII)—for patients with treatment-limiting toxicities to ganciclovir or with ganciclovir resistance; or Cidofovir (dosing as listed above) (CI) Duration: 21–42 days or until signs and symptoms have resolved (AIII) CMV Pneumonia Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours (BIII) Duration: ≥ 21 days or until signs and symptoms have resolved (CII)	CMV retinitis treatment should be individualized based on tolerance of systemic medications, prior exposure to anti-CMV drugs, and location of lesions as well as with the active participation of an ophthalmologist who is familiar with diagnosis and management of this retinal disease. Systemic therapy must be administered to prevent disease in the contralateral eye until immune reconstitution has occurred. After resolution of the acute non-ocular CMV disease and initiation of effective ART, chronic maintenance therapy is not routinely recommended for CMV GI disease, pneumonia, and central nervous system disease unless there is concurrent retinitis, there have already been recurrent infections, or severe disease was present initially Ophthalmologic monitoring is recommended during treatment and after discontinuation of maintenance therapy and is continued after immune reconstitution. See text for ophthalmic monitoring recommendations and frequency of follow-up. Initiate ART within 1–‍‎‍2 weeks after starting anti-CMV therapy for retinitis, esophagitis, colitis, or other end-organ diseases caused by CMV (BIII). With neurologic disease, including CMV encephalitis, ventriculitis, and radiculitis, the Panel recommends initiating ART within 2 weeks, although clinical judgment based on individual cases is needed (BIII). Immune recovery uveitis (IRU) may develop in the setting of immune reconstitution. See text for information on the treatment of IRU. Cidofovir should be avoided in patients with sulfonamide allergy because of cross-hypersensitivity with probenecid. For people with renal insufficiency, see Table 6 for information on dosing adjustments for valganciclovir, ganciclovir, foscarnet, and cidofovir.
Hepatitis B Virus (HBV) Disease	ART is recommended for all patients with HIV/HBV coinfection regardless of CD4 cell count and HBV DNA level (AII). The ART regimen must include drugs that are active against both HBV and HIV (AII). If CrCl ≥60 mL/min— (TAF [10 or 25 mg]^a plus FTC 200 mg) or (TAF 25 mg plus 3TC 300 mg) PO once daily (AII), or (TDF 300 mg plus [FTC 200 mg or 3TC 300 mg]) once daily (AII) If CrCl 30–59 mL/min— TAF (10 or 25 mg)^a plus FTC 200 mg PO once daily (AII) If CrCl <30 mL/min, Not on HD— Renally dosed entecavir (in place of TDF/[FTC or 3TC] or TAF/FTC) with a fully suppressive ART regimen (AIII), or ART with renally dose-adjusted TDF and (FTC or 3TC) can be used (AIII) if recovery of renal function is unlikely. If CrCl ≥15 to 29 mL/min, then ART with TAF (10 or 25 mg)^a once daily plus renally dose-adjusted FTC or 3TC is an option (AIII). Some clinicians may continue full-dose FTC or 3TC to allow for people to remain on fixed-dose TAF/FTC products. If on HD— Renally dose-adjusted TDF plus [FTC 200 mg or 3TC 300 mg once daily] (see Table 6) (AII) TAF [10 or 25 mg]^a plus FTC 200 mg PO once daily (given after HD on dialysis days) (AII) Duration Continue treatment indefinitely (AIII).	For People on NRTI-Sparing ART Entecavir 0.5 mg once daily may be used in place of (TAF or TDF) plus (3TC or FTC) (AIII).	Directly acting HBV drugs—such as emtricitabine, entecavir, lamivudine, and tenofovir—must not be given in the absence of a fully suppressive ART regimen to avoid selection of drug-resistant HIV (AI). Chronic administration of 3TC or FTC as the only HBV-active drug should be avoided because of the high rate of selection of HBV drug-resistance mutations (AI). People with 3TC-resistant HBV will have cross-resistance to FTC and partial resistance to entecavir, these agents should not be used (AI). If 3TC resistance is suspected or documented, TDF or TAF should be added to the ART regimen (AIII). When changing ART regimens, continue agents with anti-HBV activity (AIII). If anti-HBV therapy is discontinued and a flare occurs, therapy should be reinstituted because it can be potentially lifesaving (AIII). Because HBV reactivation can occur during treatment for HCV with direct-acting antivirals in the absence of anti-HBV therapy, all people with HIV/HBV coinfection who will be treated for HCV infection should be on HBV-active ART at the time of HCV treatment initiation (AIII). If immunosuppressive therapy is given, HBV reactivation can occur. For people who are HBsAg-positive, treatment for HBV infection should be administered (AII). For detailed recommendations, see Hepatitis B Virus Infection.
Hepatitis C Virus (HCV) Disease	For Treatment-Naive Patients Without Cirrhosis (Any Genotype or No Pre-Treatment Genotype) Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AI), or Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily for 12 weeks (AI) Characteristics that exclude patients from receiving simplified approach to therapy are outlined in Box 1 of the Hepatitis C Virus section. For Treatment-Naive Patients with Compensated Cirrhosis (Recommendations Based on Genotypes) Genotypes 1, 2, 4–6 Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AIII), or Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily for 12 weeks (AI) Genotype 3 Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AIII) For Treatment of Acute HCV Infection Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AII) or Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily for 12 weeks (AII)	For Treatment-Naive Patients with Compensated Cirrhosis (Recommendations Based on Genotypes) Genotypes 1, 2, 4–6 Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 12 weeks (CI) Genotype 3 Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 12 weeks (CI) or Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily with or without ribavirin for 12 weeks pending results of NS5A RAS testing (CI)	A simplified approach to HCV treatment can be used in treatment-naive patients with any genotype and without cirrhosis. This approach includes standardized treatment, with no on-treatment testing or in-person follow-up and limited follow-up to confirm SVR. See the Hepatitis C Virus section to review a summary of drug–drug interactions between HCV therapy and ARV drugs. HCV treatment should not be withheld solely due to perceived lack of adherence to ART or untreated HIV (BIII). Effort should be made to document SVR (HCV RNA less than lower limits of quantification) at least 12 weeks after completion of therapy (AI). Patients without cirrhosis who achieve SVR do not require continued liver disease monitoring. Recommendations for treatment after DAA failure are not provided. The reader is referred to the corresponding section in the AASLD/IDSA HCV treatment guidance.
Herpes Simplex Virus (HSV) Disease	Orolabial Lesions (For 5–‍10 Days) Valacyclovir 1 g PO twice a day (AIII), or Famciclovir 500 mg PO twice daily (AIII), or Acyclovir 400 mg PO three times daily (AIII) Initial Genital Lesions (For 7–‍10 Days) or Recurrent Genital Lesions (For 5–10 Days) Valacyclovir 1 g PO twice daily (AI), or Famciclovir 500 mg PO twice daily (AI), or Acyclovir 400 mg PO three times daily (AI) Severe Mucocutaneous and Visceral or Disseminated HSV Initial therapy: Acyclovir 10 mg/kg IV every 8 hours for 10–14 days (AIII) For mucocutaneous lesions, change to PO therapy (dose as above) once lesions begin to regress (AIII); continue PO therapy until lesions have completely healed (AIII). Some clinicians will extend the course of treatment for visceral or disseminated disease based on clinical response and degree of immunosuppression. Epithelial Keratitis Valacyclovir 1 g PO twice daily for 5–10 days (BIII), or Acyclovir 400 mg PO five times daily for 5–10 days (BIII), or Trifluridine eye drops (BIII) (see mpox for dosing), or Ganciclovir 0.15% gel: 1 drop into the affected eye five times a day (every 3 hours while awake) until re-epithelialization has occurred; then 1 drop three times a day for an additional 7 days (BIII) Stromal Keratitis (For ≥1 Year) Acyclovir 400 mg PO twice daily (AII) or valacyclovir 500 mg once daily (AIII), plus Prednisolone 1%: 1 drop into the affected eye six to eight times per day for at least 10 weeks followed by taper; exact course should be managed by ophthalmologist and based on individual patient course (AIII). HSV Meningitis (For 10–14 Days) (AIII) Initial therapy: Acyclovir 10 mg/kg IV every 8 hours After clinical improvement, change to valacyclovir 1 g PO three times a day HSV Encephalitis (For 14–‍21 Days) (CIII) Acyclovir 10 mg/kg IV every 8 hours Some clinicians will elect to extend the course based on clinical response and degree of immunosuppression. Chronic Suppressive Therapy Valacyclovir 500 mg PO twice daily (AI) May continue indefinitely, regardless of CD4 count; re-evaluate annually, particularly if immune reconstitution has occurred (BIII).	For Acyclovir-Resistant HSV (Based on Clinical Response, Typically for 21–28 Days or Longer) Preferred Therapy Foscarnet 40 mg/kg IV every 8–12 hours until clinical response (AI) Alternative Therapy Topical imiquimod 5% three times weekly (BIII), or Topical cidofovir 1% once daily (BIII), or Topical trifluridine 1% three times daily (BIII), or Topical foscarnet 1% five times daily (BIII), or IV cidofovir once weekly for 2 weeks, then every other week (CIII). See CMV Retinitis for information on concomitant probenecid and hydration. Chronic Suppressive Therapy Acyclovir 400 mg PO twice daily (AI), or Famciclovir 500 mg PO twice daily (AI), or Valacyclovir 500 or 1,000 mg PO once daily (CIII). See the Herpes Simplex Virus Disease section for additional information. May continue indefinitely, regardless of CD4 count; re-evaluate annually, particularly if immune reconstitution has occurred (BIII).	HSV infection can be treated with episodic therapy when symptomatic lesions occur or with daily suppressive therapy to prevent recurrences. For ophthalmic HSV disease, consultation with an ophthalmologist experienced with HSV ocular disease is strongly recommended (AIII). Topical formulations of trifluridine, cidofovir, and foscarnet are not commercially available but can be extemporaneously compounded. An expanded access program of oral pritelivir is available for immunocompromised patients with acyclovir-resistant HSV infection. See the AiCuris Pritelivir website. Chronic suppressive therapy is indicated for people with severe or frequent recurrences of genital herpes (AI), for people who want to minimize frequency of recurrences (AI), and to reduce the risk of genital ulcer disease in people with CD4 counts <250 cells/mm³ who are starting ART (BI). Recurrences following episodes of acyclovir-resistant HSV can be caused by either acyclovir-resistant or acyclovir-sensitive strains; after resolution of the acyclovir-resistant episode, suppressive therapy with acyclovir can be considered to prevent additional recurrences (CIII).
Histoplasmosis	Severe Disseminated Disease Induction Therapy (For ≥2 Weeks or Until Clinically Improved) Liposomal amphotericin B 3 mg/kg IV daily (AI) Maintenance Therapy (For ≥12 Months) Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO twice a day (AII) Mild to Moderate Disseminated Disease or Acute Pulmonary Histoplasmosis in Persons With CD4 <300 Cells/mm³ Both Induction and Maintenance Therapy (For ≥12 Months) Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO twice a day (AII) Meningitis Induction Therapy (4–6 Weeks Depending on Symptom Resolution and Improvement of CSF Findings) Liposomal amphotericin B 5 mg/kg IV daily (AIII) Maintenance Therapy (For ≥12 Months and Until Resolution of Abnormal CSF Findings) Itraconazole 200 mg PO two to three times a day (AIII), with dose adjustment based on serum itraconazole concentration Long-Term Suppression Therapy For Patients with Severe Disseminated or CNS Infection After Completion of ≥12 Months of Therapy (AIII) or Who Relapse Despite Appropriate Therapy (after reinduction therapy) (BIII) Itraconazole 200 mg PO daily (AIII)	Severe Disseminated Disease Induction Therapy Amphotericin B lipid complex 5 mg/kg IV daily (AIII) Maintenance Therapy (For ≥12 Months) Posaconazole extended-release tablet 300 mg PO twice a day for 1 day, then 300 mg PO once daily (BIII) Voriconazole 400 mg PO twice a day for 1 day, then 200 mg PO twice a day (BIII), or Fluconazole 800 mg PO daily (CII) Mild to Moderate Disseminated Disease or Acute Pulmonary Histoplasmosis in People With CD4 Count <300 Cells/mm³ Both Induction and Maintenance Therapy (For ≥12 Months) Posaconazole extended-release tabet 300 mg PO twice a day for 1 day, then 300 mg PO once daily (BIII) Voriconazole 400 mg PO twice a day for 1 day, then 200 mg PO twice a day (BIII), or Fluconazole 800 mg PO daily (CII) Meningitis Induction Therapy (4–6 Weeks Depending on Symptom Resolution and Improvement of CSF Findings) Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily (BIII) Maintenance Therapy (For ≥12 Months and Until Resolution of Abnormal CSF Findings) Voriconazole 400 mg PO twice a day for 1 day, then 200 mg twice a day (BIII), or For people who cannot tolerate itraconazole and voriconazole: Fluconazole 800 mg PO daily (CII) Long-Term Suppression Therapy Fluconazole 400 mg PO once daily (CII) Voriconazole 200 mg PO twice daily (BIII) Posaconazole 300 mg extended-release tablet PO once daily (BIII)	Itraconazole, posaconazole, and voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bidirectional. Refer to Drug–Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines for dosage recommendations. Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and ARV efficacy and reduce concentration-related toxicities. Random serum concentration of itraconazole between 1–‍2 µg/mL is recommended. Frequency and severity of toxicities increase when concentration is ≥5 µg/mL. The recommendations for posaconazole, voriconazole, and fluconazole are based on very limited clinical data and for people who are only moderately ill.
Human Herpesvirus-8 (HHV-8) Associated Diseases (Kaposi Sarcoma [KS], Primary Effusion Lymphoma [PEL], Multicentric Castleman’s Disease [MCD])	KS ACTG Stage T0 (Localized Involvement of Skin and/or Lymph Nodes and/or Minimal Oral Disease Only) ART (AII) alone, or ART plus liposomal doxorubicin (AIII), if disease does not respond to ART alone ACTG Stage T1 (Extensive and/or Symptomatic KS Skin Lesions, Extensive Oral Disease, Tumor-Associated Edema and/or Ulceration, or Any Visceral Involvement) ART plus liposomal doxorubicin (AI) MCD MCD without KS: ART plus rituximab (BII) MCD with KS: ART plus rituximab with liposomal doxorubicin (AII) PEL or HHV-8 DLBCL (With or Without KS) PEL or HHV-8-associated DLBCL: ART plus combination chemotherapy, such as EPOCH (AIII) PEL or HHV-8-associated DLBCL with MCD: ART plus dose-adjusted EPOCH plus rituximab (CII) KSHV-Associated Inflammatory Cytokine Syndrome After excluding MCD and PEL, ART plus rituximab with combination chemotherapy for concurrent KS (CII)	KS ACTG Stage T1 (Extensive and/or Symptomatic KS Skin Lesions, Extensive Oral Disease, Tumor-Associated Edema and/or Ulceration, or Any Visceral Involvement) ART plus paclitaxel, if liposomal doxorubicin is not available (AI), or to treat recurrence after treatment with liposomal doxorubicin (AII), or ART with oral pomalidomide plus thromboprophylaxis (e.g., low-dose aspirin 81 mg daily) (BII) MCD ART plus IV ganciclovir (or oral valganciclovir) with or without high-dose zidovudine—not for use in cases of multi-organ failure, such as renal and/or hepatic failure (CII)	Treatment should be undertaken in consultation with both oncology and infectious disease specialists, with additional input from centers specifically caring for people with HIV and cancer (AIII). All HHV-8–specific treatments should be given with ART (AI). ART given concurrently with chemotherapy should be chosen to minimize drug–drug interactions and additive toxicities (AIII). Systemic corticosteroids or other immunosuppressants in patients with KS should either be avoided or used under close observation, given the potential for exacerbation of KS (AIII). Although corticosteroids appear to be effective as an adjunctive therapy for MCD, they should be used with caution or avoided, especially in patients with concurrent KS, given potential for exacerbation of life-threatening KS (AIII). One-third of patients receiving rituximab may have subsequent exacerbations or emergence of KS.
Human Papillomavirus (HPV) Disease	Treatment of Genital Warts	Patients with HIV may have larger or more numerous warts and may not respond as well to therapy for genital warts when compared to individuals without HIV. Intralesional interferon is usually not recommended because of high cost, difficult administration, and potential for systemic side effects (CIII). In patients with HIV, the rate of recurrence of genital warts despite treatment is high. There is no consensus on the treatment of oral warts. Many treatments for anogenital warts cannot be used in the oral mucosa. Surgery is the most common treatment for oral warts that interfere with function or for aesthetic reasons.
Patient-Applied Treatment Options for Uncomplicated External Warts That Can Be Easily Identified by Patients Topical imiquimod 5% cream: Apply to genital warts at bedtime on three nonconsecutive nights per week for up to 16 weeks, until lesions are no longer visible. Each treatment should be washed with soap and water 6–‍10 hours after application (BII); or Topical podophyllotoxin (e.g., podofilox 0.5% solution or 0.5% gel): Apply to genital warts twice a day for 3 days, followed by 4 days of no therapy. Can be repeated weekly for up to four cycles (BIII); or Topical sinecatechins 15% ointment: Apply to affected areas three times a day for up to 16 weeks, until warts are completely cleared and not visible (BIII); or Topical cidofovir 1%: Daily for 5 days per week for 8 weeks (CIII). Topical formulation is not commercially available but may be compounded.	Provider-Applied Therapy for Complex or Multicentric Lesions, or Lesions Inaccessible to Patient, or Due to Patient or Provider Preference Cryotherapy (liquid nitrogen or cryoprobe): Apply until each lesion is thoroughly frozen. Repeat every 1–‍2 weeks for up to 4 weeks, until lesions are no longer visible (BIII). Some specialists allow the lesion to thaw, then freeze a second time in each session (BIII); or Trichloroacetic acid or bichloroacetic acid cauterization (80–90% aqueous solution): Apply to warts only and allow to dry until a white frost develops. Repeat weekly for up to 6 weeks, until lesions are no longer visible (BIII); or Intralesional cidofovir (15 mg/mL solution) injected directly into the wart (maximum 1 mL per session). May be repeated every 4 weeks for total of 3–‍4 treatments (CIII). Surgical excision (BIII) or laser surgery (CIII) for external or anal warts
Leishmaniasis	Visceral	For Leishmania infantum/chagasi Liposomal amphotericin B 3–‍5 mg/kg IV daily (AII), or Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on Days 1–5, 10, 17, 24, 31, 38) (AII) To achieve total dose of 20–‍60 mg/kg (AII) For Leishmania donovani Liposomal amphotericin B 5 mg/kg on Days 1, 3, 5, 7, 9, and 11 plus miltefosine 50 mg PO twice daily (for 28 days if from East Africa or 14 days if from Southeast Asia) (BI) Chronic Maintenance Therapy For Patients With CD4 Count <200 Cells/mm³ (AII) Liposomal amphotericin B 4 mg/kg IV every 2–4 weeks (AII)	For Leishmania infantum/chagasi or donovani Amphotericin B deoxycholate 0.5–‍0 mg/kg IV daily for total dose of 1.5–‍2.0 g (BII), or Pentavalent antimony (meglumine antimoniate) 20 mg/kg IV or IM daily for 28 days (BII) For Leishmania donovani Liposomal amphotericin B 3–‍5 mg/kg IV daily to achieve total dose of 20–‍60 mg/kg (AII), or Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on Days 1–‍5, 10, 17, 24, 31, 38) to achieve total dose of 20–‍60 mg/kg (AII), or For Indian L. donovani: Miltefosine ~2.5–‍3.0 mg/kg PO daily in two or three divided doses (maximum 150 mg daily) for 28 days (BII) Chronic Maintenance Therapy (Secondary Prophylaxis) Amphotericin B lipid complex 3 mg/kg IV every 21 days (BII), or Pentavalent antimony (meglumine antimoniate) 20 mg/kg IV or IM every 4 weeks (BII), or Pentamidine 4 mg/kg (maximum 300 mg) IV every 2–4 weeks (BII)	ART should be initiated or optimized as soon as possible (AIII). Pentavalent antimony is for investigational use only. For miltefosine, visit www.profounda.com.
Cutaneous	For Initial Infection Liposomal amphotericin B 4 mg/kg IV daily for 10 days (BIII) to achieve total dose of 20–60 mg/kg, or Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on Days 1–5, 10, 17, 24, 31, 38) to achieve total dose of 20–60 mg/kg (BIII), or Miltefosine 2.5 mg/kg/day PO in two or three divided doses for 28 days (maximum 150 mg per day) (BIII), or Pentavalent antimony (meglumine antimoniate) 20 mg/kg IV or IM daily for 28 days (BIII) Chronic Maintenance Therapy May be indicated in immunocompromised patients with multiple relapses (CIII) Drugs and doses same as for visceral leishmaniasis	Possible Options Cryotherapy, or Topical paromomycin, or Intralesional pentavalent antimony (meglumine antimoniate) or pentamidine, or PO or IV fluconazole (L. major and L. mexicana) IV pentamidine Local heat therapy No data exist for any of these agents in patients with HIV; choice and efficacy are dependent on species of Leishmania.	ART should be initiated or optimized as soon as possible (AIII). Pentavalent antimony is for investigational use only. For miltefosine, visit www.profounda.com.
Malaria	Because Plasmodium falciparum malaria can progress within hours from mild symptoms or low-grade fever to severe disease or death, all HIV-infected patients with confirmed or suspected P. falciparum infection should be hospitalized for evaluation, initiation of treatment, and observation (AIII). Treatment recommendations for HIV-infected patients are the same as for HIV-uninfected patients (AIII). Choice of therapy is guided by the degree of parasitemia, the species of Plasmodium, the patient’s clinical status, region of infection, and the likely drug susceptibility of the infected species, and can be found at https://www.cdc.gov/malaria.	When suspicion for malaria is low, antimalarial treatment should not be initiated until the diagnosis is confirmed.	For treatment recommendations for specific regions, clinicians should refer to the following web link: http://www.cdc.gov/malaria. or call the CDC Malaria Hotline: 770-488-7788, Monday–Friday, 8 a.m.–4:30 p.m. ET; or 7704887100 after hours.
Microsporidiosis	For GI Infections Caused by Enterocytozoon bienuesi Initiate or optimize ART with immune restoration to CD4 count >100 cells/mm³(AII); plus Manage dehydration and diarrhea with fluid support (AII) and malnutrition and wasting with nutritional supplements (AIII). For Intestinal and Disseminated (Not Ocular) Infections Caused by Microsporidia Other Than E. bienuesi and Vittaforma corneae Albendazole 400 mg PO twice daily (AII), continue until CD4 count >200 cells/mm³ for >6 months after initiation of ART (BIII) For Disseminated Disease Caused by Trachipleistophora or Anncaliia Itraconazole 400 mg PO daily plus albendazole 400 mg PO twice daily (CIII) For Ocular Infection Topical fumagillin bicylohexylammonium (Fumidil B) eye drops 3 mg/mL in saline (fumagillin 70 µg/mL): Two eye drops every 2 hours for 4 days, then two eye drops four times daily (investigational use only in United States) (BII) plus albendazole 400 mg PO twice daily, for management of systemic infection (BIII) If CD4 Count >200 Cells/mm³ Continue until symptoms resolve (CIII). If CD4 Count ≤200 Cells/mm³ Continue until resolution of ocular symptoms and CD4 count increases to >200 cells/mm³ for >6 months in response to ART (BIII).	For GI Infections Caused by E. bienuesi Fumagillin 60 mg/day (BII) and TNP-470 (a synthetic analog of fumagillin) (BIII) may be effective, but neither is available in the United States. Nitazoxanide (1,000 mg twice daily) may have some effect, but response may be minimal in patients with low CD4 cell counts (CIII).	Anti-motility agents can be used for diarrhea control if required (BIII).
Mpox	For People With Mild to Moderate Disease Who Are Not at Risk for Severe Disease Supportive care, including adequate pain control (BIII), and referral to clinical trials, if available (CIII). CDC can provide additional guidance to clinicians with patient management questions (see Other Comments for contact information). For Severe Disease or People at Risk for Severe Disease (See Other Comments for Definition) Tecovirimat 600 mg PO every 12 hours (40 to <120 kg) or every 8 hours (≥120 kg) for 14 days (BIII) within 30 minutes of a fatty meal, or Tecovirimat 200 mg IV every 12 hours for 14 days (35 to <120 kg) or 300 mg IV every 12 hours (≥120 kg) infused over 6 hours (BIII) if concern exists regarding altered GI absorption capacity, inability to take PO, or severity of illness Adjunctive Therapy Cidofovir 5 mg/kg/week IV for two doses with saline hydration before and after therapy and probenecid 2 g PO 3 hours before the dose followed by 1 g PO 2 hours after the dose and 1 g PO 8 hours after the dose (total of 4 g) (BIII), or Brincidofovir 200 mg PO once weekly for two doses (BIII), or VIGIV 6,000–9,000 units/kg IV single dose (BIII) For Ocular Mpox Tecovirimat 600 mg PO every 12 hours (40 to <120 kg) or every 8 hours (≥120 kg) for 14 days (BIII) within 30 minutes of a fatty meal, plus Trifluridine (Viroptic) 1 drop into affected eye(s) every 2 hours when awake (max: 9 drops/day) until reepithelialization, then every 4 hours (min: 5 drops/day) for 7 days, or until all periocular lesions have healed (BIII) in consultation with an ophthalmologist (BIII) Prolonged use of trifluridine beyond 21 days might cause corneal epithelial toxicity and should be avoided (AII).	None	People with severe mpox or are at high risk for severe mpox should receive directed mpox antiviral treatment (BIII) with early consultation with CDC or an expert in mpox treatment and prompt use of combination therapy, ideally at the time of the first medical encounter and after considering the risks and benefits (CIII). Contact: [email protected] or 770-488-7100 Tecovirimat, brincidofovir, and VIGIV are available via expanded access or emergency IND. People with severe immunocompromise might benefit from extended treatment (i.e., >14 days) if new confirmed mpox lesions occur or existing lesions or symptoms worsen despite treatment (CIII). Effective ART should be initiated as soon as possible (AIII). Definition for Severe Disease: Hemorrhagic disease; lesions affecting ≥25% of body surface that may be confluent, necrotic, and/or hemorrhagic in appearance or cause sepsis; disease resulting in airway compromise or affecting the nervous system; cardiac and/or neurologic disease; ocular or periorbital infections; other conditions requiring hospitalization. Consult the CDC’s Tecovirimat webpage for more details. Definition for at Risk for Severe Disease: Not virologically suppressed, CD4 counts <200 cells/mm³, have another immunocompromising condition, have atopic dermatitis/other conditions affecting skin integrity, or are children, pregnant, or breastfeeding. Consult the CDC’s Tecovirimat webpage for more details.
Mycobacterium avium Complex (MAC) Disease	At Least Two Drugs as Initial Therapy to Prevent or Delay Emergence of Resistance (AII) Clarithromycin 500 mg PO twice daily (AI) plus ethambutol 15 mg/kg PO daily (AI), or Azithromycin 500–600 mg plus ethambutol 15 mg/kg PO daily (AII) if drug interaction or intolerance precludes the use of clarithromycin. Duration At least 12 months (AII) Shorter duration may be considered. CD4 count should be >100 cells/mm³ for ≥6 months in response to ART before discontinuation of MAC therapy (CIII).	Some experts would add a third drug if more severe disease is present. Rifabutin 300 mg PO daily (dose adjustment may be necessary based on drug interactions) (CI) Refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table of the Mycobacterium tuberculosis section for dosing recommendations. Some experts would add a fourth drug if the risk of mortality is high, emergence of drug resistance is likely, CD4 count <50 cells/mm³, high mycobacterial loads (>2 log₁₀ CFU/mL of blood) are present, or effective ART is absent (CIII). A fluoroquinolone (CIII) (e.g., moxifloxacin 400 mg PO daily or levofloxacin 500 mg PO daily), or An injectable aminoglycoside (CIII) (e.g., amikacin 10–‍15 mg/kg IV daily or streptomycin 1 g IV or IM daily).	Testing of susceptibility to clarithromycin and azithromycin is recommended. NSAIDs can be used for moderate to severe symptoms attributed to IRIS (BIII). If IRIS symptoms persist, a short course (i.e., 4–‍8 weeks) of a systemic corticosteroid (equivalent to 20–40 mg of prednisone daily) can be used (BII). Bedaquiline, tedizolid, linezolid, and omadacycline have demonstrated in vitro activity against clinical isolates of MAC; these might also be considered in people with refractory MAC disease.
Mycobacterium tuberculosis (TB) Disease: Drug-Susceptible TB	Refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis section for dosing recommendations. Intensive Phase (8 Weeks) INH (plus pyridoxine) plus (RIF or RFB) plus PZA plus EMB PO daily (AI) If drug susceptibility report shows sensitivity to INH and RIF, then EMB may be discontinued before the end of 2 months (AI). Continuation Phase (Duration Depends on Site and Severity of Infection as noted below) INH (plus pyridoxine) plus (RIF or RFB) PO daily (AII) Total Duration of Therapy for Drug-Susceptible TB Pulmonary, Uncomplicated TB: 6 months (BII) Pulmonary TB with Positive Culture at 8 Weeks of TB Treatment, or Severe Cavitary or Disseminated Extrapulmonary TB: 9 months (BII) TB Meningitis: 9–12 months (BII) Extrapulmonary TB in Other Sites: 6 months (BII)	Only for Patients Receiving an Efavirenz-Based ARV Regimen; Not Recommended for Extrapulmonary TB Intensive Phase (8 Weeks) INH plus RPT 1,200 mg plus moxifloxacin 400 mg plus PZA plus pyridoxine 25–50mg PO daily (AI)^c Continuation Phase (9 Weeks) INH plus RPT 1200 mg plus moxifloxacin 400 mg plus pyridoxine 25–50mg PO daily (AI)	DOT is recommended for all patients (AII). All rifamycins may have significant pharmacokinetic interactions with ARV drugs; please refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis section and the Drug–Drug Interactions section of the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations. Therapeutic drug monitoring should be considered in patients receiving rifamycin and interacting ART. Adjunctive corticosteroids for TB meningitis (AII): Dexamethasone 0.3–‍0.4mg/kg/day for 2–‍4 weeks, then taper by 0.1 mg/kg per week until 0.1 mg/kg, then 4 mg per day, and taper by 1 mg/week for total of 12 weeks. At doses above 16 mg, dexamethasone is a CYP3A4 inducer and can decrease certain ARVs that are substrates of CYP3A4 (e.g., DOR, RPV, and protease inhibitors). Consultation with a pharmacist is recommended. Adjunctive corticosteroid is not recommended for patients with TB pericarditis (AI). See text for recommendations on preventing and managing paradoxical TB-IRIS, including prednisone dosing recommendations.
Mycobacterium tuberculosis (TB) Disease: Drug-Resistant TB	Refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis section for dosing recommendations. Empiric Therapy for Suspected Resistance to Rifamycin^d +/- Resistance to Other Drugs INH (plus pyridoxine) plus PZA plus EMB plus (moxifloxacin or levofloxacin) plus (linezolid or amikacin^e) (BII) Confirmed Resistance to INH (Moxifloxacin or levofloxacin) plus (RIF or RFB) plus EMB plus PZA for 6 months (BII) Confirmed Resistance to Rifamycin +/- Other Drugs (AI) For 14 Days Pretomanid 200 mg plus linezolid 600 mg plus moxifloxacin 400 mg daily plus bedaquiline 400 PO daily, followed by For 24 Weeks Pretomanid 200 mg plus linezolid 600 mg plus moxifloxacin 400 mg daily, and Bedaquiline 200 mg PO three times per week Omit moxifloxacin if resistant to fluoroquinolones (AI). Duration 6–24 months (see Managing Drug-Resistant TB in the Mycobacterium tuberculosis section for discussion)	Confirmed Resistance to Rifamycin +/- Other Drugs Therapy should be individualized based on drug susceptibility results and clinical and microbiologic responses, to include ≥5 active drugs, and with close consultation with experienced specialists (BIII).
Pneumocystis Pneumonia (PCP)	People with HIV who develop PCP despite TMP-SMX prophylaxis can usually be treated with standard doses of TMP-SMX (BIII). Duration of PCP treatment: 21 days (AII) For Moderate to Severe PCP TMP-SMX: (TMP 15–‍20 mg/kg/day and SMX 75–‍100 mg/kg/day) IV given in divided doses every 6 or 8 hours (AI); may switch to PO formulations after clinical improvement (AI). For Mild to Moderate PCP TMP-SMX: (TMP 15–‍20 mg/kg/day and SMX 75–‍100 mg/kg/day) PO given in three divided doses (AI), or TMP-SMX: (160 mg/800 mg or DS) two tablets PO three times daily (AI) Secondary Prophylaxis, After Completion of PCP Treatment TMP-SMX DS: one tablet PO daily (AI), or TMP-SMX (80 mg/400 mg or SS): one tablet PO daily (AI)	For Moderate to Severe PCP Primaquine 30 mg (base) PO daily plus (clindamycin 600 mg IV every 6 hours or 900 mg IV every 8 hours) or (clindamycin 450 mg PO every 6 hours or 600 mg PO every 8 hours) (AI) (some clinicians prefer this option because it is more effective and less toxic than pentamidine), or Pentamidine 4 mg/kg IV daily infused over ≥60 minutes (AI); can reduce dose to 3 mg/kg IV daily in the event of toxicities (BI) For Mild to Moderate PCP Dapsone 100 mg PO daily plus TMP 15 mg/kg/day PO given in three divided doses (BI), or Primaquine 30 mg (base) PO daily plus (clindamycin 450 mg PO every 6 hours or 600 mg PO every 8 hours) (BI), or Atovaquone 750 mg PO twice daily with food (BI) Secondary Prophylaxis, After Completion of PCP Treatment The following regimens can be used for people who are seropositive or seronegative for Toxoplasma gondii: TMP-SMX DS: one tablet PO three times weekly (BI), or Dapsone 50 mg PO daily with pyrimethamine^b 50 mg plus leucovorin 25 mg PO weekly (BI), or Dapsone 200 mg plus pyrimethamine^b 75 mg plus leucovorin 25 mg PO weekly (BI), or Atovaquone 1,500 mg PO daily with food (BI) The following regimens should only be used if the person is seronegative for Toxoplasma gondii: Dapsone 100 mg PO daily (BI), or Aerosolized pentamidine 300 mg monthly via Respirgard II nebulizer (BI), or Intravenous pentamidine 300 mg every 28 days (CIII)	Indications for Adjunctive Corticosteroids for Moderate to Severe PCP (AI) PaO₂<70 mmHg at room air, or A-a gradient ≥35 mmHg Prednisone Doses (Beginning as Early as Possible and Within 72 Hours of PCP Therapy) (AI) Days 1–5: 40 mg PO twice daily Days 6–10: 40 mg PO daily Days 11–21: 20 mg PO daily IV methylprednisolone can be administered as 80% of prednisone dose. Benefit of using a corticosteroid if started after 72 hours of treatment is unknown, but some clinicians will use it for moderate to severe PCP (BIII). Whenever possible, patients should be tested for G6PD before use of dapsone or primaquine. Alternative therapy should be used in patients found to have G6PD deficiency. Patients who are receiving pyrimethamine^b/sulfadiazine for the treatment or suppression of toxoplasmosis do not require additional PCP prophylaxis (AII). If TMP-SMX is discontinued because of a mild adverse reaction, re‍institution should be considered after the reaction resolves (AII). The dose can be increased gradually (desensitization) (BI) or the drug can be given at a reduced dose or frequency (CIII). TMP-SMX should be permanently discontinued in patients with possible or definite Stevens-Johnson syndrome or toxic epidermal necrosis (AIII). See alternative options.
Progressive Multifocal Leukoencephalopathy (PML)/JC Virus Infections	There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV. Initiate ART immediately in ART-naive patients (AII). Optimize ART to achieve viral suppression in patients who develop PML and receive ART but remain viremic (AIII).	None	Corticosteroids may be used for PML-IRIS (BIII). The optimal corticosteroid regimen has not been established but should be tailored to individual patients. ART should not be discontinued during PML-IRIS (AIII).
Syphilis (Treponema pallidum Infection)	Early-Stage (Primary, Secondary, and Early-Latent Syphilis) Benzathine penicillin G 2.4 million units IM for one dose (AII) Late-Latent Disease (>1 Year) or of Unknown Duration Benzathine penicillin G 2.4 million units IM weekly for three doses (AII) Late-Stage (Tertiary–Cardiovascular or Gummatous Disease) Benzathine penicillin G 2.4 million units IM weekly for three doses (AII) Note: Rule out neurosyphilis before initiation of benzathine penicillin. Persons with CSF abnormalities should be treated with a regimen for neurosyphilis [AII].) Neurosyphilis, Otic, or Ocular Syphilis Aqueous crystalline penicillin G 18–24 million units per day (administered as 3–4 million units IV every 4 hours or by continuous IV infusion) for 10–14 days (AII) +/- benzathine penicillin G 2.4 million units IM x 1 dose after completion of IV therapy (CIII)	Early-Stage (Primary, Secondary, and Early-Latent Syphilis) For Penicillin-Allergic Patients Doxycycline 100 mg PO twice daily for 14 days (BII), or Ceftriaxone 1 g IM or IV daily for 10–14 days (BII) Late-Latent Disease (>1 Year) or of Unknown Duration For Penicillin-Allergic patients Doxycycline 100 mg PO twice a day for 28 days (BIII) Neurosyphilis Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg PO four times a day for 10–‍14 days (BII) or For penicillin-allergic patients, desensitization to penicillin is the preferred approach (BIII); if not feasible and the patient is not pregnant, ceftriaxone 2 g IV daily for 10–‍14 days (BII).	The efficacy of non-penicillin alternatives has not been evaluated in patients with HIV, and they should be used only with close clinical and serologic monitoring. People with penicillin allergy whose compliance or follow-up cannot be ensured should be desensitized and treated with benzathine penicillin (AII). For management of early syphilis during pregnancy, limited evidence indicates a second dose of benzathine penicillin G 2.4 million units IM one week after the single dose treatment may be of benefit for congenital syphilis prevention (BII). The Jarisch-Herxheimer reaction is an acute febrile reaction accompanied by headache and myalgia that can occur within the first 24 hours after therapy for syphilis. This reaction occurs most frequently in patients with early syphilis, high non-treponemal titers, and prior penicillin treatment. Procaine penicillin has been discontinued by the manufacturer as of June 13, 2023 (see FDA Drug Shortages).
Talaromycosis (Penicilliosis)	Induction Therapy Liposomal amphotericin B 3–‍5 mg/kg/day IV (AIII) Duration 2 weeks (AIII), followed by consolidation therapy Consolidation Therapy Itraconazole 200 mg PO every 12 hours for 10 weeks (AI), followed by chronic maintenance therapy Chronic Maintenance Therapy Itraconazole 200 mg PO once daily (AI)	Induction Therapy Amphotericin B deoxycholate 0.7 mg/kg/day IV (if liposomal amphotericin B is not available) (AI) Duration 2 weeks (AI), followed by consolidation therapy If Amphotericin B Is Not Available, Contraindicated, or Not Tolerated Voriconazole 6 mg/kg IV every 12 hours on Day 1 (loading dose), then 4 mg/kg IV every 12 hours (BII), or Voriconazole 600 mg PO every 12 hours on Day 1 (loading dose), then 400 mg PO every 12 hours (BII) Duration: 2 weeks (BII), followed by consolidation therapy with itraconazole (preferred) or voriconazole Consolidation Therapy Voriconazole 200 mg PO every 12 hours for 10 weeks (BII), followed by chronic maintenance therapy Chronic Maintenance Therapy Itraconazole should be used (AI). Optimal dose of voriconazole for maintenance therapy has not been studied.	Itraconazole is not recommended as induction therapy for talaromycosis (AI). ART should be initiated as early as 1 week after initiation of treatment for talaromycosis (AII). Itraconazole and voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bidirectional. Refer to Drug–Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines for dosage recommendations. Itraconazole and voriconazole concentrations should be monitored beginning at 5 days and dose adjusted as needed to obtain serum trough concentrations for itraconazole should be >0.5 µg/mL (for a combined itraconazole plus hydroxyitraconazole level) and >1 µg/mL for voriconazole (BIII). Itraconazole solution is generally preferred over the capsule formulation because of improved bioavailability.
Toxoplasma gondii Encephalitis	Treatment of Acute Infection Pyrimethamine^b 200 mg PO one time, followed by weight-based therapy (AI): If ≤60 kg: Pyrimethamine^b 50 mg PO once daily plus sulfadiazine 1,000 mg PO every 6 hours plus leucovorin 10–25 mg PO once daily If >60 kg: Pyrimethamine^b 75 mg PO once daily plus sulfadiazine 1,500 mg PO every 6 hours plus leucovorin 10–‍25 mg PO once daily Note: Leucovorin dose can be increased to 50 mg daily or twice a day. TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg) IV or PO twice a day (AII) Duration for Acute Therapy At least 6 weeks (BII); longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks After completion of acute therapy, all patients should be initiated on chronic maintenance therapy. Chronic Maintenance Therapy Pyrimethamine^b 25–50 mg PO daily plus sulfadiazine 2,000–‍‍4,000 mg PO daily (in 2–‍4 divided doses) plus leucovorin 10–25 mg PO daily (AI), or TMP-SMX DS one tablet twice a day (AII)	Treatment of Acute Infection Pyrimethamine^b (leucovorin)* plus clindamycin 600 mg IV or PO every 6 hours (AI), or Atovaquone 1,500 mg PO twice a day with food plus pyrimethamine^b(leucovorin)* (BII), or Atovaquone 1,500 mg PO twice a day with food plus sulfadiazine 1,000–1,500 mg PO every 6 hours (weight-based dosing, as in preferred therapy) (BII), or Atovaquone 1,500 mg PO twice a day with food (BII) Chronic Maintenance Therapy (Pyrimethamine^b 25–‍50 mg plus leucovorin 10–‍25 mg) PO daily plus clindamycin 600 mg PO every 8 hours plus (BI), or Atovaquone 750–‍1,500 mg PO twice a day plus (pyrimethamine^b 25 mg plus leucovorin 10 mg) PO daily (BII), or Atovaquone 750–‍1,500 mg PO twice a day plus sulfadiazine 2,000–‍4,000 mg PO daily (in two to four divided doses) (BII), or Atovaquone 750–‍1,500 mg PO twice a day with food (BII) * Pyrimethamine^b and leucovorin doses are the same as for preferred therapy.	If pyrimethamine is unavailable or there is a delay in obtaining it, TMP-SMX should be used in place of pyrimethamine-sulfadiazine (AII). For patients with a history of sulfa allergy, sulfa desensitization should be attempted using one of several published strategies (BI). Atovaquone should be administered until therapeutic doses of TMP-SMX are achieved (CIII). Adjunctive corticosteroids (e.g., dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema (BIII); discontinue as soon as clinically feasible. Antiseizure medications should be administered to patients with a history of seizures (AII) and continued through acute treatment (BII) but should not be used as seizure prophylaxis (BII). If clindamycin is used in place of sulfadiazine, additional therapy must be added to prevent PCP (AII).
Varicella Zoster Virus (VZV) Disease	Primary Varicella Infection (Chickenpox) Uncomplicated Cases Initiate as soon as possible after lesion onset and continue for 5–‍7 days: Valacyclovir 1 g PO three times a day (AII), or Famciclovir 500 mg PO three times a day (AII) Severe or Complicated Cases Acyclovir 10 mg/kg IV every 8 hours for 7–‍10 days (AIII) May switch to oral valacyclovir, famciclovir, or acyclovir after defervescence and clinical improvement if no evidence of visceral involvement (BIII). Herpes Zoster (Shingles) Initiate therapy as soon as possible and within 1 week of rash onset, or any time prior to full crusting of lesions (AIII). Acute, Localized, Dermatomal For 7–10 days. Consider longer duration if lesions are slow to resolve (CIII). Valacyclovir 1 g PO three times a day (AII), or Famciclovir 500 PO mg three times a day (AII) Extensive Cutaneous Lesion or Visceral Involvement Acyclovir 10 mg/kg IV every 8 hours until clinical improvement is evident (AII) May switch to PO therapy (valacyclovir, famciclovir, or acyclovir) after clinical improvement (i.e., when no new vesicle formation and improvement of signs and symptoms of visceral VZV) to complete a total 10- to 14-day course (BIII). Herpes Zoster Ophthalmicus Late Dendriform Lesions of the Corneal Epithelium Oral antiviral treatment as stated above for “Acute, Localized, Dermatomal” herpes zoster, followed by suppressive therapy. If/when patient is not receiving oral antivirals, topical antivirals should be administered until resolution of lesions (AIII). Trifluridine 1% eye drops: see mpox for dosing (BIII) Ganciclovir 0.15% gel: see HSV for dosing (BIII) Stromal Keratitis and Anterior Uveitis Oral antiviral treatment as stated above for “Acute, Localized, Dermatomal” herpes zoster, followed by suppressive therapy. Alongside initial systemic antiviral treatment, topical corticosteroids should be administered (AII). Typical regimen using prednisolone acetate 1% drops: 1 drop in affected eye every 2 hours while awake (maximum eight times daily) until clinical response, then slow taper over many weeks if clinical improvement continues, eventually decreasing to 1–2 drops daily for at least 1 year (AII). Suppressive Therapy Valacyclovir 1 g PO daily for 12 months to prevent development of new, or exacerbations of existing, keratitis lesions and uveitis (AII). ARN Initial Therapy Acyclovir 10 mg/kg IV every 8 hours for 10–14 days or until lesion healing (AIII), followed by suppressive therapy. A single adjunctive intravitreal injection of ganciclovir (2 mg/0.05 mL) can also be given as a part of induction treatment (BIII). Additional injections can be given if there is a concern for lack of treatment response, but injections should not be given more frequently than twice weekly (BIII). Suppressive Therapy Valacyclovir 1 g PO daily (AIII) for ≥6 months PORN Optimal antiviral therapy and duration of therapy remains undefined and should be managed by an ophthalmologist experienced in the management of VZV ocular disease (AIII). Acyclovir 10 mg/kg IV every 8 hours or ganciclovir 5 mg/kg IV every 12 hours (AIII), plus Intravitreal ganciclovir 2 mg/0.05 mL or intravitreal foscarnet 1.2 mg/0.05 mL weekly (BIII)	Primary Varicella Infection (Chickenpox) Uncomplicated Cases Initiate as soon as possible after lesion onset and continue for 5–7 days: Acyclovir 800 mg PO five times a day (BII) Herpes Zoster (Shingles) Initiate therapy as soon as possible and within 1 week of rash onset, or any time prior to full crusting of lesions (AIII). Acute, Localized, Dermatomal For 7–10 days. Consider longer duration if lesions are slow to resolve (CIII). Acyclovir 800 mg PO five times a day (BII) ARN Suppressive Therapy Following initial therapy, acyclovir 800 mg PO twice daily (CIII) for ≥6 months	Consultation with an ophthalmologist experienced in the management of patients with VZV ocular disease is strongly recommended (AIII). People with V1 herpes zoster should have an ophthalmologic exam; patients with normal eye examinations initially should receive follow-up eye examinations, even after the skin lesions heal (AIII). All people with HIV should receive ART as soon as possible after diagnosis of HIV infection (AIII). The presence of disease caused by VZV is not an indication to defer or discontinue ART.
^a TAF 10-mg dose is in the FDC tablets of EVG/c/TAF/FTC and DRV/c/TAF/FTC; when TAF is used with other antiretrovirals, the dose is 25 mg. ^b Refer to Daraprim Direct for information on accessing pyrimethamine. ^cThis regimen was not studied and is not recommended for people who are pregnant, breastfeeding, <40 kg, or who have most types of extrapulmonary TB (other than pleural TB or lymphadenitis). ^dMany patients with RIF resistance also have resistance to isoniazid. Susceptibility should be confirmed in any patient with RIF resistance to determine if isoniazid can be included in the treatment regimen. ^eGiven the risk of ototoxicity and nephrotoxicity with aminoglycosides, use of amikacin should generally be restricted to bridging regimens, while awaiting availability of less toxic medications and/or results of drug-susceptibility testing. For information regarding the evidence ratings, refer to the Rating System for Prevention and Treatment Recommendations in the Introduction section of the Adult and Adolescent Opportunistic Infection Guidelines. Key: +/- = with or without; 3TC = lamivudine; A-a = alveolar-arterial; AASLD = American Association for the Study of Liver Diseases; ACTG = AIDS Clinical Trials Group; ARN = acute retinal necrosis; ART = antiretroviral therapy; ARV = antiretroviral; CD4 = CD4 T lymphocyte; CDC = Centers for Disease Control and Prevention; CDI = Clostridium difficile infection; CFU = colony-forming unit; CNS = central nervous system; CrCl = creatinine clearance; CSF = cerebrospinal fluid; DAA = direct-acting antiviral; DOT = directly observed therapy; DLBCL = diffuse large B-cell lymphoma; DRV = darunavir; DS = double strength; EMB = ethambutol; EPOCH = etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin combination therapy; EVG = elvitegravir; FDA = U.S. Food and Drug Administration; FDC = fixed-dose combination; FMT = fecal microbiota therapy; FTC = emtricitabine; G6PD = glucose-6-phosphate dehydrogenase; GI = gastrointestinal; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HD = hemodialysis; HHV-‍8 = human herpesvirus 8; HSV = herpes simplex virus; IDSA = Infectious Diseases Society of America; IM = intramuscular; IND = investigational new drug; INH = isoniazid; IRIS = immune reconstitution inflammatory syndrome; IRU = immune recovery uveitis; IV = intravenous; KS = Kaposi sarcoma; KSHV = Kaposi sarcoma–associated herpesvirus; LFA = lateral flow assay; LP = lumbar puncture; MCD = multicentric Castleman’s disease; MIC = minimum inhibitory concentration; MSM = men who have sex with men; NSAID = nonsteroidal anti-‍inflammatory drugs; OI = opportunistic infection; PaO₂ = partial pressure of oxygen; PCP = Pneumocystis pneumonia; PEL = primary effusion lymphoma; PO = oral; PORN = progressive outer retinal necrosis; PZA = pyrazinamide; RFB = rifabutin; RIF = rifampin; RPT = rifapentine; SMX = sulfamethoxazole; SS = single strength; SVR = sustained virologic response; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate; TMP = trimethoprim; VIGIV = vaccinia immune globulin intravenous; VZV = varicella zoster virus; WHO = World Health Organization

Opportunistic Infection

Preferred Therapy

Alternative Therapy

Other Comments

Bacterial Enteric Infections

Empiric Therapy Pending Definitive Diagnosis

For People With HIV and CD4 Count >500 Cells/mm³, 1–2 Days of Loose Stool Without Fever or Blood in Stool

Oral hydration, no further workup, and no antibiotics

For People With HIV and CD4 Count 200–500 Cells/mm³ With Diarrhea Severe Enough to Compromise Quality of Life or the Ability to Work

Azithromycin 500 mg PO daily for 5 days (BIII), or
Ciprofloxacin 500–750 mg PO every 12 hours for 5 days (BIII)

For People With HIV and Severe Disease (e.g., CD4 Count <200 Cells/mm³ or Concomitant AIDS-Defining Illness and With Clinically Severe Diarrhea [≥6 Liquid Stools Per Day or Bloody Stool and/or Accompanying Fever or Chills])

Hospitalization for diagnostic evaluation and IV antibiotics
Ceftriaxone IV 1–2 g every 24 hours (BIII)

Note: If Campylobacter or Shigella bacteremia is suspected, a carbapenem is preferred (BIII).

Therapy and duration should be adjusted based on microbiology and antibiotic sensitivity results.

If no pathogen is identified and the patient recovers quickly, 5 days of therapy is recommended.

For patients with persistent diarrhea (>14 days) without severe clinical signs, antibiotics therapy can be withheld until a diagnosis is made.

Diagnostic fecal specimens should be obtained before initiation of empiric antimicrobial therapy.

If a pathogen is identified, antibiotic susceptibilities should be performed to confirm and inform antibiotic choices, given increased reports of antibiotic resistance.

Oral or IV rehydration (if indicated) should be given to patients with diarrhea (AIII).

Antimotility agents should be avoided if there is concern about inflammatory diarrhea, including CDI (BIII).

Risk of bacteremia increases with decreasing CD4 count.

If no clinical response is observed after 3‍–‍4 days, consider a follow-up stool culture with antibiotic susceptibility testing or alternative diagnostic tests (e.g., toxin assays, molecular testing) to evaluate alternative diagnoses, antibiotic resistance, or drug–drug interaction (BIII).

MSM may be at increased risk for antibiotic-resistant enteric infections.

Campylobacteriosis

For Mild Disease If CD4 Count >200 Cells/mm³

No therapy unless symptoms persist for more than several days (CIII)

For Mild to Moderate Disease (If Susceptible)

Azithromycin 500 mg PO daily for 5 days (BIII) (not recommended for patients with bacteremia [AIII]), or
Ciprofloxacin 500–‍750 mg PO (or 400 mg IV) every 12 hours for 7‍–‍10 days (BIII)

For Campylobacter Bacteremia

Ciprofloxacin 500–750 mg PO (or 400 mg IV) every 12 hours for ≥14 days if the isolate is sensitive (BIII) plus an aminoglycoside (BIII) to limit the emergence of antibiotic resistance

For Recurrent Infections

Duration of therapy may be extended to 2–‍6 weeks (BIII).

For Mild to Moderate Disease (If Susceptible)

Levofloxacin 750 mg (PO or IV) every 24 hours (BIII)
Add an aminoglycoside to fluoroquinolone in bacteremic patients (BIII) to limit the emergence of antibiotic resistance.

Oral or IV rehydration if indicated (AIII)

Antimotility agents should be avoided (BIII).

Third-generation cephalosporins are not reliably active, and use of alternative cell wall–active agents, such as carbapenems, may be necessary in severely ill people who require empiric IV therapy until antimicrobial susceptibilities return.

In the United States in 2018, 29% of C. jejuni isolates were resistant to ciprofloxacin and 2% were resistant to azithromycin; among C. coli isolates, 40.5% were resistant to fluoroquinolone and 13.3% were resistant to azithromycin.

Effective ART may reduce the frequency, severity, and recurrence of Campylobacter infections.

Clostridium difficile Infection (CDI)

For Severe or Nonsevere CDI

Fidaxomicin 200 mg PO twice daily for 10 days (AI)

For Recurrent CDI

2021 IDSA CDI Guidelines suggest use of fidaxomicin over oral vancomycin because it has a greater likelihood for a sustained clinical response at 30 days (AI).

For Severe or Nonsevere CDI

Vancomycin 125 mg PO four times daily for 10 days (AI)

For Nonsevere CDI

If Neither Fidaxomicin nor Vancomycin Is Available

Metronidazole 500 mg (PO) three times daily for 10 days (CI)

Recurrent CDI

Vancomycin is an acceptable option (see IDSA Guideline for tapered and pulsed regimens) (AI).
FMT may be considered after three CDI episodes (i.e., an initial and two recurrent episodes) (CIII)

Severe CDI: white blood cell count ≥15,000 cells/mL or serum creatinine concentrations >1.5 mg/dL; nonsevere CDI: white blood cell count <15,000 cells/mL and serum creatinine concentrations <1.5 mg/dL

Salmonellosis

All people with HIV and salmonellosis should receive antimicrobial treatment due to an increase of bacteremia (by 20-fold to 100-fold) and mortality (by up to sevenfold) compared with individuals without HIV (AIII).

Oral or IV rehydration if indicated (AIII)

Antimotility agents should be avoided (BIII).

The role of long-term secondary prophylaxis in patients with recurrent Salmonella bacteremia is not well established. Must weigh the benefits against the risks of long-term antibiotic exposure (BIII).

Effective ART may reduce the frequency, severity, and recurrence of salmonella infections.

For Invasive Disease (Suspected or Confirmed)

Ceftriaxone IV 1–2 g every 24 hours pending susceptibilities (BIII)

For Nontyphoidal Salmonella Gastroenteritis (With or Without Bacteremia) (If Susceptible)

Ciprofloxacin 500–750 mg PO (or 400 mg IV) every 12 hours (AIII)

Duration of Therapy

For Gastroenteritis Without Bacteremia

If CD4 count ≥200 cells/mm³: 7–‍14 days (BIII)
If CD4 count <200 cells/mm³: minimum of 2 weeks (may extend to up to 6 weeks if with severe disease) (BIII)

For Gastroenteritis With Bacteremia

If CD4 count ≥200/mm³: 14 days or longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present) (BIII)
If CD4 count <200 cells/mm³: 2–‍6 weeks (BIII)

Secondary Prophylaxis Should Be Considered For Patients With—

Recurrent Salmonella bacteremia (BIII), or
Recurrent gastroenteritis (with or without bacteremia) with CD4 count <200 cells/mm³ with severe diarrhea (BIII)

For Nontyphoidal Salmonella Gastroenteritis (With or Without Bacteremia) (If Susceptible)

Levofloxacin 750 mg (PO or IV) every 24 hours (BIII), or
Moxifloxacin 400 mg (PO or IV) every 24 hours (BIII), or
TMP-SMX (160 mg/‌800 mg) PO (or IV) every 12 hours (BIII), or
Ceftriaxone 1–2 g IV every 24 hours (BIII)

Shigellosis

Ciprofloxacin 500–750 mg PO (or 400 mg IV) every 12 hours (if MIC <0.12 µg/mL) (AIII)

Duration of Therapy

Gastroenteritis: 5–7 days (AIII) (except ciprofloxacin [5–‍10 days] and azithromycin [5 days])
Bacteremia: ≥14 days (BIII)
Recurrent infections: Up to 6 weeks (BIII)

In Severely Ill Patients Requiring Empiric Parenteral Therapy While Awaiting Susceptibility

Consider initiating a carbapenem until antimicrobial susceptibilities are available (BIII).

Note: Increased resistance of Shigella to fluoroquinolones in the United States. Alternative antibiotics should be considered if ciprofloxacin MIC is ≥0.12 µg/mL (BIII).

Levofloxacin 750 mg (PO or IV) every 24 hours (BIII), or
Trimethoprim 160 mg/sulfamethoxazole 800 mg PO or IV every 12 hours for 5–‍7 days (BIII), or
Azithromycin 500 mg PO daily for 5 days (BIII), or
Ceftriaxone 1–2 g IV every 24 hours (BIII)

Note: Azithromycin and TMP-SMX are not recommended for treatment of bacteremia.

Note: Azithromycin-resistant Shigella spp. have been reported in MSM with HIV.

Therapy may slightly shorten the duration of illness and/or prevent the spread of infection (AIII).

Oral or IV rehydration if indicated (AIII)

Antimotility agents should be avoided (BIII).

Many Shigella strains that are resistant to fluoroquinolones exhibit resistance to other commonly used antibiotics. Antibiotic sensitivity testing of Shigella isolates from individuals with HIV should be performed routinely.

Given increasing antimicrobial resistance and limited data showing that antibiotic therapy limits transmission, antibiotic treatment may be withheld in patients with CD4 count >500 cells/mm³ whose diarrhea resolves prior to culture confirmation of Shigella infection (CIII).

Effective ART may decrease the risk of recurrence of Shigella infections.

Bartonellosis

For Bacillary Angiomatosis, Peliosis Hepatis, Bacteremia, and Osteomyelitis

Doxycycline 100 mg PO or IV every 12 hours (AII), or
Erythromycin 500 mg PO or IV every 6 hours (AII)

CNS Infections

(Doxycycline 100 mg +/- RIF 300 mg) PO or IV every 12 hours (AIII)

Confirmed Bartonella Endocarditis

(Doxycycline 100 mg IV plus RIF 300 mg PO or IV) every 12 hours for 6 weeks, then continue with doxycycline 100 mg IV or PO every 12 hours (BII)

Other Severe Infections

(Doxycycline 100 mg PO or IV +/- RIF 300 mg PO or IV) every 12 hours (BIII), or
(Erythromycin 500 mg PO or IV every 6 hours) +/- RIF 300 mg PO or IV every 12 hours (BIII)

Duration of Therapy

At least 3 months (AII)

For Bacillary Angiomatosis, Peliosis Hepatis, Bacteremia, Osteomyelitis, and Other Severe Infection

Azithromycin 500 mg PO daily (BIII)
Clarithromycin 500 mg PO twice a day (BIII)

Confirmed Bartonella Endocarditis

(Doxycycline 100 mg IV every 12 hours plus gentamicin 1 mg/kg IV every 8 hours) for 2 weeks, then continue with doxycycline 100 mg IV or PO every 12 hours (BII)

When RIF is used, take into consideration the potential for significant interaction with ARV drugs and other medications (see Table 4 for dosing recommendations).

If relapse occurs after initial (>3 month) course of therapy, long-term suppression with doxycycline or a macrolide is recommended as long as the CD4 count is <200 cells/mm³ (AIII).

Candidiasis (Mucocutaneous)

For Oropharyngeal Candidiasis—Initial Episodes (For 7–14 Days)

Fluconazole 200 mg PO loading dose, followed by 100–200 mg PO daily (AI)

For Esophageal Candidiasis (For 14–‍21 Days)

Fluconazole 200-mg loading dose, followed by 100–200 mg (up to 400 mg) PO or IV daily (AI). (Consider oral suspension for people with difficulty swallowing.)

For Uncomplicated Vulvovaginal Candidiasis

Fluconazole 150 mg PO for one dose (AII), or
Topical azoles (clotrimazole, butoconazole, miconazole, tioconazole, or terconazole) for 3–‍7 days (AII), or
Ibrexafungerp 300 mg PO twice daily for 1 day (BI)

For Severe or Recurrent Vulvovaginal Candidiasis

Fluconazole 100–200 mg PO daily for ≥7 days (AII), or
Topical antifungal ≥7 days (AII)

For Recurrent Vulvovaginal Candidiasis Only (The following regimens include treatment for the acute episode plus treatment to reduce recurrence.)

Oteseconazole 600 mg PO at Day 1, 450 mg at Day 2, followed by once-weekly 150-‍mg dosing starting at Day 14 for 11 weeks (AI) (for those who are not of reproductive potential); or
Fluconazole 150 mg PO at Days 1, 4, and 7, followed by oteseconazole 150 mg PO daily at Days 14–20, followed by oteseconazole 150 mg once weekly starting at Day 28 for 11 weeks (Weeks 4–14) (AI) (for those who are not of reproductive potential); or
Fluconazole 150 mg PO every 72 hours for three doses, followed by ibrexafungerp 300 mg PO twice daily 1 day per month for 6 months (BI). (Use an effective form of contraception during treatment and for 4 days after the last dose.)

For Oropharyngeal Candidiasis—Initial Episodes (For 7–‍14 Days)

Oral Therapy

Itraconazole oral solution 200 mg PO daily (BI), or
Posaconazole oral suspension 400 mg PO twice a day for 1 day, then 400 mg daily (BI), or
Posaconazole tablet 300 mg PO twice a day for 1 day, then 300 mg daily (BI)

Topical Therapy

Miconazole mucoadhesive buccal 50-‍mg tablet once daily; apply to mucosal surface over the canine fossa once daily (do not swallow, chew, or crush tablet.) (BI), or
Clotrimazole troches 10 mg PO five times daily (BI), or
Nystatin suspension 4–‍6 mL four times a day (BII)

For Esophageal Candidiasis (For 14–‍21 Days)

Itraconazole oral solution 200 mg PO daily (AI), or
Isavuconazole 400 mg PO loading dose, followed by 100 mg PO daily (BI), or
Isavuconazole 400 mg PO once weekly (BI), or
Voriconazole 200 mg PO or IV twice a day (BI), or
Posaconazole oral suspension 400 mg PO twice a day for 1 day, then 400 mg daily (BI), or
Posaconazole tablet 300 mg PO twice a day for 1 day, then 300 mg daily (BI), or
Lipid formulation of amphotericin B 3–‍4 mg/kg IV daily (BI), or
Caspofungin 70 mg IV loading dose, followed by 50 mg IV daily (BI), or
Micafungin 150 mg IV daily (BI), or
Anidulafungin 100 mg IV once, then 50 mg IV daily (BI)

For Azole-Refractory Candida glabrata Vaginitis

Boric acid vaginal suppository 600 mg once daily for 14 days (BII)

Chronic or prolonged use of azoles may promote the development of resistance.

Systemic azoles may have significant drug–drug interactions with ARV drugs.

A higher relapse rate for esophageal candidiasis is seen with echinocandins use than with fluconazole.

Suppressive therapy is usually not recommended (CIII) unless patients have frequent or severe recurrences.

If the Decision Is to Use Suppressive Therapy

Oropharyngeal Candidiasis

Fluconazole 100 mg PO once daily or three times weekly (BI)

Esophageal Candidiasis

Fluconazole 100–‍200 mg PO daily (BI), or
Posaconazole oral suspension 400 mg PO twice a day (BII), or
Posaconazole tablet 300 mg PO daily (BII)

Vulvovaginal Candidiasis

Fluconazole 150 mg PO once weekly (BII), or
Oteseconazole 600 mg at Day 1 and 450 mg at Day 2 for treatment of the acute episode, followed by once-weekly 150-mg doses starting at Day 14 for 11 weeks (AI) (for those who are not of reproductive potential); or
Fluconazole 150 mg at Days 1, 4, and 7 for treatment of the acute episode, followed by oteseconazole 150 mg daily at Days 14–20, followed by oteseconazole 150 mg once weekly starting at Day 28 for 11 weeks (Weeks 4–14) (AI) (for those who are not of reproductive potential); or
Ibrexafungerp 300 mg twice daily 1 day per month for 6 months (BI). (Use an effective form of contraception during treatment and for 4 days after the last dose.)

Chagas Disease (American Trypanosomiasis)

For Acute or Reactivated Disease

Benznidazole 5–8 mg/kg/day PO in two divided doses for 60 days (BIII) (commercially available at https://www.benznidazoletablets.com/en; most experts recommend a daily maximum of 300 mg), or
Nifurtimox (Lampit) 8–10 mg/kg/day PO in three divided doses for 60 days (BIII) (commercially available through retail sources)

None

Treatment is effective in reducing parasitemia and preventing clinical symptoms or slowing disease progression; however, these drugs have limited efficacy in achieving parasitological cure.

Treatment is not recommended for patients with advanced chagasic cardiomyopathy.

Duration of therapy has not been studied in patients with HIV.

Initiation or optimization of ART is recommended for all people with HIV with concomitant Trypanosoma cruzi (AIII).

Coccidioidomycosis

Mild to Moderate Pulmonary Infection

Fluconazole 400 mg PO daily (AII), or
Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO twice a day (AII)
Duration of therapy: clinical response to 3–6 months of therapy, CD4 count ≥250 cells/mm³, and viral suppression on ART (AII)

Severe Pulmonary or Extrapulmonary Infection (Except Meningitis)

Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily (AII), or
Lipid formulation amphotericin B 3–‍5 mg/kg IV daily (AIII)
Continue until clinical improvement, then switch to an azole (fluconazole 400 mg PO daily or itraconazole 200 mg PO twice daily) (BIII). Therapy should be continued for at least 12 months and usually much longer, and should be continued in patients with HIV viremia or with CD4 count <250 cells/mm³ (BIII).

Meningeal Infections

Fluconazole 800–1,200 mg PO daily (AII)
Duration of therapy: lifelong (AII)

Mild to Moderate Pulmonary Infection

For Patients Who Failed to Respond to Fluconazole or Itraconazole

Voriconazole 400 mg PO twice daily on Day 1, then 200 mg PO twice a day (BIII)
Posaconazole delayed release tablet 300 mg PO twice a day on Day 1, then 300 mg PO once daily (BIII), or
Isavuconazole sulfate 372 mg PO every 8 hours for six doses, then 372 mg once daily (BIII)

Severe Pulmonary or Extrapulmonary Infection (Except Meningitis)

Some specialists will combine amphotericin B with a triazole (fluconazole or itraconazole, with itraconazole preferred for bone disease) as initial therapy and continue triazole once amphotericin B is stopped (CIII).

Meningeal Infections

Itraconazole 200 mg PO two or three times daily (BII), or
Voriconazole 200–‍400 mg PO twice daily (BIII), or
Posaconazole delayed release tablet 300 mg PO twice on Day 1, then 300 mg PO once daily (CIII), or
Isavuconazole sulfate 372 mg PO every 8 hours for six doses, then 372 mg once daily (CIII)
Intrathecal amphotericin B deoxycholate when triazole antifungals are ineffective (AIII)

Some patients with meningitis may develop hydrocephalus and require CSF shunting.

Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of patients with HIV after discontinuation of triazole therapy (AII).

See Table 4 for drug–drug interactions or triazole antifungal drugs and other drugs for treatment or prevention of OIs.

Itraconazole, posaconazole, and voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bidirectional. Refer to Drug–Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines for dosage recommendations.

Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.

Intrathecal amphotericin B should only be given in consultation with a specialist and administered by an individual with experience with the technique.

Community-Acquired Pneumonia (CAP)

Empiric antibiotic therapy should be initiated promptly for patients presenting with clinical and radiographic evidence consistent with bacterial pneumonia. The recommendations listed are suggested empiric therapy. The regimen should be modified as needed once microbiologic results are available (BIII). Providers must also consider the risk of opportunistic lung infections (e.g., PCP, TB), which may alter the empiric therapy.

Empiric Outpatient Therapy

A PO beta-lactam plus a PO macrolide (azithromycin or clarithromycin) (AII)

Preferred Beta-Lactams

High-dose amoxicillin or amoxicillin/clavulanate

Alternative Beta-Lactams

Cefpodoxime or cefuroxime, or
Levofloxacin 750 mg PO once daily (AII), or moxifloxacin 400 mg PO once daily (AII), especially for patients with penicillin allergies

Empiric Therapy for Hospitalized Patients With Nonsevere CAP

An IV beta-lactam plus a macrolide (azithromycin or clarithromycin) (AI)

Preferred Beta-Lactams

Ceftriaxone, cefotaxime, or ampicillin-sulbactam
Levofloxacin 750 mg IV once daily (AI), or moxifloxacin, 400 mg IV once daily (AI), especially for patients with penicillin allergies.

Empiric Therapy for Hospitalized Patients With Severe CAP

An IV beta-lactam plus IV azithromycin (AI), or
An IV beta-lactam plus (levofloxacin 750 mg IV once daily or moxifloxacin 400 mg IV once daily) (AI)

Preferred Beta-Lactams

Ceftriaxone, cefotaxime, or ampicillin-sulbactam

Empiric Therapy for Patients at Risk of Pseudomonas Pneumonia

An IV antipneumococcal, antipseudomonal beta-lactam plus (ciprofloxacin 400 mg IV every 8–‍12 hours or levofloxacin 750 mg IV once daily) (AI)

Preferred Beta-Lactams

Piperacillin-tazobactam, cefepime, imipenem, or meropenem

Empiric Therapy for Patients at Risk for Methicillin-Resistant Staphylococcus aureus Pneumonia

Add vancomycin IV or linezolid (IV or PO) to the baseline regimen (AII).
Addition of clindamycin to vancomycin (but not to linezolid) can be considered for severe necrotizing pneumonia to minimize bacterial toxin production (CII).

Empiric Outpatient Therapy

A PO beta-lactam plus PO doxycycline (CIII)

Preferred Beta-Lactams

High-dose amoxicillin or amoxicillin/clavulanate

Alternative Beta-Lactams

Cefpodoxime or cefuroxime

Empiric Therapy for Hospitalized Patients With Nonsevere CAP

An IV beta-lactam plus doxycycline (CIII)

Empiric Therapy for Hospitalized Patients With Severe CAP

For Penicillin-Allergic Patients

Aztreonam IV plus (levofloxacin 750 mg IV once daily or moxifloxacin 400 mg IV once daily) (BIII)

Empiric Therapy for Patients at Risk of Pseudomonas Pneumonia

An IV antipneumococcal, antipseudomonal beta-‍lactam plus an IV aminoglycoside plus azithromycin (BII), or
An IV antipneumococcal, antipseudomonal beta-‍lactam plus an aminoglycoside plus (levofloxacin 750 mg IV once daily or moxifloxacin 400 mg IV once daily) (BIII)

For Penicillin-Allergic Patients

Replace the beta-lactam with aztreonam (BIII).

Duration

For most patients, 5–‍7 days
Patients should be afebrile for 48–72 hours and clinically stable before stopping antibiotics.
Longer duration is often required if severe CAP or bacteremia is present, and particularly if due to S. pneumoniae or complicated S. aureus pneumonia.

Fluoroquinolones should be used with caution in patients in whom TB is suspected but is not being treated.

Empiric therapy with a macrolide alone is not routinely recommended, because of increasing pneumococcal resistance (up to 30%) (BIII).

Patients receiving a macrolide for MAC prophylaxis may have bacterial resistance to macrolide due to chronic exposure.

For patients begun on IV antibiotic therapy, switching to PO should be considered when they are clinically improved and able to tolerate oral medications.

Antibiotic chemoprophylaxis is generally not recommended because of the potential for developing drug resistance and drug toxicities (AI).

Cryptococcosis

For CNS and/or Disseminated Disease

Induction Therapy (For ≥2 Weeks, Followed by Consolidation Therapy)

In the United States and other settings where daily electrolytes and kidney function monitoring and electrolyte and IV fluid administration is possible—
- Liposomal amphotericin B 3–‍4 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day for 2 weeks (AII) (Note: Flucytosine dose should be adjusted in patients with renal dysfunction.)
In resource-limited settings, as recommended by WHO—
- Liposomal amphotericin B 10 mg/kg IV as a single dose on Day 1, followed by flucytosine 25 mg/kg four times a day plus fluconazole 1,200 mg daily for 2 weeks (AI)
If not improved clinically or remain clinically unstable, continue induction therapy until the CSF culture is confirmed to be negative (BIII).

Consolidation Therapy (for ≥8 weeks, Followed by Maintenance Therapy)

Fluconazole 800 mg PO daily (AI)
For clinically stable patients with negative CSF cultures and ART has been started, dose can be reduced to 400 mg PO daily (AII)
If CSF remains positive (but clinically stable) after 2 weeks of induction therapy, use one of the following two options for an additional 2 weeks before reducing the dose of fluconazole to 800 mg PO daily:
- Fluconazole 1,200 mg PO daily with flucytosine 25 mg/kg PO four times a day for 2 weeks (BIII)
- Fluconazole 1,200 mg PO daily for 2 weeks (BIII), or

Note: Duration of consolidation therapy should be at least 8 weeks from the time of negative CSF culture (AII).

Maintenance Therapy

Fluconazole 200 mg PO daily for ≥1 year from initiation of antifungal therapy (AI)

For Non-CNS Extrapulmonary (BIII) or Diffuse Pulmonary Disease (BIII) or People With Non-CNS Symptoms With Normal CSF and Serum CrAg ≥1:640 by LFA (or ≥1:160 by EIA or Latex Agglutination) (BII)

Treatment is the same as for CNS cryptococcosis.

For Non-CNS Focal Pulmonary Infiltrates (With Mild Symptoms)

Fluconazole 400 mg daily for 6 to 12 months (duration guided by symptom resolution) (BIII)

For Asymptomatic Antigenemia Without Meningitis and Serum CrAg <1:640 by LFA (or <1:160 by EIA or Latex Agglutination)

Fluconazole: 800–1,200 mg PO daily for 2 weeks, followed by 400–800 mg PO daily for a total of 10 weeks, then fluconazole 200 mg PO daily for a total of 6 months plus effective ART (BIII)

For CNS and/or Disseminated Disease

Induction Therapy (For ≥2 Weeks, Followed by Consolidation Therapy)

Amphotericin B lipid complex 5 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day for 2 weeks (BII), or
Amphotericin B deoxycholate 1 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day for 1 week, followed by fluconazole 1,200 mg PO daily for an additional week (BI)

Additional Studied Induction Regimens (For 2 Weeks)

Amphotericin B deoxycholate 0.7–‍0 mg/kg IV daily plus flucytosine 25 mg/kg PO four times a day (BI)
Liposomal amphotericin B 3–‍4 mg/kg IV daily plus fluconazole 800–‍1,200 mg PO daily (BIII)
Amphotericin B deoxycholate 0.7–‍0 mg/kg IV daily plus fluconazole 800–‍1,200 mg PO or IV daily (BI)
Fluconazole 1,200 mg PO or IV daily plus flucytosine 25 mg/kg PO four times a day (BII)

Consolidation Therapy (for ≥8 Weeks, Followed by Maintenance Therapy)

If fluconazole is not available or not well tolerated: Itraconazole 200 mg PO twice a day for 8 weeks (CI)

Maintenance Therapy

If fluconazole is not available or not well tolerated: Itraconazole 200 mg PO twice a day (CI)
If susceptibility studies have been performed and the fluconazole MIC is ≥16 µg/mL, the fluconazole dose may be increased to 400 mg daily (BIII).

Alternative treatment options are the same as for CNS cryptococcosis.

Addition of flucytosine to amphotericin B has been associated with more rapid sterilization of CSF and decreased risk for subsequent relapse.

Patients receiving flucytosine should have either blood levels monitored (peak level 2 hours after dose should be 25–‍100 µg/mL) or at least twice weekly monitoring of complete blood counts for cytopenia. Dosage should be adjusted in patients with renal insufficiency (BII).

Irrespective of which regimen is used, patients must be followed carefully in hospital for at least 7 days and ideally 14 days (AII). For patients with CNS disease, LP should be performed at Day 7 and Day 14 to ensure an appropriate clinical response and culture sterility. If increased ICP is documented, daily LP should be performed until the pressure is decreased into the normal range and symptoms have abated (AII).

Opening pressure should always be measured when an LP is performed. Repeated LPs or CSF shunting are essential to effectively managing increased intracranial pressure.

Corticosteroids and mannitol are ineffective in reducing ICP and are not recommended (AIII).

Some specialists recommend a brief course of tapering dose of corticosteroid for management of severe IRIS symptoms (BIII).

All people with non-CNS extrapulmonary symptoms and cryptococcal antigenemia should have their CSF sampled to rule out CNS disease.

People with asymptomatic cryptococcal antigenemia, lower risk, and serum CrAg titer <1:80 by LFA (or <1:20 by EIA or latex agglutination) can be safely treated without lumbar puncture (AI). All others with asymptomatic cryptococcal antigenemia should undergo CSF sampling to rule out CNS disease.

Cryptosporidiosis

Aggressive oral and/or IV rehydration and replacement of electrolyte loss (AIII), and
Symptomatic treatment of diarrhea with anti-motility agents (AIII), and
ART initiation to achieve immune restoration to CD4 count > 100 cells/mm³ (AII).

No therapy has been shown to be effective without ART. Consider a trial of these agents in conjunction with ART, rehydration, and symptomatic treatment:

Nitazoxanide 500–1,000 mg PO twice a day with food for at least 14 days (CIII), or
Paromomycin 500 mg PO four times daily for 14–21 days (CIII)

Tincture of opium may be more effective than loperamide in management of diarrhea (CIII).

Because diarrhea can cause lactase deficiency, patients should avoid milk products (CIII).

Cystoisosporiasis

For Acute Infection

TMP-SMX (160 mg/800 mg) PO (or IV) four times daily for 10 days (AII), or
TMP-SMX (160 mg/800 mg) PO (or IV) twice daily for 7 days (BI)
In patients with persistent or worsening symptoms while on twice-daily dosing, consider increasing the daily dose and/or the duration to 3–‍4 weeks (BIII).
IV TMP-SMX may be used for patients with potential or documented malabsorption.

Chronic Maintenance Therapy (Secondary Prophylaxis)

In People With CD4 Count <200 Cells/mm³

TMP-SMX (160 mg/800 mg) PO three times weekly (AI), or
TMP-SMX (160 mg/‌800 mg) PO daily (AIII)

For Acute Infection

Pyrimethamine^b 50–‍75 mg PO daily plus leucovorin 10–‍25 mg PO daily for 4 weeks (BIII), or
Ciprofloxacin 500 mg PO or 400 mg IV twice daily for 7 days (CI)

Chronic Maintenance Therapy (Secondary Prophylaxis)

In People With CD4 Count <200 Cells/mm³

TMP-SMX (320 mg/1,600 mg) three times weekly (BIII), or
Pyrimethamine^b 25 mg PO daily plus leucovorin 5–‍10 mg PO daily (BIII), or
Ciprofloxacin 500 mg three times weekly (CI) as a second-line alternative

Fluid and electrolyte management in patients with dehydration (AIII)

Nutritional supplementation for patients who are malnourished (AIII)

Immune reconstitution with ART may result in fewer relapses; therefore, ART initiation should not be deferred (AIII).

Cytomegalovirus (CMV) Disease

CMV Retinitis Induction Therapy (Followed by Maintenance Therapy)

Valganciclovir 900 mg PO every 12 hours for minimum 14–‍21 days, then maintenance therapy with valganciclovir 900 mg PO once daily (AI), or
Ganciclovir 5 mg/kg IV every 12 hours for minimum 14–‍21 days, then maintenance therapy with valganciclovir 900 mg PO once daily (AI), or
Ganciclovir 5 mg/kg IV every 12 hours for minimum 14–‍21 ‍‍days, then maintenance therapy with ganciclovir 5 mg/kg IV daily (AI)

Note: Many clinicians prefer the IV formulation when retinitis is more central and sight-threatening or when adequate GI absorption is a concern; transition to oral valganciclovir can be considered when there is evidence of clinical response.

CMV Retinitis—Immediate Sight-Threatening Lesions (Within 1,500 Microns of the Fovea or Optic Disc)

In addition to systemic therapy (as listed above): intravitreal injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection), repeated weekly during the induction period until lesion inactivity is achieved (BIII), followed by systemic treatment alone for maintenance therapy.

CMV Retinitis—Peripheral Lesions

Valganciclovir 900 mg PO every 12 hours for minimum 14–‍21 days, then maintenance therapy with valganciclovir 900 mg PO once daily (AI)

Duration of Maintenance Therapy

Continue maintenance therapy for at least 3 months, and lesions are inactive, and CD4 count ≥100 cells/mm³for at least 3 months in response to ART (AII)

CMV Esophagitis or Colitis

Ganciclovir 5 mg/kg IV every 12 hours (AI); may switch to valganciclovir 900 mg PO every 12 hours when the patient can absorb and tolerate oral therapy (AIII).
Valganciclovir 900 mg PO every 12 hours can be used in patients with mild disease (AIII).
Duration: 21–42 days or until signs and symptoms have resolved (AIII)

CMV Pneumonia

Ganciclovir 5 mg/kg IV every 12 hours (BIII)
Duration: ≥21 days or until signs and symptoms have resolved (CII)

CMV Neurological Disease

Ganciclovir 5 mg/kg IV every 12 hours plus foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours) (BIII).
Duration: ≥21 days based on clinical response (AIII)

CMV Retinitis Induction Therapy (Followed by Maintenance Therapy)

Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 14–21 days, then maintenance therapy with foscarnet 90 mg/kg or 120 mg/kg IV every 24 hours (BI), or
Cidofovir 5 mg/kg IV every week for 2 weeks, then maintenance therapy with cidofovir 5 mg/kg IV every other week. Administer 1 L of normal saline before and, if additional fluid load can be tolerated, administer another 1 L of normal saline after each cidofovir infusion. Administer probenecid 2 g PO 3 hours before each cidofovir dose followed by 1 g PO 2 hours after the dose, and 1 g PO 8 hours after the dose (total of 4 g) (CI).

CMV Retinitis—Immediate Sight-Threatening Lesions (Within 1,500 Microns of the Fovea or Optic Disc)

In addition to systemic therapy (as listed above): intravitreal therapy as listed in the Preferred section

CMV Esophagitis or Colitis

Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours (BIII)—for patients with treatment-limiting toxicities to ganciclovir or with ganciclovir resistance; or
Cidofovir (dosing as listed above) (CI)
Duration: 21–42 days or until signs and symptoms have resolved (AIII)

CMV Pneumonia

Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours (BIII)
Duration: ≥ 21 days or until signs and symptoms have resolved (CII)

CMV retinitis treatment should be individualized based on tolerance of systemic medications, prior exposure to anti-CMV drugs, and location of lesions as well as with the active participation of an ophthalmologist who is familiar with diagnosis and management of this retinal disease.

Systemic therapy must be administered to prevent disease in the contralateral eye until immune reconstitution has occurred.

After resolution of the acute non-ocular CMV disease and initiation of effective ART, chronic maintenance therapy is not routinely recommended for CMV GI disease, pneumonia, and central nervous system disease unless there is concurrent retinitis, there have already been recurrent infections, or severe disease was present initially

Ophthalmologic monitoring is recommended during treatment and after discontinuation of maintenance therapy and is continued after immune reconstitution. See text for ophthalmic monitoring recommendations and frequency of follow-up.

Initiate ART within 1–‍‎‍2 weeks after starting anti-CMV therapy for retinitis, esophagitis, colitis, or other end-organ diseases caused by CMV (BIII).

With neurologic disease, including CMV encephalitis, ventriculitis, and radiculitis, the Panel recommends initiating ART within 2 weeks, although clinical judgment based on individual cases is needed (BIII).

Immune recovery uveitis (IRU) may develop in the setting of immune reconstitution. See text for information on the treatment of IRU.

Cidofovir should be avoided in patients with sulfonamide allergy because of cross-hypersensitivity with probenecid.

For people with renal insufficiency, see Table 6 for information on dosing adjustments for valganciclovir, ganciclovir, foscarnet, and cidofovir.

Hepatitis B Virus (HBV) Disease

ART is recommended for all patients with HIV/HBV coinfection regardless of CD4 cell count and HBV DNA level (AII).

The ART regimen must include drugs that are active against both HBV and HIV (AII).

If CrCl ≥60 mL/min—

(TAF [10 or 25 mg]^a plus FTC 200 mg) or (TAF 25 mg plus 3TC 300 mg) PO once daily (AII), or
(TDF 300 mg plus [FTC 200 mg or 3TC 300 mg]) once daily (AII)

If CrCl 30–59 mL/min—

TAF (10 or 25 mg)^a plus FTC 200 mg PO once daily (AII)

If CrCl <30 mL/min, Not on HD—

Renally dosed entecavir (in place of TDF/[FTC or 3TC] or TAF/FTC) with a fully suppressive ART regimen (AIII), or
ART with renally dose-adjusted TDF and (FTC or 3TC) can be used (AIII) if recovery of renal function is unlikely.
If CrCl ≥15 to 29 mL/min, then ART with TAF (10 or 25 mg)^a once daily plus renally dose-adjusted FTC or 3TC is an option (AIII).
- Some clinicians may continue full-dose FTC or 3TC to allow for people to remain on fixed-dose TAF/FTC products.

If on HD—

Renally dose-adjusted TDF plus [FTC 200 mg or 3TC 300 mg once daily] (see Table 6) (AII)
TAF [10 or 25 mg]^a plus FTC 200 mg PO once daily (given after HD on dialysis days) (AII)

Duration

Continue treatment indefinitely (AIII).

For People on NRTI-Sparing ART

Entecavir 0.5 mg once daily may be used in place of (TAF or TDF) plus (3TC or FTC) (AIII).

Directly acting HBV drugs—such as emtricitabine, entecavir, lamivudine, and tenofovir—must not be given in the absence of a fully suppressive ART regimen to avoid selection of drug-resistant HIV (AI).

Chronic administration of 3TC or FTC as the only HBV-active drug should be avoided because of the high rate of selection of HBV drug-resistance mutations (AI).

People with 3TC-resistant HBV will have cross-resistance to FTC and partial resistance to entecavir, these agents should not be used (AI). If 3TC resistance is suspected or documented, TDF or TAF should be added to the ART regimen (AIII).

When changing ART regimens, continue agents with anti-HBV activity (AIII).

If anti-HBV therapy is discontinued and a flare occurs, therapy should be reinstituted because it can be potentially lifesaving (AIII).

Because HBV reactivation can occur during treatment for HCV with direct-acting antivirals in the absence of anti-HBV therapy, all people with HIV/HBV coinfection who will be treated for HCV infection should be on HBV-active ART at the time of HCV treatment initiation (AIII).

If immunosuppressive therapy is given, HBV reactivation can occur. For people who are HBsAg-positive, treatment for HBV infection should be administered (AII). For detailed recommendations, see Hepatitis B Virus Infection.

Hepatitis C Virus (HCV) Disease

For Treatment-Naive Patients Without Cirrhosis (Any Genotype or No Pre-Treatment Genotype)

Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AI), or
Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily for 12 weeks (AI)

Characteristics that exclude patients from receiving simplified approach to therapy are outlined in Box 1 of the Hepatitis C Virus section.

For Treatment-Naive Patients with Compensated Cirrhosis (Recommendations Based on Genotypes)

Genotypes 1, 2, 4–6

Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AIII), or
Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily for 12 weeks (AI)

Genotype 3

Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AIII)

For Treatment of Acute HCV Infection

Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 8 weeks (AII) or
Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily for 12 weeks (AII)

For Treatment-Naive Patients with Compensated Cirrhosis (Recommendations Based on Genotypes)

Genotypes 1, 2, 4–6

Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 12 weeks (CI)

Genotype 3

Glecaprevir/pibrentasvir FDC (100 mg/40 mg per tablet), three tablets daily for 12 weeks (CI) or
Sofosbuvir/velpatasvir FDC (400 mg/100 mg per tablet), one tablet daily with or without ribavirin for 12 weeks pending results of NS5A RAS testing (CI)

A simplified approach to HCV treatment can be used in treatment-naive patients with any genotype and without cirrhosis. This approach includes standardized treatment, with no on-treatment testing or in-person follow-up and limited follow-up to confirm SVR.

See the Hepatitis C Virus section to review a summary of drug–drug interactions between HCV therapy and ARV drugs.

HCV treatment should not be withheld solely due to perceived lack of adherence to ART or untreated HIV (BIII).

Effort should be made to document SVR (HCV RNA less than lower limits of quantification) at least 12 weeks after completion of therapy (AI). Patients without cirrhosis who achieve SVR do not require continued liver disease monitoring.

Recommendations for treatment after DAA failure are not provided. The reader is referred to the corresponding section in the AASLD/IDSA HCV treatment guidance.

Herpes Simplex Virus (HSV) Disease

Orolabial Lesions (For 5–‍10 Days)

Valacyclovir 1 g PO twice a day (AIII), or
Famciclovir 500 mg PO twice daily (AIII), or
Acyclovir 400 mg PO three times daily (AIII)

Initial Genital Lesions (For 7–‍10 Days) or Recurrent Genital Lesions (For 5–10 Days)

Valacyclovir 1 g PO twice daily (AI), or
Famciclovir 500 mg PO twice daily (AI), or
Acyclovir 400 mg PO three times daily (AI)

Severe Mucocutaneous and Visceral or Disseminated HSV

Initial therapy: Acyclovir 10 mg/kg IV every 8 hours for 10–14 days (AIII)
For mucocutaneous lesions, change to PO therapy (dose as above) once lesions begin to regress (AIII); continue PO therapy until lesions have completely healed (AIII).
Some clinicians will extend the course of treatment for visceral or disseminated disease based on clinical response and degree of immunosuppression.

Epithelial Keratitis

Valacyclovir 1 g PO twice daily for 5–10 days (BIII), or
Acyclovir 400 mg PO five times daily for 5–10 days (BIII), or
Trifluridine eye drops (BIII) (see mpox for dosing), or
Ganciclovir 0.15% gel: 1 drop into the affected eye five times a day (every 3 hours while awake) until re-epithelialization has occurred; then 1 drop three times a day for an additional 7 days (BIII)

Stromal Keratitis (For ≥1 Year)

Acyclovir 400 mg PO twice daily (AII) or valacyclovir 500 mg once daily (AIII), plus
Prednisolone 1%: 1 drop into the affected eye six to eight times per day for at least 10 weeks followed by taper; exact course should be managed by ophthalmologist and based on individual patient course (AIII).

HSV Meningitis (For 10–14 Days) (AIII)

Initial therapy: Acyclovir 10 mg/kg IV every 8 hours
After clinical improvement, change to valacyclovir 1 g PO three times a day

HSV Encephalitis (For 14–‍21 Days) (CIII)

Acyclovir 10 mg/kg IV every 8 hours
Some clinicians will elect to extend the course based on clinical response and degree of immunosuppression.

Chronic Suppressive Therapy

Valacyclovir 500 mg PO twice daily (AI)
May continue indefinitely, regardless of CD4 count; re-evaluate annually, particularly if immune reconstitution has occurred (BIII).

For Acyclovir-Resistant HSV (Based on Clinical Response, Typically for 21–28 Days or Longer)

Preferred Therapy

Foscarnet 40 mg/kg IV every 8–12 hours until clinical response (AI)

Alternative Therapy

Topical imiquimod 5% three times weekly (BIII), or
Topical cidofovir 1% once daily (BIII), or
Topical trifluridine 1% three times daily (BIII), or
Topical foscarnet 1% five times daily (BIII), or
IV cidofovir once weekly for 2 weeks, then every other week (CIII). See CMV Retinitis for information on concomitant probenecid and hydration.

Chronic Suppressive Therapy

Acyclovir 400 mg PO twice daily (AI), or
Famciclovir 500 mg PO twice daily (AI), or
Valacyclovir 500 or 1,000 mg PO once daily (CIII). See the Herpes Simplex Virus Disease section for additional information.
May continue indefinitely, regardless of CD4 count; re-evaluate annually, particularly if immune reconstitution has occurred (BIII).

HSV infection can be treated with episodic therapy when symptomatic lesions occur or with daily suppressive therapy to prevent recurrences.

For ophthalmic HSV disease, consultation with an ophthalmologist experienced with HSV ocular disease is strongly recommended (AIII).

Topical formulations of trifluridine, cidofovir, and foscarnet are not commercially available but can be extemporaneously compounded.

An expanded access program of oral pritelivir is available for immunocompromised patients with acyclovir-resistant HSV infection. See the AiCuris Pritelivir website.

Chronic suppressive therapy is indicated for people with severe or frequent recurrences of genital herpes (AI), for people who want to minimize frequency of recurrences (AI), and to reduce the risk of genital ulcer disease in people with CD4 counts <250 cells/mm³ who are starting ART (BI).

Recurrences following episodes of acyclovir-resistant HSV can be caused by either acyclovir-resistant or acyclovir-sensitive strains; after resolution of the acyclovir-resistant episode, suppressive therapy with acyclovir can be considered to prevent additional recurrences (CIII).

Histoplasmosis

Severe Disseminated Disease

Induction Therapy (For ≥2 Weeks or Until Clinically Improved)

Liposomal amphotericin B 3 mg/kg IV daily (AI)

Maintenance Therapy (For ≥12 Months)

Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO twice a day (AII)

Mild to Moderate Disseminated Disease or Acute Pulmonary Histoplasmosis in Persons With CD4 <300 Cells/mm³

Both Induction and Maintenance Therapy (For ≥12 Months)

Itraconazole 200 mg PO three times a day for 3 days, then 200 mg PO twice a day (AII)

Meningitis

Induction Therapy (4–6 Weeks Depending on Symptom Resolution and Improvement of CSF Findings)

Liposomal amphotericin B 5 mg/kg IV daily (AIII)

Maintenance Therapy (For ≥12 Months and Until Resolution of Abnormal CSF Findings)

Itraconazole 200 mg PO two to three times a day (AIII), with dose adjustment based on serum itraconazole concentration

Long-Term Suppression Therapy

For Patients with Severe Disseminated or CNS Infection After Completion of ≥12 Months of Therapy (AIII) or Who Relapse Despite Appropriate Therapy (after reinduction therapy) (BIII)

Itraconazole 200 mg PO daily (AIII)

Severe Disseminated Disease

Induction Therapy

Amphotericin B lipid complex 5 mg/kg IV daily (AIII)

Maintenance Therapy (For ≥12 Months)

Posaconazole extended-release tablet 300 mg PO twice a day for 1 day, then 300 mg PO once daily (BIII)
Voriconazole 400 mg PO twice a day for 1 day, then 200 mg PO twice a day (BIII), or
Fluconazole 800 mg PO daily (CII)

Mild to Moderate Disseminated Disease or Acute Pulmonary Histoplasmosis in People With CD4 Count <300 Cells/mm³

Both Induction and Maintenance Therapy (For ≥12 Months)

Posaconazole extended-release tabet 300 mg PO twice a day for 1 day, then 300 mg PO once daily (BIII)
Voriconazole 400 mg PO twice a day for 1 day, then 200 mg PO twice a day (BIII), or
Fluconazole 800 mg PO daily (CII)

Meningitis

Induction Therapy (4–6 Weeks Depending on Symptom Resolution and Improvement of CSF Findings)

Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily (BIII)

Maintenance Therapy (For ≥12 Months and Until Resolution of Abnormal CSF Findings)

Voriconazole 400 mg PO twice a day for 1 day, then 200 mg twice a day (BIII), or
For people who cannot tolerate itraconazole and voriconazole: Fluconazole 800 mg PO daily (CII)

Long-Term Suppression Therapy

Fluconazole 400 mg PO once daily (CII)
Voriconazole 200 mg PO twice daily (BIII)
Posaconazole 300 mg extended-release tablet PO once daily (BIII)

Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and ARV efficacy and reduce concentration-related toxicities.

Random serum concentration of itraconazole between 1–‍2 µg/mL is recommended. Frequency and severity of toxicities increase when concentration is ≥5 µg/mL.

The recommendations for posaconazole, voriconazole, and fluconazole are based on very limited clinical data and for people who are only moderately ill.

Human Herpesvirus-8 (HHV-8) Associated Diseases
(Kaposi Sarcoma [KS], Primary Effusion Lymphoma [PEL], Multicentric Castleman’s Disease [MCD])

ACTG Stage T0 (Localized Involvement of Skin and/or Lymph Nodes and/or Minimal Oral Disease Only)

ART (AII) alone, or
ART plus liposomal doxorubicin (AIII), if disease does not respond to ART alone

ACTG Stage T1 (Extensive and/or Symptomatic KS Skin Lesions, Extensive Oral Disease, Tumor-Associated Edema and/or Ulceration, or Any Visceral Involvement)

ART plus liposomal doxorubicin (AI)

MCD

MCD without KS: ART plus rituximab (BII)
MCD with KS: ART plus rituximab with liposomal doxorubicin (AII)

PEL or HHV-8 DLBCL (With or Without KS)

PEL or HHV-8-associated DLBCL: ART plus combination chemotherapy, such as EPOCH (AIII)
PEL or HHV-8-associated DLBCL with MCD: ART plus dose-adjusted EPOCH plus rituximab (CII)

KSHV-Associated Inflammatory Cytokine Syndrome

After excluding MCD and PEL, ART plus rituximab with combination chemotherapy for concurrent KS (CII)

ACTG Stage T1 (Extensive and/or Symptomatic KS Skin Lesions, Extensive Oral Disease, Tumor-Associated Edema and/or Ulceration, or Any Visceral Involvement)

ART plus paclitaxel, if liposomal doxorubicin is not available (AI), or to treat recurrence after treatment with liposomal doxorubicin (AII), or
ART with oral pomalidomide plus thromboprophylaxis (e.g., low-dose aspirin 81 mg daily) (BII)

MCD

ART plus IV ganciclovir (or oral valganciclovir) with or without high-dose zidovudine—not for use in cases of multi-organ failure, such as renal and/or hepatic failure (CII)

Treatment should be undertaken in consultation with both oncology and infectious disease specialists, with additional input from centers specifically caring for people with HIV and cancer (AIII).

All HHV-8–specific treatments should be given with ART (AI).

ART given concurrently with chemotherapy should be chosen to minimize drug–drug interactions and additive toxicities (AIII).

Systemic corticosteroids or other immunosuppressants in patients with KS should either be avoided or used under close observation, given the potential for exacerbation of KS (AIII).

Although corticosteroids appear to be effective as an adjunctive therapy for MCD, they should be used with caution or avoided, especially in patients with concurrent KS, given potential for exacerbation of life-threatening KS (AIII).

One-third of patients receiving rituximab may have subsequent exacerbations or emergence of KS.

Human Papillomavirus (HPV) Disease

Treatment of Genital Warts

Patients with HIV may have larger or more numerous warts and may not respond as well to therapy for genital warts when compared to individuals without HIV.

Intralesional interferon is usually not recommended because of high cost, difficult administration, and potential for systemic side effects (CIII).

In patients with HIV, the rate of recurrence of genital warts despite treatment is high.

There is no consensus on the treatment of oral warts. Many treatments for anogenital warts cannot be used in the oral mucosa. Surgery is the most common treatment for oral warts that interfere with function or for aesthetic reasons.

Patient-Applied Treatment Options for Uncomplicated External Warts That Can Be Easily Identified by Patients

Topical imiquimod 5% cream: Apply to genital warts at bedtime on three nonconsecutive nights per week for up to 16 weeks, until lesions are no longer visible. Each treatment should be washed with soap and water 6–‍10 hours after application (BII); or
Topical podophyllotoxin (e.g., podofilox 0.5% solution or 0.5% gel): Apply to genital warts twice a day for 3 days, followed by 4 days of no therapy. Can be repeated weekly for up to four cycles (BIII); or
Topical sinecatechins 15% ointment: Apply to affected areas three times a day for up to 16 weeks, until warts are completely cleared and not visible (BIII); or
Topical cidofovir 1%: Daily for 5 days per week for 8 weeks (CIII). Topical formulation is not commercially available but may be compounded.

Provider-Applied Therapy for Complex or Multicentric Lesions, or Lesions Inaccessible to Patient, or Due to Patient or Provider Preference

Cryotherapy (liquid nitrogen or cryoprobe): Apply until each lesion is thoroughly frozen. Repeat every 1–‍2 weeks for up to 4 weeks, until lesions are no longer visible (BIII). Some specialists allow the lesion to thaw, then freeze a second time in each session (BIII); or
Trichloroacetic acid or bichloroacetic acid cauterization (80–90% aqueous solution): Apply to warts only and allow to dry until a white frost develops. Repeat weekly for up to 6 weeks, until lesions are no longer visible (BIII); or
Intralesional cidofovir (15 mg/mL solution) injected directly into the wart (maximum 1 mL per session). May be repeated every 4 weeks for total of 3–‍4 treatments (CIII).
Surgical excision (BIII) or laser surgery (CIII) for external or anal warts

Leishmaniasis

Visceral

For Leishmania infantum/chagasi

Liposomal amphotericin B 3–‍5 mg/kg IV daily (AII), or
Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on Days 1–5, 10, 17, 24, 31, 38) (AII)
To achieve total dose of 20–‍60 mg/kg (AII)

For Leishmania donovani

Liposomal amphotericin B 5 mg/kg on Days 1, 3, 5, 7, 9, and 11 plus miltefosine 50 mg PO twice daily (for 28 days if from East Africa or 14 days if from Southeast Asia) (BI)

Chronic Maintenance Therapy

For Patients With CD4 Count <200 Cells/mm³ (AII)

Liposomal amphotericin B 4 mg/kg IV every 2–4 weeks (AII)

For Leishmania infantum/chagasi or donovani

Amphotericin B deoxycholate 0.5–‍0 mg/kg IV daily for total dose of 1.5–‍2.0 g (BII), or
Pentavalent antimony (meglumine antimoniate) 20 mg/kg IV or IM daily for 28 days (BII)

For Leishmania donovani

Liposomal amphotericin B 3–‍5 mg/kg IV daily to achieve total dose of 20–‍60 mg/kg (AII), or
Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on Days 1–‍5, 10, 17, 24, 31, 38) to achieve total dose of 20–‍60 mg/kg (AII), or
For Indian L. donovani: Miltefosine ~2.5–‍3.0 mg/kg PO daily in two or three divided doses (maximum 150 mg daily) for 28 days (BII)

Chronic Maintenance Therapy (Secondary Prophylaxis)

Amphotericin B lipid complex 3 mg/kg IV every 21 days (BII), or
Pentavalent antimony (meglumine antimoniate) 20 mg/kg IV or IM every 4 weeks (BII), or
Pentamidine 4 mg/kg (maximum 300 mg) IV every 2–4 weeks (BII)

ART should be initiated or optimized as soon as possible (AIII).

Pentavalent antimony is for investigational use only.

For miltefosine, visit www.profounda.com.

Cutaneous

For Initial Infection

Liposomal amphotericin B 4 mg/kg IV daily for 10 days (BIII) to achieve total dose of 20–60 mg/kg, or
Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on Days 1–5, 10, 17, 24, 31, 38) to achieve total dose of 20–60 mg/kg (BIII), or
Miltefosine 2.5 mg/kg/day PO in two or three divided doses for 28 days (maximum 150 mg per day) (BIII), or
Pentavalent antimony (meglumine antimoniate) 20 mg/kg IV or IM daily for 28 days (BIII)

Chronic Maintenance Therapy

May be indicated in immunocompromised patients with multiple relapses (CIII)
Drugs and doses same as for visceral leishmaniasis

Possible Options

Cryotherapy, or
Topical paromomycin, or
Intralesional pentavalent antimony (meglumine antimoniate) or pentamidine, or
PO or IV fluconazole (L. major and L. mexicana)
IV pentamidine
Local heat therapy
No data exist for any of these agents in patients with HIV; choice and efficacy are dependent on species of Leishmania.

ART should be initiated or optimized as soon as possible (AIII).

Pentavalent antimony is for investigational use only.

For miltefosine, visit www.profounda.com.

Malaria

Because Plasmodium falciparum malaria can progress within hours from mild symptoms or low-grade fever to severe disease or death, all HIV-infected patients with confirmed or suspected P. falciparum infection should be hospitalized for evaluation, initiation of treatment, and observation (AIII).

Treatment recommendations for HIV-infected patients are the same as for HIV-uninfected patients (AIII).

Choice of therapy is guided by the degree of parasitemia, the species of Plasmodium, the patient’s clinical status, region of infection, and the likely drug susceptibility of the infected species, and can be found at https://www.cdc.gov/malaria.

When suspicion for malaria is low, antimalarial treatment should not be initiated until the diagnosis is confirmed.

For treatment recommendations for specific regions, clinicians should refer to the following web link: http://www.cdc.gov/malaria.

or call the CDC Malaria Hotline: 770-488-7788, Monday–Friday, 8 a.m.–4:30 p.m. ET; or 7704887100 after hours.

Microsporidiosis

For GI Infections Caused by Enterocytozoon bienuesi

Initiate or optimize ART with immune restoration to CD4 count >100 cells/mm³(AII); plus
Manage dehydration and diarrhea with fluid support (AII) and malnutrition and wasting with nutritional supplements (AIII).

For Intestinal and Disseminated (Not Ocular) Infections Caused by Microsporidia Other Than E. bienuesi and Vittaforma corneae

Albendazole 400 mg PO twice daily (AII), continue until CD4 count >200 cells/mm³ for >6 months after initiation of ART (BIII)

For Disseminated Disease Caused by Trachipleistophora or Anncaliia

Itraconazole 400 mg PO daily plus albendazole 400 mg PO twice daily (CIII)

For Ocular Infection

Topical fumagillin bicylohexylammonium (Fumidil B) eye drops 3 mg/mL in saline (fumagillin 70 µg/mL): Two eye drops every 2 hours for 4 days, then two eye drops four times daily (investigational use only in United States) (BII) plus albendazole 400 mg PO twice daily, for management of systemic infection (BIII)

If CD4 Count >200 Cells/mm³

Continue until symptoms resolve (CIII).

If CD4 Count ≤200 Cells/mm³

Continue until resolution of ocular symptoms and CD4 count increases to >200 cells/mm³ for >6 months in response to ART (BIII).

For GI Infections Caused by E. bienuesi

Fumagillin 60 mg/day (BII) and TNP-470 (a synthetic analog of fumagillin) (BIII) may be effective, but neither is available in the United States.
Nitazoxanide (1,000 mg twice daily) may have some effect, but response may be minimal in patients with low CD4 cell counts (CIII).

Anti-motility agents can be used for diarrhea control if required (BIII).

Mpox

For People With Mild to Moderate Disease Who Are Not at Risk for Severe Disease

Supportive care, including adequate pain control (BIII), and referral to clinical trials, if available (CIII). CDC can provide additional guidance to clinicians with patient management questions (see Other Comments for contact information).

For Severe Disease or People at Risk for Severe Disease (See Other Comments for Definition)

Tecovirimat 600 mg PO every 12 hours (40 to <120 kg) or every 8 hours (≥120 kg) for 14 days (BIII) within 30 minutes of a fatty meal, or
Tecovirimat 200 mg IV every 12 hours for 14 days (35 to <120 kg) or 300 mg IV every 12 hours (≥120 kg) infused over 6 hours (BIII) if concern exists regarding altered GI absorption capacity, inability to take PO, or severity of illness

Adjunctive Therapy

Cidofovir 5 mg/kg/week IV for two doses with saline hydration before and after therapy and probenecid 2 g PO 3 hours before the dose followed by 1 g PO 2 hours after the dose and 1 g PO 8 hours after the dose (total of 4 g) (BIII), or
Brincidofovir 200 mg PO once weekly for two doses (BIII), or
VIGIV 6,000–9,000 units/kg IV single dose (BIII)

For Ocular Mpox

Tecovirimat 600 mg PO every 12 hours (40 to <120 kg) or every 8 hours (≥120 kg) for 14 days (BIII) within 30 minutes of a fatty meal, plus
Trifluridine (Viroptic) 1 drop into affected eye(s) every 2 hours when awake (max: 9 drops/day) until reepithelialization, then every 4 hours (min: 5 drops/day) for 7 days, or until all periocular lesions have healed (BIII) in consultation with an ophthalmologist (BIII)
- Prolonged use of trifluridine beyond 21 days might cause corneal epithelial toxicity and should be avoided (AII).

None

People with severe mpox or are at high risk for severe mpox should receive directed mpox antiviral treatment (BIII) with early consultation with CDC or an expert in mpox treatment and prompt use of combination therapy, ideally at the time of the first medical encounter and after considering the risks and benefits (CIII). Contact: [email protected] or 770-488-7100

Tecovirimat, brincidofovir, and VIGIV are available via expanded access or emergency IND.

People with severe immunocompromise might benefit from extended treatment (i.e., >14 days) if new confirmed mpox lesions occur or existing lesions or symptoms worsen despite treatment (CIII).

Effective ART should be initiated as soon as possible (AIII).

Definition for Severe Disease: Hemorrhagic disease; lesions affecting ≥25% of body surface that may be confluent, necrotic, and/or hemorrhagic in appearance or cause sepsis; disease resulting in airway compromise or affecting the nervous system; cardiac and/or neurologic disease; ocular or periorbital infections; other conditions requiring hospitalization. Consult the CDC’s Tecovirimat webpage for more details.

Definition for at Risk for Severe Disease: Not virologically suppressed, CD4 counts <200 cells/mm³, have another immunocompromising condition, have atopic dermatitis/other conditions affecting skin integrity, or are children, pregnant, or breastfeeding. Consult the CDC’s Tecovirimat webpage for more details.

Mycobacterium avium Complex (MAC) Disease

At Least Two Drugs as Initial Therapy to Prevent or Delay Emergence of Resistance (AII)

Clarithromycin 500 mg PO twice daily (AI) plus ethambutol 15 mg/kg PO daily (AI), or
Azithromycin 500–600 mg plus ethambutol 15 mg/kg PO daily (AII) if drug interaction or intolerance precludes the use of clarithromycin.

Duration

At least 12 months (AII)
Shorter duration may be considered. CD4 count should be >100 cells/mm³ for ≥6 months in response to ART before discontinuation of MAC therapy (CIII).

Some experts would add a third drug if more severe disease is present.

Rifabutin 300 mg PO daily (dose adjustment may be necessary based on drug interactions) (CI)
- Refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table of the Mycobacterium tuberculosis section for dosing recommendations.

Some experts would add a fourth drug if the risk of mortality is high, emergence of drug resistance is likely, CD4 count <50 cells/mm³, high mycobacterial loads (>2 log₁₀ CFU/mL of blood) are present, or effective ART is absent (CIII).

A fluoroquinolone (CIII) (e.g., moxifloxacin 400 mg PO daily or levofloxacin 500 mg PO daily), or
An injectable aminoglycoside (CIII) (e.g., amikacin 10–‍15 mg/kg IV daily or streptomycin 1 g IV or IM daily).

Testing of susceptibility to clarithromycin and azithromycin is recommended.

NSAIDs can be used for moderate to severe symptoms attributed to IRIS (BIII).

If IRIS symptoms persist, a short course (i.e., 4–‍8 weeks) of a systemic corticosteroid (equivalent to 20–40 mg of prednisone daily) can be used (BII).

Bedaquiline, tedizolid, linezolid, and omadacycline have demonstrated in vitro activity against clinical isolates of MAC; these might also be considered in people with refractory MAC disease.

Mycobacterium tuberculosis (TB) Disease: Drug-Susceptible TB

Refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis section for dosing recommendations.

Intensive Phase (8 Weeks)

INH (plus pyridoxine) plus (RIF or RFB) plus PZA plus EMB PO daily (AI)
If drug susceptibility report shows sensitivity to INH and RIF, then EMB may be discontinued before the end of 2 months (AI).

Continuation Phase (Duration Depends on Site and Severity of Infection as noted below)

INH (plus pyridoxine) plus (RIF or RFB) PO daily (AII)

Total Duration of Therapy for Drug-Susceptible TB

Pulmonary, Uncomplicated TB: 6 months (BII)
Pulmonary TB with Positive Culture at 8 Weeks of TB Treatment, or Severe Cavitary or Disseminated Extrapulmonary TB: 9 months (BII)
TB Meningitis: 9–12 months (BII)
Extrapulmonary TB in Other Sites: 6 months (BII)

Only for Patients Receiving an Efavirenz-Based ARV Regimen; Not Recommended for Extrapulmonary TB

Intensive Phase (8 Weeks)

INH plus RPT 1,200 mg plus moxifloxacin 400 mg plus PZA plus pyridoxine 25–50mg PO daily (AI)^c

Continuation Phase (9 Weeks)

INH plus RPT 1200 mg plus moxifloxacin 400 mg plus pyridoxine 25–50mg PO daily (AI)

DOT is recommended for all patients (AII).

All rifamycins may have significant pharmacokinetic interactions with ARV drugs; please refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis section and the Drug–Drug Interactions section of the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations.

Therapeutic drug monitoring should be considered in patients receiving rifamycin and interacting ART.

Adjunctive corticosteroids for TB meningitis (AII): Dexamethasone 0.3–‍0.4mg/kg/day for 2–‍4 weeks, then taper by 0.1 mg/kg per week until 0.1 mg/kg, then 4 mg per day, and taper by 1 mg/week for total of 12 weeks.

At doses above 16 mg, dexamethasone is a CYP3A4 inducer and can decrease certain ARVs that are substrates of CYP3A4 (e.g., DOR, RPV, and protease inhibitors). Consultation with a pharmacist is recommended.

Adjunctive corticosteroid is not recommended for patients with TB pericarditis (AI).

See text for recommendations on preventing and managing paradoxical TB-IRIS, including prednisone dosing recommendations.

Mycobacterium tuberculosis (TB) Disease: Drug-Resistant TB

Refer to the Dosing Recommendations for Use of ARV and Anti-TB Drugs for Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis section for dosing recommendations.

Empiric Therapy for Suspected Resistance to Rifamycin^d +/- Resistance to Other Drugs

INH (plus pyridoxine) plus PZA plus EMB plus (moxifloxacin or levofloxacin) plus (linezolid or amikacin^e) (BII)

Confirmed Resistance to INH

(Moxifloxacin or levofloxacin) plus (RIF or RFB) plus EMB plus PZA for 6 months (BII)

Confirmed Resistance to Rifamycin +/- Other Drugs (AI)

For 14 Days

Pretomanid 200 mg plus linezolid 600 mg plus moxifloxacin 400 mg daily plus bedaquiline 400 PO daily, followed by

For 24 Weeks

Pretomanid 200 mg plus linezolid 600 mg plus moxifloxacin 400 mg daily, and
Bedaquiline 200 mg PO three times per week

Omit moxifloxacin if resistant to fluoroquinolones (AI).

Duration

6–24 months (see Managing Drug-Resistant TB in the Mycobacterium tuberculosis section for discussion)

Confirmed Resistance to Rifamycin +/- Other Drugs

Therapy should be individualized based on drug susceptibility results and clinical and microbiologic responses, to include ≥5 active drugs, and with close consultation with experienced specialists (BIII).

Pneumocystis Pneumonia (PCP)

People with HIV who develop PCP despite TMP-SMX prophylaxis can usually be treated with standard doses of TMP-SMX (BIII).

Duration of PCP treatment: 21 days (AII)

For Moderate to Severe PCP

TMP-SMX: (TMP 15–‍20 mg/kg/day and SMX 75–‍100 mg/kg/day) IV given in divided doses every 6 or 8 hours (AI); may switch to PO formulations after clinical improvement (AI).

For Mild to Moderate PCP

TMP-SMX: (TMP 15–‍20 mg/kg/day and SMX 75–‍100 mg/kg/day) PO given in three divided doses (AI), or
TMP-SMX: (160 mg/800 mg or DS) two tablets PO three times daily (AI)

Secondary Prophylaxis, After Completion of PCP Treatment

TMP-SMX DS: one tablet PO daily (AI), or
TMP-SMX (80 mg/400 mg or SS): one tablet PO daily (AI)

For Moderate to Severe PCP

Primaquine 30 mg (base) PO daily plus (clindamycin 600 mg IV every 6 hours or 900 mg IV every 8 hours) or (clindamycin 450 mg PO every 6 hours or 600 mg PO every 8 hours) (AI) (some clinicians prefer this option because it is more effective and less toxic than pentamidine), or
Pentamidine 4 mg/kg IV daily infused over ≥60 minutes (AI); can reduce dose to 3 mg/kg IV daily in the event of toxicities (BI)

For Mild to Moderate PCP

Dapsone 100 mg PO daily plus TMP 15 mg/kg/day PO given in three divided doses (BI), or
Primaquine 30 mg (base) PO daily plus (clindamycin 450 mg PO every 6 hours or 600 mg PO every 8 hours) (BI), or
Atovaquone 750 mg PO twice daily with food (BI)

Secondary Prophylaxis, After Completion of PCP Treatment

The following regimens can be used for people who are seropositive or seronegative for Toxoplasma gondii:

TMP-SMX DS: one tablet PO three times weekly (BI), or
Dapsone 50 mg PO daily with pyrimethamine^b 50 mg plus leucovorin 25 mg PO weekly (BI), or
Dapsone 200 mg plus pyrimethamine^b 75 mg plus leucovorin 25 mg PO weekly (BI), or
Atovaquone 1,500 mg PO daily with food (BI)

The following regimens should only be used if the person is seronegative for Toxoplasma gondii:

Dapsone 100 mg PO daily (BI), or
Aerosolized pentamidine 300 mg monthly via Respirgard II nebulizer (BI), or
Intravenous pentamidine 300 mg every 28 days (CIII)

Indications for Adjunctive Corticosteroids for Moderate to Severe PCP (AI)

PaO₂<70 mmHg at room air, or
A-a gradient ≥35 mmHg

Prednisone Doses (Beginning as Early as Possible and Within 72 Hours of PCP Therapy) (AI)

Days 1–5: 40 mg PO twice daily
Days 6–10: 40 mg PO daily
Days 11–21: 20 mg PO daily

IV methylprednisolone can be administered as 80% of prednisone dose.

Benefit of using a corticosteroid if started after 72 hours of treatment is unknown, but some clinicians will use it for moderate to severe PCP (BIII).

Whenever possible, patients should be tested for G6PD before use of dapsone or primaquine. Alternative therapy should be used in patients found to have G6PD deficiency.

Patients who are receiving pyrimethamine^b/sulfadiazine for the treatment or suppression of toxoplasmosis do not require additional PCP prophylaxis (AII).

If TMP-SMX is discontinued because of a mild adverse reaction, re‍institution should be considered after the reaction resolves (AII). The dose can be increased gradually (desensitization) (BI) or the drug can be given at a reduced dose or frequency (CIII).

TMP-SMX should be permanently discontinued in patients with possible or definite Stevens-Johnson syndrome or toxic epidermal necrosis (AIII). See alternative options.

Progressive Multifocal Leukoencephalopathy (PML)/JC Virus Infections

There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV.

Initiate ART immediately in ART-naive patients (AII).

Optimize ART to achieve viral suppression in patients who develop PML and receive ART but remain viremic (AIII).

None

Corticosteroids may be used for PML-IRIS (BIII). The optimal corticosteroid regimen has not been established but should be tailored to individual patients.

ART should not be discontinued during PML-IRIS (AIII).

Syphilis (Treponema pallidum Infection)

Early-Stage (Primary, Secondary, and Early-Latent Syphilis)

Benzathine penicillin G 2.4 million units IM for one dose (AII)

Late-Latent Disease (>1 Year) or of Unknown Duration

Benzathine penicillin G 2.4 million units IM weekly for three doses (AII)

Late-Stage (Tertiary–Cardiovascular or Gummatous Disease)

Benzathine penicillin G 2.4 million units IM weekly for three doses (AII)

Note: Rule out neurosyphilis before initiation of benzathine penicillin. Persons with CSF abnormalities should be treated with a regimen for neurosyphilis [AII].)

Neurosyphilis, Otic, or Ocular Syphilis

Aqueous crystalline penicillin G 18–24 million units per day (administered as 3–4 million units IV every 4 hours or by continuous IV infusion) for 10–14 days (AII) +/- benzathine penicillin G 2.4 million units IM x 1 dose after completion of IV therapy (CIII)

Early-Stage (Primary, Secondary, and Early-Latent Syphilis)

For Penicillin-Allergic Patients

Doxycycline 100 mg PO twice daily for 14 days (BII), or
Ceftriaxone 1 g IM or IV daily for 10–14 days (BII)

Late-Latent Disease (>1 Year) or of Unknown Duration

For Penicillin-Allergic patients

Doxycycline 100 mg PO twice a day for 28 days (BIII)

Neurosyphilis

Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg PO four times a day for 10–‍14 days (BII) or
For penicillin-allergic patients, desensitization to penicillin is the preferred approach (BIII); if not feasible and the patient is not pregnant, ceftriaxone 2 g IV daily for 10–‍14 days (BII).

The efficacy of non-penicillin alternatives has not been evaluated in patients with HIV, and they should be used only with close clinical and serologic monitoring.

People with penicillin allergy whose compliance or follow-up cannot be ensured should be desensitized and treated with benzathine penicillin (AII).

For management of early syphilis during pregnancy, limited evidence indicates a second dose of benzathine penicillin G 2.4 million units IM one week after the single dose treatment may be of benefit for congenital syphilis prevention (BII).

The Jarisch-Herxheimer reaction is an acute febrile reaction accompanied by headache and myalgia that can occur within the first 24 hours after therapy for syphilis. This reaction occurs most frequently in patients with early syphilis, high non-treponemal titers, and prior penicillin treatment.

Procaine penicillin has been discontinued by the manufacturer as of June 13, 2023 (see FDA Drug Shortages).

Talaromycosis (Penicilliosis)

Induction Therapy

Liposomal amphotericin B 3–‍5 mg/kg/day IV (AIII)

Duration

2 weeks (AIII), followed by consolidation therapy

Consolidation Therapy

Itraconazole 200 mg PO every 12 hours for 10 weeks (AI), followed by chronic maintenance therapy

Chronic Maintenance Therapy

Itraconazole 200 mg PO once daily (AI)

Induction Therapy

Amphotericin B deoxycholate 0.7 mg/kg/day IV (if liposomal amphotericin B is not available) (AI)

Duration

2 weeks (AI), followed by consolidation therapy

If Amphotericin B Is Not Available, Contraindicated, or Not Tolerated

Voriconazole 6 mg/kg IV every 12 hours on Day 1 (loading dose), then 4 mg/kg IV every 12 hours (BII), or
Voriconazole 600 mg PO every 12 hours on Day 1 (loading dose), then 400 mg PO every 12 hours (BII)
Duration: 2 weeks (BII), followed by consolidation therapy with itraconazole (preferred) or voriconazole

Consolidation Therapy

Voriconazole 200 mg PO every 12 hours for 10 weeks (BII), followed by chronic maintenance therapy

Chronic Maintenance Therapy

Itraconazole should be used (AI). Optimal dose of voriconazole for maintenance therapy has not been studied.

Itraconazole is not recommended as induction therapy for talaromycosis (AI).

ART should be initiated as early as 1 week after initiation of treatment for talaromycosis (AII).

Itraconazole and voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bidirectional. Refer to Drug–Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines for dosage recommendations.

Itraconazole and voriconazole concentrations should be monitored beginning at 5 days and dose adjusted as needed to obtain serum trough concentrations for itraconazole should be >0.5 µg/mL (for a combined itraconazole plus hydroxyitraconazole level) and >1 µg/mL for voriconazole (BIII).

Itraconazole solution is generally preferred over the capsule formulation because of improved bioavailability.

Toxoplasma gondii Encephalitis

Treatment of Acute Infection

Pyrimethamine^b 200 mg PO one time, followed by weight-based therapy (AI):
- If ≤60 kg: Pyrimethamine^b 50 mg PO once daily plus sulfadiazine 1,000 mg PO every 6 hours plus leucovorin 10–25 mg PO once daily
- If >60 kg: Pyrimethamine^b 75 mg PO once daily plus sulfadiazine 1,500 mg PO every 6 hours plus leucovorin 10–‍25 mg PO once daily

Note: Leucovorin dose can be increased to 50 mg daily or twice a day.

TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg) IV or PO twice a day (AII)

Duration for Acute Therapy

At least 6 weeks (BII); longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks
After completion of acute therapy, all patients should be initiated on chronic maintenance therapy.

Chronic Maintenance Therapy

Pyrimethamine^b 25–50 mg PO daily plus sulfadiazine 2,000–‍‍4,000 mg PO daily (in 2–‍4 divided doses) plus leucovorin 10–25 mg PO daily (AI), or
TMP-SMX DS one tablet twice a day (AII)

Treatment of Acute Infection

Pyrimethamine^b (leucovorin)* plus clindamycin 600 mg IV or PO every 6 hours (AI), or
Atovaquone 1,500 mg PO twice a day with food plus pyrimethamine^b(leucovorin)* (BII), or
Atovaquone 1,500 mg PO twice a day with food plus sulfadiazine 1,000–1,500 mg PO every 6 hours (weight-based dosing, as in preferred therapy) (BII), or
Atovaquone 1,500 mg PO twice a day with food (BII)

Chronic Maintenance Therapy

(Pyrimethamine^b 25–‍50 mg plus leucovorin 10–‍25 mg) PO daily plus clindamycin 600 mg PO every 8 hours plus (BI), or
Atovaquone 750–‍1,500 mg PO twice a day plus (pyrimethamine^b 25 mg plus leucovorin 10 mg) PO daily (BII), or
Atovaquone 750–‍1,500 mg PO twice a day plus sulfadiazine 2,000–‍4,000 mg PO daily (in two to four divided doses) (BII), or
Atovaquone 750–‍1,500 mg PO twice a day with food (BII)

* Pyrimethamine^b and leucovorin doses are the same as for preferred therapy.

If pyrimethamine is unavailable or there is a delay in obtaining it, TMP-SMX should be used in place of pyrimethamine-sulfadiazine (AII).

For patients with a history of sulfa allergy, sulfa desensitization should be attempted using one of several published strategies (BI).

Atovaquone should be administered until therapeutic doses of TMP-SMX are achieved (CIII).

Adjunctive corticosteroids (e.g., dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema (BIII); discontinue as soon as clinically feasible.

Antiseizure medications should be administered to patients with a history of seizures (AII) and continued through acute treatment (BII) but should not be used as seizure prophylaxis (BII).

If clindamycin is used in place of sulfadiazine, additional therapy must be added to prevent PCP (AII).

Varicella Zoster Virus (VZV) Disease

Primary Varicella Infection (Chickenpox)

Uncomplicated Cases

Initiate as soon as possible after lesion onset and continue for 5–‍7 days:
- Valacyclovir 1 g PO three times a day (AII), or
- Famciclovir 500 mg PO three times a day (AII)

Severe or Complicated Cases

Acyclovir 10 mg/kg IV every 8 hours for 7–‍10 days (AIII)
May switch to oral valacyclovir, famciclovir, or acyclovir after defervescence and clinical improvement if no evidence of visceral involvement (BIII).

Herpes Zoster (Shingles)

Initiate therapy as soon as possible and within 1 week of rash onset, or any time prior to full crusting of lesions (AIII).

Acute, Localized, Dermatomal

For 7–10 days. Consider longer duration if lesions are slow to resolve (CIII).
Valacyclovir 1 g PO three times a day (AII), or
Famciclovir 500 PO mg three times a day (AII)

Extensive Cutaneous Lesion or Visceral Involvement

Acyclovir 10 mg/kg IV every 8 hours until clinical improvement is evident (AII)
May switch to PO therapy (valacyclovir, famciclovir, or acyclovir) after clinical improvement (i.e., when no new vesicle formation and improvement of signs and symptoms of visceral VZV) to complete a total 10- to 14-day course (BIII).

Herpes Zoster Ophthalmicus

Late Dendriform Lesions of the Corneal Epithelium

Oral antiviral treatment as stated above for “Acute, Localized, Dermatomal” herpes zoster, followed by suppressive therapy.
If/when patient is not receiving oral antivirals, topical antivirals should be administered until resolution of lesions (AIII).
- Trifluridine 1% eye drops: see mpox for dosing (BIII)
- Ganciclovir 0.15% gel: see HSV for dosing (BIII)

Stromal Keratitis and Anterior Uveitis

Oral antiviral treatment as stated above for “Acute, Localized, Dermatomal” herpes zoster, followed by suppressive therapy.
Alongside initial systemic antiviral treatment, topical corticosteroids should be administered (AII). Typical regimen using prednisolone acetate 1% drops: 1 drop in affected eye every 2 hours while awake (maximum eight times daily) until clinical response, then slow taper over many weeks if clinical improvement continues, eventually decreasing to 1–2 drops daily for at least 1 year (AII).

Suppressive Therapy

Valacyclovir 1 g PO daily for 12 months to prevent development of new, or exacerbations of existing, keratitis lesions and uveitis (AII).

ARN

Initial Therapy

Acyclovir 10 mg/kg IV every 8 hours for 10–14 days or until lesion healing (AIII), followed by suppressive therapy.
A single adjunctive intravitreal injection of ganciclovir (2 mg/0.05 mL) can also be given as a part of induction treatment (BIII). Additional injections can be given if there is a concern for lack of treatment response, but injections should not be given more frequently than twice weekly (BIII).

Suppressive Therapy

Valacyclovir 1 g PO daily (AIII) for ≥6 months

PORN

Optimal antiviral therapy and duration of therapy remains undefined and should be managed by an ophthalmologist experienced in the management of VZV ocular disease (AIII).
Acyclovir 10 mg/kg IV every 8 hours or ganciclovir 5 mg/kg IV every 12 hours (AIII), plus
Intravitreal ganciclovir 2 mg/0.05 mL or intravitreal foscarnet 1.2 mg/0.05 mL weekly (BIII)

Primary Varicella Infection (Chickenpox)

Uncomplicated Cases

Initiate as soon as possible after lesion onset and continue for 5–7 days:
- Acyclovir 800 mg PO five times a day (BII)

Herpes Zoster (Shingles)

Initiate therapy as soon as possible and within 1 week of rash onset, or any time prior to full crusting of lesions (AIII).

Acute, Localized, Dermatomal

For 7–10 days. Consider longer duration if lesions are slow to resolve (CIII).
Acyclovir 800 mg PO five times a day (BII)

ARN

Suppressive Therapy

Following initial therapy, acyclovir 800 mg PO twice daily (CIII) for ≥6 months

Consultation with an ophthalmologist experienced in the management of patients with VZV ocular disease is strongly recommended (AIII).

People with V1 herpes zoster should have an ophthalmologic exam; patients with normal eye examinations initially should receive follow-up eye examinations, even after the skin lesions heal (AIII).

All people with HIV should receive ART as soon as possible after diagnosis of HIV infection (AIII). The presence of disease caused by VZV is not an indication to defer or discontinue ART.

^a TAF 10-mg dose is in the FDC tablets of EVG/c/TAF/FTC and DRV/c/TAF/FTC; when TAF is used with other antiretrovirals, the dose is 25 mg.

^b Refer to Daraprim Direct for information on accessing pyrimethamine.

^cThis regimen was not studied and is not recommended for people who are pregnant, breastfeeding, <40 kg, or who have most types of extrapulmonary TB (other than pleural TB or lymphadenitis).

^dMany patients with RIF resistance also have resistance to isoniazid. Susceptibility should be confirmed in any patient with RIF resistance to determine if isoniazid can be included in the treatment regimen.

^eGiven the risk of ototoxicity and nephrotoxicity with aminoglycosides, use of amikacin should generally be restricted to bridging regimens, while awaiting availability of less toxic medications and/or results of drug-susceptibility testing.

For information regarding the evidence ratings, refer to the Rating System for Prevention and Treatment Recommendations in the Introduction section of the Adult and Adolescent Opportunistic Infection Guidelines.

Key: +/- = with or without; 3TC = lamivudine; A-a = alveolar-arterial; AASLD = American Association for the Study of Liver Diseases; ACTG = AIDS Clinical Trials Group; ARN = acute retinal necrosis; ART = antiretroviral therapy; ARV = antiretroviral; CD4 = CD4 T lymphocyte; CDC = Centers for Disease Control and Prevention; CDI = Clostridium difficile infection; CFU = colony-forming unit; CNS = central nervous system; CrCl = creatinine clearance; CSF = cerebrospinal fluid; DAA = direct-acting antiviral; DOT = directly observed therapy; DLBCL = diffuse large B-cell lymphoma; DRV = darunavir; DS = double strength; EMB = ethambutol; EPOCH = etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin combination therapy; EVG = elvitegravir; FDA = U.S. Food and Drug Administration; FDC = fixed-dose combination; FMT = fecal microbiota therapy; FTC = emtricitabine; G6PD = glucose-6-phosphate dehydrogenase; GI = gastrointestinal; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HD = hemodialysis; HHV-‍8 = human herpesvirus 8; HSV = herpes simplex virus; IDSA = Infectious Diseases Society of America; IM = intramuscular; IND = investigational new drug; INH = isoniazid; IRIS = immune reconstitution inflammatory syndrome; IRU = immune recovery uveitis; IV = intravenous; KS = Kaposi sarcoma; KSHV = Kaposi sarcoma–associated herpesvirus; LFA = lateral flow assay; LP = lumbar puncture; MCD = multicentric Castleman’s disease; MIC = minimum inhibitory concentration; MSM = men who have sex with men; NSAID = nonsteroidal anti-‍inflammatory drugs; OI = opportunistic infection; PaO₂ = partial pressure of oxygen; PCP = Pneumocystis pneumonia; PEL = primary effusion lymphoma; PO = oral; PORN = progressive outer retinal necrosis; PZA = pyrazinamide; RFB = rifabutin; RIF = rifampin; RPT = rifapentine; SMX = sulfamethoxazole; SS = single strength; SVR = sustained virologic response; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate; TMP = trimethoprim; VIGIV = vaccinia immune globulin intravenous; VZV = varicella zoster virus; WHO = World Health Organization

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Table 2. Treatment of HIV-Associated Opportunistic Infections (Includes Recommendations for Acute Treatment and Secondary Prophylaxis/Chronic Suppressive/Maintenance Therapy)