Updated
Reviewed
Apr. 14, 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 for ≥6 months (CIII) Restart at CD4 count <250 cells/µL (BIII)

Only for patients with focal coccidioidal pneumonia (AII):

  • Clinically responded to ≥12 months antifungal therapy, with CD4 count >250 cells/mm3, and receiving effective ART. 
  • Should continue monitoring for recurrence with serial chest radiographs and coccidioidal serology.

For patients with diffuse pulmonary (BIII), disseminated non-meningeal (BIII), or 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 antifungal therapy, and
  • Remain asymptomatic of cryptococcal infection, and
  • CD4 count ≥100 cells/µL, and with suppressed plasma HIV RNA in response to ART 
 CD4 count <100 cells/µL (AIII)
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)
Histoplasma capsulatum Infection 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)
Isospora belli Infection 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
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 for ≥6 months (CIII) Restart at CD4 count <250 cells/µL (BIII)

Only for patients with focal coccidioidal pneumonia (AII):

  • Clinically responded to ≥12 months antifungal therapy, with CD4 count >250 cells/mm3, and receiving effective ART. 
  • Should continue monitoring for recurrence with serial chest radiographs and coccidioidal serology.

For patients with diffuse pulmonary (BIII), disseminated non-meningeal (BIII), or 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 antifungal therapy, and
  • Remain asymptomatic of cryptococcal infection, and
  • CD4 count ≥100 cells/µL, and with suppressed plasma HIV RNA in response to ART 
 CD4 count <100 cells/µL (AIII)
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)
Histoplasma capsulatum Infection 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)
Isospora belli Infection 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
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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