Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort

Walker, A. S., Ford, D., Gilks, C. F., Munderi, P., Ssali, F., Reid, A., Katabira, E., Grosskurth, H., Mugyenyi, P., Hakim, J., Darbyshire, J. H., Gibb, D. M. and 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. Lancet, 375 9722: 1278-1286. doi:10.1016/S0140-6736(10)60057-8


Author Walker, A. S.
Ford, D.
Gilks, C. F.
Munderi, P.
Ssali, F.
Reid, A.
Katabira, E.
Grosskurth, H.
Mugyenyi, P.
Hakim, J.
Darbyshire, J. H.
Gibb, D. M.
Babiker, A. G.
Title Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
1474-547X
Publication date 2010-04
Year available 2010
Sub-type Article (original research)
DOI 10.1016/S0140-6736(10)60057-8
Open Access Status
Volume 375
Issue 9722
Start page 1278
End page 1286
Total pages 9
Place of publication London, United Kingdom
Publisher Lancet Publishing Group
Collection year 2010
Language eng
Formatted abstract
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 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.

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 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].

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. 
Keyword Trimethoprim Sulfamethoxazole Prophylaxis
Pneumocystis Carinii Pneumonia
Immune Activation
Early Mortality
Hiv 1 Infected Patients
Secondary Prophylaxis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
 
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