Comparative efficacy and safety of treatment regimens for Pneumocystis jirovecii pneumonia in people living with HIV - A systematic review and network meta-analysis of randomized controlled trials
Abstract
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in people living with HIV (PWH) who have low CD4 counts. Despite its side effects, trimethoprim-sulfamethoxazole (TMP-SMX) is currently considered the primary treatment for PCP.
OBJECTIVES
To compare the efficacy (treatment-failure and mortality) and tolerability (treatment change) of PCP treatment-regimens with a frequentist network meta-analysis (NMA).
DATA SOURCES
Embase, MEDLINE, and CENTRAL from inception to February 3, 2024.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs) of at least two PCP treatment regimens.
PARTICIPANTS
PWH.
INTERVENTIONS
Treatment regimens for PCP compared head-to-head.
ASSESSMENT OF RISK-OF-BIAS
Cochrane risk-of-bias tool for RCTs (RoB2) DATA SYNTHESIS: Title, abstract, and full-text screening, along with data extraction, were conducted by two independent reviewers. Data on PCP treatment-failure, all-cause mortality, and discontinuation due to toxicity were pooled and ranked.
RESULTS
Fourteen RCTs conducted between 1983 and 1996 included 1,788 participants across 27 treatment-arms. No regimen showed statistically significant superiority over TMP-SMX in direct comparison. In the network meta-analysis, Clindamycin/Primaquine ranked best (surface-under-the-cumulative-ranking-curve, 0.8), followed by IV Pentamidine (0.8) and TMP-SMX (0.8) regarding treatment-failure. Regarding all-cause-mortality, TMP-SMX was superior to atovaquone in…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,788 participants or records.
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