Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire:: a randomised trial

Background In sub-Saharan Africa, various bacterial diseases occur before pneumocystosis or toxoplasmosis in the course of HIV-1 infection, and are major causes of morbidity and mortality. We did a randomised, double blind, placebo-controlled clinical trial at community-health centres in Abidjan, Cote d'Ivoire, to assess the efficacy of trimethoprim-sulphamethoxazole (co-trimoxazole) chemoprophylaxis at early stages of HIV-1 infection. Method 843 HIV-infected patients were screened and 545 enrolled in the study. Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo. The primary outcome was the occurrence of severe clinical events, defined as death or hospital admission irrespective of the cause. Analyses were by intention to treat. Findings Four of the randomised patients were excluded (positive for HIV-2 only). 120 severe events occurred among 271 patients in the co-trimoxazole group and 198 among 270 in the placebo group. Significantly fewer patients in the co-trimoxazole group than in the placebo group had at least one severe event (84 vs 124); the probability of remaining free of severe events was 63.7% versus 45.8% (hazard ratio 0.57 [95% CI 0.43-0.75], p=0.0001) and the benefit was apparent in all subgroups of initial CD4-cell count. Survival did not differ between the groups (41 vs 46 deaths, p=0.51). Cotrimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients ( vs 26 in the placebo group). Interpretation Patients who might benefit from cotrimoxazole trimoxazole could be recruited on clinical criteria in community clinics without knowing the patients CD4-cell count. This affordable measure will enable quick public-health intervention, while monitoring bacterial susceptibility and haematological tolerance.