期刊
LANCET
卷 375, 期 9722, 页码 1278-1286出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0140-6736(10)60057-8
关键词
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资金
- UK Medical Research Council
- UK Department for International Development
- Rockefeller Foundation
- GlaxoSmithKline
- Gilead Sciences
- Boehringer-Ingelheim
- Abbott Laboratories
- MRC [G0600344, MC_U122886352, MC_U950080931] Funding Source: UKRI
- Medical Research Council [G0600344, MC_U950080931, MC_U122886352] Funding Source: researchfish
Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. Methods Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per mu L. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. Findings 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0.65, 95% CI 0.50-0.85; p=0.001). Mortality risk reduction on ART was substantial to 12 weeks (0.41, 0.27-0.65), sustained from 12-72 weeks (0.56, 0.37-0.86), but not evident subsequently (0-96, 0.63-1-45; heterogeneity p=0.02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0.74, 0.63-0.88; p=0.0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0.86, 0.69-1.07; p=0.17), CD4 cell count (difference vs non-users, 3 cells per mu L [-12 to 6]; p=0.50), or BMI (difference vs non-users, 0.04 kg/m(2) [-0-20 to 0.13); p=0.681. Interpretation Our results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks for all adults starting combination ART in Africa.
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