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Randomized Controlled Trial
. 2008 Jul 10;337:a257.
doi: 10.1136/bmj.a257.

Role of Co-Trimoxazole Prophylaxis in Reducing Mortality in HIV Infected Adults Being Treated for Tuberculosis: Randomised Clinical Trial

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Free PMC article
Randomized Controlled Trial

Role of Co-Trimoxazole Prophylaxis in Reducing Mortality in HIV Infected Adults Being Treated for Tuberculosis: Randomised Clinical Trial

Andrew J Nunn et al. BMJ. .
Free PMC article

Abstract

Objective: To assess the impact of prophylactic oral co-trimoxazole in reducing mortality in HIV positive Zambian adults being treated for pulmonary tuberculosis.

Design: Double blind placebo controlled randomised clinical trial.

Participants: Two groups of antiretroviral treatment naive adults with HIV infection: patients newly diagnosed as having tuberculosis and receiving tuberculosis treatment either for the first time or for retreatment after relapse; previously treated patients not receiving treatment.

Intervention: Oral co-trimoxazole or matching placebo daily. Primary outcome measures Time to death and occurrence of serious adverse events related to study drug.

Results: 1003 patients were randomised: 835 (416 co-trimoxazole, 419 placebo) were receiving treatment for tuberculosis, 762 (376 co-trimoxazole, 386 placebo) of them newly diagnosed previously untreated patients and 73 (40 co-trimoxazole, 33 placebo) receiving a retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) were not on treatment but had received treatment in the past. Of 835 participants receiving tuberculosis treatment, follow-up information was available for 757, with a total of 1012.6 person years of follow-up. A total of 310 (147 co-trimoxazole, 163 placebo) participants died, corresponding to death rates of 27.3 and 34.4 per 100 person years. In the Cox regression analysis, the hazard ratio for death (co-trimoxazole:placebo) was 0.79 (95% confidence interval 0.63 to 0.99). The effect of co-trimoxazole waned with time, possibly owing to falling adherence levels; in a per protocol analysis based on patients who spent at least 90% of their time at risk supplied with study drug, the hazard ratio was 0.65 (0.45 to 0.93).

Conclusions: Prophylaxis with co-trimoxazole reduces mortality in HIV infected adults with pulmonary tuberculosis. Co-trimoxazole was generally safe and well tolerated.

Trial registration: Current Controlled Trials ISRCTN15281875.

Conflict of interest statement

Competing interests: None declared.

Figures

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Fig 1 Trial profile. *Includes 73 (40 co-trimoxazole, 33 placebo) participants who received a retreatment regimen
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Fig 2 Time to death according to trial drug (based on 835 HIV positive patients newly diagnosed as having, and being treated for, tuberculosis)

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