Randomised, placebo-controlled trial to evaluate co-trimoxazole to reduce mortality and morbidity in HIV-infected post-natal women in Zambia (TOPAZ)

Abstract

To evaluate the role of prophylactic trimethoprim-sulfamethoxazole (co-trimoxazole) antibacterial prophylaxis in reducing morbidity and mortality in HIV-infected post-natal women in southern Africa. Double-blind placebo-controlled trial. HIV-infected women with WHO stage 2 or 3 HIV disease who had recently delivered in the Department of Obstetrics and Gynaecology at the University Teaching Hospital, Lusaka, Zambia were randomised to receive daily co-trimoxazole (cotox) or matched placebo daily for the duration of the trial. Participants were followed up for a minimum of 1 year. Primary outcome measures were mortality from any cause or hospital admission and serious adverse events. Of 600 women randomised, follow-up information was available from 355 (180 cotox, 175 placebo) participants. Thirty-six (17 cotox, 19 placebo) women died during the trial, and another 11 (5 cotox, 6 placebo) were admitted to hospital. There was no significant difference in the combined event rates between the two treatment arms: HR = 0.82, 95% CI (0.46, 1.45), P = 0.49; morbidity was reduced over a range of symptoms. Secondary analyses of the outcome in babies indicated some evidence of reduced mortality in those whose mothers were allocated cotox. Follow-up rates were poor; there was no evidence that co-trimoxazole prophylaxis reduced mortality or hospital admission rates, although fewer symptoms were reported in the cotox arm. Cotox was safe and well tolerated.