Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: A systematic review and network meta-analysis of randomized controlled trials



Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.


To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.

Methods: Data sources

Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.

Study eligibility criteria

Comparative randomized controlled trials (RCTs).




Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.

Assessment of risk of bias

Cochrane risk-of-bias tool for RCTs 2.

Methods of data synthesis

Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.


A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36–0.83) and AP (RR = 0.53; 95% CI, 0.36–0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64–0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01–1.54) and AP (7.20; 95% CI, 5.37–9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.


TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.


Prosty C, Katergi K, Sorin M, Rjeily MB, Butler-Laporte G, McDonald EG, Lee TC




  • Epidemiology and Determinants of Health
    • Epidemiology
  • Population(s)
    • General HIV+ population
  • Prevention, Engagement and Care Cascade
    • Prevention
  • Prevention
    • Biomedical interventions
  • Co-infections
    • Other


Abstract/Full paper

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