Background Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. Methods Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1·5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. Findings Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0·54 [95% CI 0·35-0·84], p=0·006) and lower rates of malaria (multivariate incidence rate ratio 0·28 [0·19-0·40], p<0·0001), diarrhoea (0·65 [0·53-0·81], p<0·0001), and hospital admission (0·69 [0·48-0·98], p=0·04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per μL, p<0·0001), and the annual rate of increase in viral load was lower (0·08 vs 0·90 log10 copies per mL, p=0·01). Interpretation Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.
