Daily Co-Trimoxazole Prophylaxis in Severely Immunosuppressed HIV-Infected Adults in Africa Started on Combination Antiretroviral Therapy: An Observational Analysis of the DART Cohort

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dc.contributor.authorWalker, A.S.
dc.contributor.authorMunderi, P.
dc.contributor.authorKatabira, E.
dc.contributor.authorMugyenyi, P.
dc.contributor.authorSsali, F.
dc.contributor.authorHakim, J.
dc.contributor.authorBabiker, A. G.
dc.date.accessioned2023-02-06T18:52:49Z
dc.date.available2023-02-06T18:52:49Z
dc.date.issued2010
dc.description.abstractCo-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. 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 μL. 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. 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 μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68]. 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.en_US
dc.identifier.citationWalker, A. S., Ford, D., Gilks, C. F., Munderi, P., Ssali, F., Reid, A., ... & Babiker, A. G. (2010). Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort. The Lancet, 375(9722), 1278-1286.https://doi.org/10.1016/S0140-6736(10)60057-8en_US
dc.identifier.issn0140-6736
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/7607
dc.language.isoenen_US
dc.publisherThe Lanceten_US
dc.subjectCo-Trimoxazoleen_US
dc.subjectHIV-Infecteden_US
dc.subjectAdultsen_US
dc.subjectDARTen_US
dc.titleDaily Co-Trimoxazole Prophylaxis in Severely Immunosuppressed HIV-Infected Adults in Africa Started on Combination Antiretroviral Therapy: An Observational Analysis of the DART Cohorten_US
dc.typeArticleen_US
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