by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
April 4, 2019
Changes to the Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. Updated March 28, 2019.
Pneumocystis pneumonia (PCP) once common in persons with HIV infection is caused by the fungus Pneumocystis jirovecii. Previously referred to as Pneumocystis carinii, this species is now known to only infect rats. Pneumocystis jirovecii is the species that infects humans but the abbreviation “PCP” is still commonly used. Infection with P. jirovecii usually occurs in early childhood and about 60% of healthy children have antibodies to P. jirovecii by age 4 years. Disease in patients with PCP may represent reactivation of latent infection or new acquisition of the pathogen. The incidence of PCP has declined significantly over the past 10 years or so due to widespread use of PCP prophylaxis and most importantly antiretroviral therapy (ART). Most cases of PCP now occur in patients who are either unaware of their HIV infection, not taking ART or have more severe immunosuppression (CD4 counts <100 cells/mm3) despite ART.
Indication for Primary Prophylaxis
HIV-infected adults and adolescents with a CD4 count <200 cells/mm3 should receive chemoprophylaxis against PCP (AI) Those with a CD4 cell percentage <14% should also be considered for PCP prophylaxis (BII). Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended agent for PCP prevention (AI). The preferred regimen is one double-strength (DS) TMP-SMX tablet daily (AI). This dose is also protective against toxoplasmosis and other respiratory bacterial pathogens. One single-strength tablet daily is also effective and is often better tolerated than the DS (AI). One DS tablet three times weekly is also acceptable dosing (BI). For patients unable to tolerate TMP-SMX, alternative regimens are dapsone (BI), dapsone plus pyrimethamine plus leucovorin (BI),0 aerosolized pentamidine (BI), and atovaquone (BI).
Discontinuing Primary Prophylaxis
Primary prophylaxis can be discontinued in patients who have an increase in CD4 counts to >200 cells/mm3 for at least 3 months while on ART (AI). This recommendation is supported by both observation data and randomized trials. In these studies, at time of discontinuation of prophylaxis, median CD4 count was >300 cells/mm3. Most subjects also had a CD4 cell percentage ≥14% and sustained viral suppression. These studies were published almost 20 years ago. Benefits to stopping TMP-SMX including reduction of pill burden, cost, toxicity, drug-drug interactions, and selection of drug-resistant pathogens. Prophylaxis should be reintroduced if the patient’s CD4 count decreases to <200 cells/mm3 (AIII).
A combined analysis of newer data from European cohorts, a small RCT, and case series found a low incidence of PCP in patients with CD4 counts between 100 cells/mm3 and 200 cells/mm3, who were receiving ART and had HIV plasma viral loads <50 to 400 copies/mL, and who had stopped or never received PCP prophylaxis. These data suggest that both primary and secondary PCP prophylaxis can be safely discontinued in patients with CD4 counts between 100 cells/mm3 to 200 cells/mm3 and HIV plasma RNA levels below limits of detection. Data on which to base specific drug recommendations are not available however one reasonable approach would be to stop primary prophylaxis in patients with CD4 counts of 100 cells/mm3 to 200 cells/mm3 if HIV plasma RNA levels remain below limits of detection for ≥3 months to 6 months (BII).
Author’s comment: This new recommendation is a significant change from what we have been doing for many years regarding discontinuation of pneumocystis prophylaxis. Prophylaxis for persons with a CD4 count < 200 has also been a core performance measure from HRSA for Ryan White-funded programs. This specific core measure should likely be changed or perhaps eliminated in the future. In recent years most HIV providers have learned that the best prophylaxis against all opportunistic infections is ART.
Readers are referred to Reference #1 below section B for the complete discussion on the prevention and treatment of Pneumocystis pneumonia.
Indications for Initiating Primary Prophylaxis for PCP:
Indication for Discontinuing Primary Prophylaxis:
Indication for Restarting Primary Prophylaxis:
CD4 count 100–200 cells/mm3 and HIV RNA above detection limit of the assay used (AIII)
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