Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial

doi:10.1136/bmj.a257

Published 10 July 2008, doi:10.1136/bmj.a257
Cite this as: BMJ 2008;337:a257

Research

Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial

Andrew J Nunn, associate director ¹, Peter Mwaba, director and consultant physician², Chifumbe Chintu, professor of paediatrics ², Alwyn Mwinga, senior scientist², Janet H Darbyshire, director¹, Alimuddin Zumla, professor and director³, for the UNZA-UCLMS Project LUCOT Collaboration

¹ Medical Research Council Clinical Trials Unit, London NW1 2DA, ² University Teaching Hospital, UNZA School of Medicine, Box 50110, Lusaka, Zambia, ³ University College London, Centre for Infectious Diseases and International Health, London W1T 4JF

Correspondence to: A Nunn ajn{at}ctu.mrc.ac.uk

Objective To assess the impact of prophylactic oral co-trimoxazolein reducing mortality in HIV positive Zambian adults being treatedfor pulmonary tuberculosis.

Design Double blind placebo controlled randomised clinical trial.

Participants Two groups of antiretroviral treatment naive adultswith HIV infection: patients newly diagnosed as having tuberculosisand receiving tuberculosis treatment either for the first timeor for retreatment after relapse; previously treated patientsnot receiving treatment.

Intervention Oral co-trimoxazole or matching placebo daily.

Primary outcome measures Time to death and occurrence of seriousadverse 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 previouslyuntreated patients and 73 (40 co-trimoxazole, 33 placebo) receivinga retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) werenot on treatment but had received treatment in the past. Of835 participants receiving tuberculosis treatment, follow-upinformation was available for 757, with a total of 1012.6 personyears of follow-up. A total of 310 (147 co-trimoxazole, 163placebo) participants died, corresponding to death rates of27.3 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-trimoxazolewaned with time, possibly owing to falling adherence levels;in a per protocol analysis based on patients who spent at least90% of their time at risk supplied with study drug, the hazardratio was 0.65 (0.45 to 0.93).

Conclusions Prophylaxis with co-trimoxazole reduces mortalityin HIV infected adults with pulmonary tuberculosis. Co-trimoxazolewas generally safe and well tolerated.

Trial registration Current Controlled Trials ISRCTN15281875 [controlled-trials.com] .

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