Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Updated

Feb. 09, 2021

Reviewed

Feb. 09, 2021

Tables

Table 4. Indications for Discontinuing and Restarting Opportunistic Infection Prophylaxis in HIV-Infected Adults and Adolescents

Table 4. Indications for Discontinuing and Restarting Opportunistic Infection Secondary Prophylaxis or Chronic Maintenance in HIV-Infected Adults and Adolescents
Opportunistic Infection	Indication for Discontinuing Primary Prophylaxis	Indication for Restarting Primary Prophylaxis	Indication for Discontinuing Secondary Prophylaxis/Chronic Maintenance Therapy	Indication for Restarting Secondary Prophylaxis/Chronic Maintenance
Bacterial Enteric Infections: Salmonellosis	Not applicable	Not applicable	Resolution of Salmonella infection and after response to ART with sustained viral suppression and CD4 counts >200 cells/µL (CII)	No recommendation
Bartonellosis	Not applicable	Not applicable	Received at least 3–4 months of treatment, and CD4 count >200 cells/µL for ≥6 months (CIII) Some specialists would only discontinue therapy if Bartonella titers have also decreased by four-fold (CIII).	No recommendation
Candidiasis (Mucocutaneous)	Not applicable	Not applicable	If used, reasonable to discontinue when CD4 count >200 cells/µL (AIII).	No recommendation
Coccidioidomycosis	CD4 count ≥250 cells/µL with viral suppression on ART (BIII)	Restart at CD4 count <250 cells/µL (BIII)	Only for patients with mild to moderate pneumonia (AII): Clinically responded to 3-6 months of antifungal therapy, with CD4 count >250 cells/mm3, and viral suppression on ART. Should continue monitoring for recurrence with serial chest radiographs and coccidioidal serology. For patients with diffuse pulmonary (BIII), disseminated non-meningeal (BIII): Continue therapy for at least 12 months or longer; discontinuation based on clinical and serologic response and in consultation with experts. For patients with meningeal diseases (AII): Suppressive therapy should be continued indefinitely.	No recommendation
Cryptococcal Meningitis	Not applicable	Not applicable	If the following criteria are fulfilled (BII): Completed initial (induction and consolidation) therapy, and Received at least 1 year of maintenance therapy, and Remain asymptomatic of cryptococcal infection, and CD4 count ≥100 cells/µL for >3 months, and with suppressed plasma HIV RNA in response to ART	CD4 count <100 cells/µL (AIII)
Cystoisosporiasis (Formerly Isosporiasis)	Not applicable	Not applicable	Sustained increase in CD4 count to >200 cells/µL for >6 months in response to ART and without evidence of I. belli infection (BIII)	No recommendation
Cytomegalovirus Retinitis	Not applicable	Not applicable	CMV treatment for at least 3 to 6 months; and with CD4 count >100 cells/µL for >3 to 6 months in response to ART (AII). Therapy should be discontinued only after consultation with an ophthalmologist, taking into account anatomic location of lesions, vision in the contralateral eye, and feasibility of regular ophthalmologic monitoring. Routine (i.e., every 3 months) ophthalmologic follow-up is recommended after stopping therapy for early detection of relapse or immune restoration uveitis, and then periodically after sustained immune reconstitution (AIII).	CD4 count <100 cells/µL (AIII)
Histoplasmosis	On ART, with CD4 count >150 cells/mm³ and undetectable HIV-1 viral load for 6 months (BIII)	For patients at high risk of acquiring histoplasmosis, restart if CD4 count falls to <150 cells/mm³ (CIII)	If the Following Criteria (AI) are Fulfilled: Received azole therapy for >1 year, and Negative fungal blood cultures, and Serum or urine Histoplasma antigen below the level of quantification, and Undetectable HIV viral load, and CD4 count ≥150 cells/mm³ for ≥6 months in response to ART	CD4 count <150 cells/mm³ (BIII)
Leishmaniasis: Visceral (and possibly cutaneous leishmaniasis in immunocompromised patients with multiple relapses)	Not applicable	Not applicable	There is no consensus regarding when to stop secondary prophylaxis. Some investigators suggest that therapy can be stopped if CD4 count increases to >200 to 350 cells/µL for 3–6 months in response to ART, but others suggest that therapy should be continued indefinitely.	No recommendation
Microsporidiosis	Not applicable	Not applicable	No signs and symptoms of non-ocular (BIII) or ocular (CIII) microsporidiosis and CD4 count >200 cells/µL for >6 months in response to ART.	No recommendation
Mycobacterium avium Complex Disease	Initiation of effective ART (AI)	CD4 count <50 cells/mm³: only if not on fully suppressive ART (AIII)	If the following criteria are fulfilled (AI): Completed ≥12 months of therapy, and No signs and symptoms of MAC disease, and Have sustained (>6 months) CD4 count >100 cells/mm³ in response to ART.	CD4 count <100 cells/mm³ (AIII)
Pneumocystis Pneumonia	CD4 count increased from <200 to >200 cells/mm³ for >3 months in response to ART (AI) Can consider when CD4 count is 100–200 cells/mm³ if HIV RNA remains below limits of detection for ≥3 months–6 months (BII).	CD4 count <100 cells/mm³ (AIII) CD4 count 100–200 cells/mm³ and HIV RNA above detection limit of the assay (AIII).	CD4 count increased from <200 cells/mm³ to >200 cells/mm³ for >3 months in response to ART (BII) Can consider when CD4 count is 100–200 cells/mm³ if HIV RNA remains below limits of detection for ≥3 months–6 months (BII). If PCP occurs at a CD4 count >200 cells/mm³ while not on ART, discontinuation of prophylaxis can be considered once HIV RNA levels are suppressed to below limits of detection for ≥3 months–6 months (CIII). If PCP occurs at a CD4 count >200 cells/mm³ while on ART, continue PCP prophylaxis for life, regardless of how high the CD4 cell count rises as a consequence of ART (BIII).	CD4 count <100 cells/mm³ (AIII) CD4 count 100–200 cells/mm³ and with HIV RNA above detection limit of the assay (AIII).
Talaromycosis (Penicilliosis)	CD4 count >100 cells/mm³ for >6 months in response to ART (BII) or If achieved sustained HIV viral suppression for >6 months (BIII)	CD4 count <100 cells/mm³ (BIII)—if patient is unable to have ART, or has treatment failure without access to effective ART options, and still resides in or travels to the endemic area	CD4 count >100 cells/mm³ for ≥6 months in response to ART (BII) or If achieved sustained HIV viral suppression for >6 months (BIII)	CD4 count <100 cells/mm³ (BIII)
Toxoplasma gondii Encephalitis	CD4 count increased to >200 cells/µL for >3 months in response to ART (AI) Can consider when CD4 count 100-200 cells/µL if HIV RNA remain below limits of detection for at least 3-6 months (BII)	CD4 count <100 cells/µL (AIII). CD4 count 100-200 cells/ µL and with HIV RNA above detection limit of the assay (AIII).	Successfully completed initial therapy, receiving maintenance therapy and remain free of signs and symptoms of TE, and CD4 count >200 cells/µL for >6 months in response to ART (BI).	CD4 count <200 cells/ µL (AIII)
Key to Acronyms: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte cell; CMV = cytomegalovirus; MAC = Mycobacterium avium complex; PCP = Pneumocystis pneumonia; TE = Toxoplasma encephalitis Evidence Rating: Strength of Recommendation: A: Strong recommendation for the statement B: Moderate recommendation for the statement C: Optional recommendation for the statement Quality of Evidence for the Recommendation: I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints II: One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes III: Expert opinion In cases where there are no data for the prevention or treatment of an OI based on studies conducted in HIV-infected populations, but data derived from HIV-uninfected patients exist that can plausibly guide management decisions for patients with HIV/AIDS, the data will be rated as III but will be assigned recommendations of A, B, C depending on the strength of recommendation.

Tables

Table 4. Indications for Discontinuing and Restarting Opportunistic Infection Prophylaxis in HIV-Infected Adults and Adolescents

Table 4. Indications for Discontinuing and Restarting Opportunistic Infection Secondary Prophylaxis or Chronic Maintenance in HIV-Infected Adults and Adolescents
Opportunistic Infection	Indication for Discontinuing Primary Prophylaxis	Indication for Restarting Primary Prophylaxis	Indication for Discontinuing Secondary Prophylaxis/Chronic Maintenance Therapy	Indication for Restarting Secondary Prophylaxis/Chronic Maintenance
Bacterial Enteric Infections: Salmonellosis	Not applicable	Not applicable	Resolution of Salmonella infection and after response to ART with sustained viral suppression and CD4 counts >200 cells/µL (CII)	No recommendation
Bartonellosis	Not applicable	Not applicable	Received at least 3–4 months of treatment, and CD4 count >200 cells/µL for ≥6 months (CIII) Some specialists would only discontinue therapy if Bartonella titers have also decreased by four-fold (CIII).	No recommendation
Candidiasis (Mucocutaneous)	Not applicable	Not applicable	If used, reasonable to discontinue when CD4 count >200 cells/µL (AIII).	No recommendation
Coccidioidomycosis	CD4 count ≥250 cells/µL and with viral suppression while on ART (CIII)	Restart at CD4 count <250 cells/µL (BIII)	Only for patients with focal coccidioidal pneumonia (AII): Clinically responded to ≥ 6 months antifungal therapy, with CD4 count ≥250 cells/mm³, and with viral suppression while on ART. Should continue monitoring for recurrence with serial chest radiographs and coccidioidal serology every 6-12 months. For patients with diffuse pulmonary (BIII), disseminated non-meningeal (BIII): Therapy is at least 12 months and usually much longer; discontinuation is dependent on clinical and serological response and should be made in consultation with experts For meningeal diseases (AII): Suppressive therapy should be continued indefinitely, even with increase in CD4 count on ART.	No recommendation
Cryptococcal Meningitis	Not applicable	Not applicable	If the following criteria are fulfilled (BII): Completed initial (induction and consolidation) therapy, and Received at least 1 year of maintenance therapy, and Remain asymptomatic of cryptococcal infection, and CD4 count ≥100 cells/µL for >3 months, and with suppressed plasma HIV RNA in response to ART	CD4 count <100 cells/µL (AIII)
Cystoisosporiasis (Formerly Isosporiasis)	Not applicable	Not applicable	Sustained increase in CD4 count to >200 cells/µL for >6 months in response to ART and without evidence of I. belli infection (BIII)	No recommendation
Cytomegalovirus Retinitis	Not applicable	Not applicable	CMV treatment for at least 3 to 6 months; and with CD4 count >100 cells/µL for >3 to 6 months in response to ART (AII). Therapy should be discontinued only after consultation with an ophthalmologist, taking into account anatomic location of lesions, vision in the contralateral eye, and feasibility of regular ophthalmologic monitoring. Routine (i.e., every 3 months) ophthalmologic follow-up is recommended after stopping therapy for early detection of relapse or immune restoration uveitis, and then periodically after sustained immune reconstitution (AIII).	CD4 count <100 cells/µL (AIII)
Histoplasmosis	On ART, with CD4 count >150 cells/mm³ and undetectable HIV-1 viral load for 6 months (BIII)	For patients at high risk of acquiring histoplasmosis, restart if CD4 count falls to <150 cells/mm³ (CIII)	If the Following Criteria (AI) are Fulfilled: Received azole therapy for >1 year, and Negative fungal blood cultures, and Serum or urine Histoplasma antigen below the level of quantification, and Undetectable HIV viral load, and CD4 count ≥150 cells/mm³ for ≥6 months in response to ART	CD4 count <150 cells/mm³ (BIII)
Leishmaniasis: Visceral (and possibly cutaneous leishmaniasis in immunocompromised patients with multiple relapses)	Not applicable	Not applicable	There is no consensus regarding when to stop secondary prophylaxis. Some investigators suggest that therapy can be stopped if CD4 count increases to >200 to 350 cells/µL for 3–6 months in response to ART, but others suggest that therapy should be continued indefinitely.	No recommendation
Microsporidiosis	Not applicable	Not applicable	No signs and symptoms of non-ocular (BIII) or ocular (CIII) microsporidiosis and CD4 count >200 cells/µL for >6 months in response to ART.	No recommendation
Mycobacterium avium Complex Disease	Initiation of effective ART (AI)	CD4 count <50 cells/mm³: only if not on fully suppressive ART (AIII)	If the following criteria are fulfilled (AI): Completed ≥12 months of therapy, and No signs and symptoms of MAC disease, and Have sustained (>6 months) CD4 count >100 cells/mm³ in response to ART.	CD4 count <100 cells/mm³ (AIII)
Pneumocystis Pneumonia	CD4 count increased from <200 to >200 cells/mm³ for >3 months in response to ART (AI) Can consider when CD4 count is 100–200 cells/mm³ if HIV RNA remains below limits of detection for ≥3 months–6 months (BII).	CD4 count <100 cells/mm³ (AIII) CD4 count 100–200 cells/mm³ and HIV RNA above detection limit of the assay (AIII).	CD4 count increased from <200 cells/mm³ to >200 cells/mm³ for >3 months in response to ART (BII) Can consider when CD4 count is 100–200 cells/mm³ if HIV RNA remains below limits of detection for ≥3 months–6 months (BII). If PCP occurs at a CD4 count >200 cells/mm³ while not on ART, discontinuation of prophylaxis can be considered once HIV RNA levels are suppressed to below limits of detection for ≥3 months–6 months (CIII). If PCP occurs at a CD4 count >200 cells/mm³ while on ART, continue PCP prophylaxis for life, regardless of how high the CD4 cell count rises as a consequence of ART (BIII).	CD4 count <100 cells/mm³ (AIII) CD4 count 100–200 cells/mm³ and with HIV RNA above detection limit of the assay (AIII).
Talaromycosis (Penicilliosis)	CD4 count >100 cells/mm³ for >6 months in response to ART (BII) or If achieved sustained HIV viral suppression for >6 months (BIII)	CD4 count <100 cells/mm³ (BIII)—if patient is unable to have ART, or has treatment failure without access to effective ART options, and still resides in or travels to the endemic area	CD4 count >100 cells/mm³ for ≥6 months in response to ART (BII) or If achieved sustained HIV viral suppression for >6 months (BIII)	CD4 count <100 cells/mm³ (BIII)
Toxoplasma gondii Encephalitis	CD4 count increased to >200 cells/µL for >3 months in response to ART (AI) Can consider when CD4 count 100-200 cells/µL if HIV RNA remain below limits of detection for at least 3-6 months (BII)	CD4 count <100 cells/µL (AIII). CD4 count 100-200 cells/ µL and with HIV RNA above detection limit of the assay (AIII).	Successfully completed initial therapy, receiving maintenance therapy and remain free of signs and symptoms of TE, and CD4 count >200 cells/µL for >6 months in response to ART (BI).	CD4 count <200 cells/ µL (AIII)
Key to Acronyms: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte cell; CMV = cytomegalovirus; MAC = Mycobacterium avium complex; PCP = Pneumocystis pneumonia; TE = Toxoplasma encephalitis Evidence Rating: Strength of Recommendation: A: Strong recommendation for the statement B: Moderate recommendation for the statement C: Optional recommendation for the statement Quality of Evidence for the Recommendation: I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints II: One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes III: Expert opinion In cases where there are no data for the prevention or treatment of an OI based on studies conducted in HIV-infected populations, but data derived from HIV-uninfected patients exist that can plausibly guide management decisions for patients with HIV/AIDS, the data will be rated as III but will be assigned recommendations of A, B, C depending on the strength of recommendation.

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