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

For People With HIV and CD4 >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 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 <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.

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

For Severe or Nonsevere CDI

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

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).

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)

• 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. has 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)

Anti-motility 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.

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).

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.)

For Acute or Reactivated Disease

• Benznidazole 5–8 mg/kg/day PO in two divided doses for 60 days (BIII) (commercially available at http://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)

Treatment is effective in reducing parasitemia and preventing clinical symptoms or slowing disease progression. These drugs have limited efficacy, however, 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).

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.

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 Non-Severe 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 Non-Severe 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).

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.

• 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 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).

CMV Retinitis Induction Therapy (followed by Chronic Maintenance Therapy)

For Immediate Sight-Threatening Lesions (within 1,500 microns of the fovea)

• Ganciclovir 5 mg/kg every 12 hours IV or valganciclovir 900 mg PO twice a day or for 14–‍21 days (AI) (some prefer IV ganciclovir initially and transition to PO valganciclovir when there is evidence of clinical response) with or without
• Intravitreal injections of ganciclovir (2 mg) or foscarnet (2.4 mg) to rapidly achieve high intraocular concentration, continue weekly until lesion inactivity is achieved (AIII); plus

For Peripheral Lesions

• Valganciclovir 900 mg PO twice a day for 14–21 days, then 900 mg once daily (AI)

Maintenance Therapy

• Valganciclovir 900 mg PO daily (AI) for 3–6 months until ART-induced immune recovery

CMV Esophagitis or Colitis

• Ganciclovir 5 mg/kg IV every 12 hours; may switch to valganciclovir 900 mg PO every 12 hours once the patient can tolerate oral therapy (BI)
• Valganciclovir 900 mg PO every 12 hours may be considered as initial therapy in mild diseases (CIII)
• Duration: 21–42 days or until symptoms have resolved (CII)
• Maintenance therapy is usually not necessary, but should be considered after relapses (BII).

Well-Documented, Histologically Confirmed CMV Pneumonia

• Experience for treating CMV pneumonitis in HIV patients is limited. Use of IV ganciclovir or IV foscarnet is reasonable (doses same as for CMV retinitis) (CIII).
• The optimal duration of therapy and the role of oral valganciclovir have not been established.

CMV Neurological Disease

Note: Treatment should be initiated promptly.

• Ganciclovir 5 mg/kg IV every 12 hours plus (foscarnet 90 mg/kg IV every 12 hours or 60 mg/kg IV every 8 hours) to stabilize disease and maximize response, continue until symptomatic improvement and resolution of neurologic symptoms (CIII)
• The optimal duration of therapy and the role of oral valganciclovir have not been established.

CMV Retinitis

For Immediate Sight-Threatening Lesions (within 1,500 microns of the fovea): Intravitreal therapy as listed in the Preferred section, plus one of the following:

Alternative Systemic Induction Therapy (followed by Chronic Maintenance Therapy)

• Foscarnet 90 mg/kg IV every 12 hours or 60 mg/kg every 8 hours for 14–21 days (BI), or
• Cidofovir 5 mg/kg/week IV for 2 weeks; saline hydration before and after therapy and probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g) (CI) (Note: This regimen should be avoided in patients with sulfa allergy because of cross hypersensitivity with probenecid.)

Chronic Maintenance (for 3–‍6 months until ART-induced immune recovery)

• Foscarnet 90–120 mg/kg IV once daily (AI), or
• Cidofovir 5 mg/kg IV every other week with saline hydration and probenecid as above (BI)

CMV Esophagitis or Colitis

• Foscarnet 90 mg/kg IV every 12 hours or 60 mg/kg every 8 hours (BI) for patients with treatment-limiting toxicities to ganciclovir or with ganciclovir resistance, or
• Valganciclovir 900 mg PO every 12 hours in milder disease and if able to tolerate PO therapy (BII), or
• Duration: 21–42 days or until symptoms have resolved (CII)
• For mild disease, if ART can be initiated without delay, consider withholding CMV therapy (CIII).

The choice of therapy for CMV retinitis should be individualized, based on tolerance of systemic medications, prior exposure to anti-CMV drugs, and location of the lesion (AIII).

Initial therapy in patients with CMV retinitis, esophagitis, colitis, and pneumonitis should include initiation or optimization of ART (BIII).

Given the evident benefits of systemic therapy in preventing contralateral eye involvement, reduce CMV visceral disease and improve survival. Whenever feasible, treatment should include systemic therapy.

The ganciclovir ocular implant, which is effective for treatment of CMV retinitis, is no longer available.

Routine (i.e., every 3 months) ophthalmologic follow-up is recommended after stopping chronic maintenance therapy for early detection of relapse or IRU, and then periodically after sustained immune reconstitution (AIII).

IRU may develop in the setting of immune reconstitution.

Treatment of IRU

Periocular, intravitreal, or short courses of systemic steroid (BIII)

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

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

If CrCl ≥60 mL/min:

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

Note: TAF 10 mg is in the STR tablets of EVG/COBI/TAF/FTC and DRV/COBI/TAF/FTC; when TAF is used with other ARVs, the dose is 25 mg.

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 or TAF), with a fully suppressive ART regimen, or
• ART with renally dose-adjusted TDF and FTC or 3TC can be used (BIII) if recovery of renal function is unlikely.

If on HD:

• (TDF or TAF) plus (FTC or 3TC) can be used. Refer to Table 6 for dosing recommendations. TAF and FTC do not require renal dose adjustment in people receiving HD.

Duration

• Continue treatment indefinitely (BIII).

For People Not on ART

• Anti-HBV therapy is indicated for those who meet criteria for treatment according to the AASLD Hepatitis B Guidance.
• Peginterferon alfa-2a 180 mcg SQ once weekly for 48 weeks (CIII), or
• Peginterferon alfa-2b 1.5 mcg/kg SQ once weekly for 48 weeks (CIII)

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

Chronic administration of 3TC or FTC as the only active drug against HBV 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 telbivudine and FTC, and partial resistance to entecavir. These agents should not be used among people found to have 3TC-resistant HBV (AI). If 3TC resistance is suspected or documented, TDF or TAF should be added to the ART regimen (BIII).

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

If anti-HBV therapy is discontinued and a flare occurs, therapy should be re-instituted 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 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 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.

Orolabial Lesions (for 5–10 Days)

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

Initial or Recurrent Genital HSV (for 5–14 days)

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

Severe Mucocutaneous HSV

• Initial therapy acyclovir 5 mg/kg IV every 8 hours (AIII)
• After lesions begin to regress, change to PO therapy as above. Continue until lesions are completely healed.

Chronic Suppressive Therapy

For Patients with Severe Recurrences of Genital Herpes (AI) or Patients Who Want to Minimize Frequency of Recurrences (AI)

• Valacyclovir 500 mg PO twice a day (AI), or
• Famciclovir 500 mg PO twice a day (AI), or
• Acyclovir 400 mg PO twice a day (AI)
• Continue indefinitely, regardless of CD4 count.

For Acyclovir-Resistant HSV

Preferred Therapy

• Foscarnet 80–120 mg/kg/day IV in two to three divided doses until clinical response (AI)

Alternative Therapy (CIII)

• IV cidofovir (dosage as in CMV retinitis), or
• Topical trifluridine 1% three times a day, or
• Topical cidofovir 1% once daily, or
• Topical imiquimod 5% three times weekly, or
• Topical foscarnet 1% five times daily

Duration of Therapy

• 21–28 days or longer

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

Extemporaneous compounding of topical products can be prepared using trifluridine ophthalmic solution and the IV formulation of cidofovir and foscarnet.

An expanded access program of oral pritelivir is now available for immunocompromised patients with acyclovir-resistant HSV infection. For more information, see the AiCuris Pritelivir website.

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 Persons With CD4 <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.

Mild to Moderate KS (Localized Involvement of Skin and/or Lymph Nodes)

• Initiate or optimize ART (AII)

Advanced KS (Visceral [AI] or Disseminated Cutaneous KS [BIII)]

• Chemotherapy (per oncology consult) plus ART
• Liposomal doxorubicin first-line chemotherapy (AI)

Primary Effusion Lymphoma

• Chemotherapy (per oncology consult) plus ART (AIII)
• PO valganciclovir or IV ganciclovir can be used as adjunctive therapy (CIII)

MCD Therapy Options (in Consultation with Specialist, Depending on HIV/HHV-8 Status, Presence of Organ Failure, and Refractory Nature of Disease)

ART (AIII) along with one of the following:

• Valganciclovir 900 mg PO twice a day for 3 weeks (CII), or
• Ganciclovir 5 mg/kg IV every 12 hours for 3 weeks (CII), or
• Valganciclovir PO or Ganciclovir IV plus zidovudine 600 mg PO every 6 hours for 7–21 days (CII)
• Rituximab +/- Prednisone (CII)
• Monoclonal antibody targeting IL-6 or IL-6 receptor (BII)

Concurrent KS and MCD

Rituximab plus liposomal doxorubicin (BII)

MCD

• Rituximab (375 mg/m² given weekly for 4–8 weeks) may be an alternative to or used adjunctively with antiviral therapy (CII).

Corticosteroids should be avoided in patients with KS, including those with KS-IRIS (AIII).

Corticosteroids are potentially effective as adjunctive therapy for MCD, but should be used with caution, especially in patients with concurrent KS.

Patients who received rituximab for MCD may experience subsequent exacerbation or emergence of KS.

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 3 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 4 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% to 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

For Acute Infection

• TMP-SMX (160 mg/800 mg) PO (or IV) four times a day for 10 days (AII), or
• TMP-SMX (160 mg/800 mg) PO (or IV) twice a day for 7–10 days (BI)
• Can start with twice a day dosing first and increase daily dose and/or duration (up to 3–‍4 weeks) if symptoms worsen or persist (BIII)
• IV therapy may be used for patients with potential or documented malabsorption.

Chronic Maintenance Therapy (Secondary Prophylaxis)

• In patients with CD4 count <200 cells/mm³, TMP-SMX (160 mg/800 mg) PO three times weekly (AI)

For Acute Infection

• Pyrimethamine^b 50–75 mg PO daily plus leucovorin 10–‍25 mg PO daily (BIII), or
• Ciprofloxacin 500 mg PO twice a day for 7 days (CI) as a second-line alternative

Chronic Maintenance Therapy (Secondary Prophylaxis)

• TMP-SMX (160 mg/800 mg) PO daily or (320 mg/1,600 mg) three times weekly (BIII)
• Pyrimethamine^b 25 mg PO daily plus leucovorin 5–‍10 mg PO daily (BIII)
• Ciprofloxacin 500 mg three times weekly (CI) as a second-line alternative

Fluid and electrolyte management in patients with dehydration (AIII).

Nutritional supplementation for malnourished patients (AIII).

Immune reconstitution with ART may result in fewer relapses (AIII).

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 2–3 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.

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 2–‍3 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 (major & 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.

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.

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.

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) eyedrops 3 mg/mL in saline (fumagillin 70 µg/mL): two eyedrops every 2 hours for 4 days, then two eyedrops 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).

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

• Tecovirimat 600 mg PO every 12 hours (<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 (<120 kg) or 300 mg IV every 12 hours (≥120 kg) if concern exists regarding altered GI absorption capacity, inability to take PO, or extent of organ systems affected by mpox (BIII)

Adjunctive Therapy for Severe Disease or at Risk for Severe Disease

• 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)

Preferred Therapy for Ocular Mpox

• Tecovirimat 600 mg PO every 12 hours (<120 kg) or every 8 hours (≥120 kg) for 14 days (CIII) within 30 minutes of a fatty meal, and
• 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 (CIII)
  • Prolonged use of trifluridine beyond 21 days might cause corneal epithelial toxicity and should be avoided (AII).

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

For severe disease, consider early intervention with adding one of the adjunctive therapies at the time of first medical encounter, in consultation with CDC or an expert in mpox treatment (CIII).

Patients with severe immunocompromise might benefit from extended treatment (i.e., >14 days) of preferred and/or adjunctive therapies if new confirmed mpox lesions occur or existing lesions worsen despite treatment.

Vaccination with any live virus vaccines should be delayed until 3 months after VIGIV administration (CIII). People who received VIGIV shortly after a live virus vaccination should be revaccinated 3 months after administration of the immune globulin (CIII).

Definition for Severe Disease or at Risk for Severe Disease: People with HIV who are not virologically suppressed or who have CD4 counts <350 cells/mm³ are considered at high risk for severe mpox. Severe mpox might manifest as hemorrhagic disease; large number of lesions, such that they are confluent; sepsis; encephalitis; ocular or periorbital infections; or other conditions requiring hospitalization.

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.

Refer to the Dosing Recommendations Treatment of Active Drug Sensitive TB table in the Mycobacterium tuberculosis Infection and Disease 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 1200 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 Anti-TB Drugs table in the Mycobacterium tuberculosis Infection and Disease 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.

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).

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.

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).

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).

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.

Persons 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).

Induction Therapy

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

Duration

• 2 weeks (AI), followed by consolidation therapy

Consolidation Therapy

• Itraconazole 200 mg PO twice daily for 10 weeks (AI), followed by chronic maintenance therapy

Chronic Maintenance Therapy

• Itraconazole 200 mg PO once daily, until CD4 count >100 cells/mm³ for ≥6 months (AII)

Induction Therapy

• Amphotericin B deoxycholate 0.7 mg/kg/day IV for 2 weeks (if liposomal amphotericin B is not available) (AI)

If Amphotericin B Is Not Available

• Voriconazole 6 mg/kg IV every 12 hours for 1 day (loading dose), then 4 mg/kg IV every 12 hours (BII), or
• Voriconazole 600 mg PO twice daily for 1 day (loading dose), then 400 mg PO twice daily (BII)

Duration

• 2 weeks (BII) followed by consolidation therapy with itraconazole (preferred) or voriconazole

Consolidation Therapy

• Voriconazole 200 mg PO twice daily for 10 weeks (BII), followed by chronic maintenance therapy

Chronic Maintenance Therapy

• Itraconazole should be used (AII). Chronic maintenance therapy with voriconazole has not been studied.

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

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

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.

TDM and dosage adjustment may be necessary to ensure triazole antifungal and ARV efficacy and reduce concentration-related toxicities. The goals of itraconazole and voriconazole trough concentrations are >0.5 mcg/mL and >1.0 mcg/mL, respectively.

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).

Primary Varicella Infection (Chickenpox)

Uncomplicated Cases

• Initiate as soon as possible after symptom 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 if no evidence of visceral involvement (BIII).

Herpes Zoster (Shingles)

Acute Localized Dermatomal

• For 7–10 days; consider longer duration if lesions are slow to resolve
• Valacyclovir 1 g PO three times a day (AII), or
• Famciclovir 500 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 or improvement of signs and symptoms of visceral VZV), to complete a 10- to 14-day course (BIII).

ARN

• Acyclovir 10 mg/kg IV every 8 hours for 10–14 days, followed by valacyclovir 1g PO three times a day for >14 weeks (AIII), plus
• Intravitreal ganciclovir 2 mg/0.05 mL twice weekly for 1–‍2 doses (BIII)

PORN

• Acyclovir 10 mg/kg IV every 8 hours or ganciclovir 5 mg/kg IV every 12 hours (AIII), plus
• ≥1 intravitreal antiviral injection: ganciclovir 2 mg/0.05 mL or foscarnet 1.2 mg/0.05 mL twice weekly (AIII)
• Initiate or optimize ART (AIII)

Primary Varicella Infection (Chickenpox)

Uncomplicated Cases (for 5–7 Days)

• Acyclovir 800 mg PO five times a day (BII)

Herpes Zoster (Shingles)

Acute Localized Dermatomal

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

In managing VZV of the eyes, consultation with an ophthalmologist experienced in management of VZV retinitis is strongly recommended (AIII).

Duration of therapy for VZV retinitis is not well defined, and should be determined based on clinical, virologic, and immunologic responses and ophthalmologic responses.

Optimization of ART is recommended for serious and difficult-to-treat VZV infections (e.g., retinitis, encephalitis) (AIII).

In patients with herpes zoster ophthalmicus who have stromal keratitis and anterior uveitis, topical corticosteroids to reduce inflammation may be necessary. The role of ART has not been established in these cases.

^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.

^c This 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).

^d Many 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.

^e Given 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; 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; COBI = cobicistat; CrCl = creatinine clearance; CSF = cerebrospinal fluid; DAA = direct-acting antiviral; DOT = directly observed therapy; DRV = darunavir; DS = double strength; EMB = ethambutol; 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; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HD = hemodialysis; ICP = intracranial pressure; IDSA = Infectious Diseases Society of America; IL-6 = interleukin-6; IM = intramuscular; INH = isoniazid; IRIS = immune reconstitution inflammatory syndrome; IRU = immune reconstitution uveitis; IV = intravenous; LFA = lateral flow assay; LP = lumbar puncture; MIC = minimum inhibitory concentration; MSM = men who have sex with men; NSAID = nonsteroidal anti-‍inflammatory drugs; PaO₂ = partial pressure of oxygen; PCP = Pneumocystis pneumonia; PCR = polymerase chain reaction; PO = oral; PORN = progressive outer retinal necrosis; PZA = pyrazinamide; RFB = rifabutin; RIF = rifampin; RPT = rifapentine; SMX = sulfamethoxazole; SQ = subcutaneous; SS = single strength; STR = single-tablet regimen; SVR = sustained virologic response; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; TMP = trimethoprim; VIGIV = vaccinia immune globulin intravenous