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, Côte 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). Co-trimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients (vs 26 in the placebo group).
Interpretation: Patients who might benefit from co-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.