Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda

Summary

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.

Introduction

Co-trimoxazole (trimethoprim-sulphamethoxazole) prophylaxis is routinely provided to people with AIDS in Europe and the USA.¹ It has been recommended for use in Africa on the basis of lower morbidity and mortality among people with HIV infection and AIDS,2, 3, 4, 5, 6, 7 but it is rarely used.⁸ Questions remain about the efficacy of co-trimoxazole in areas of high bacterial resistance, its relative usefulness among individuals with differing CD4-cell counts, and the mechanisms through which it exerts its effect.

Recent attention on HIV/AIDS care in Africa has focused on increasing access to antiretroviral medications. However, for many reasons, these drugs are currently not available to the majority of people with HIV/AIDS living in Africa. Co-trimoxazole prophylaxis might be a particularly useful intervention for people with no access to antiretroviral agents and for those with CD4-cell counts too high for antiretroviral therapy to be appropriate. Daily co-trimoxazole also lays the groundwork for medication adherence by the patient and the establishment of reliable drug distribution systems.

A recent randomised controlled trial in Senegal that was ended early found no beneficial effect of co-trimoxazole on mortality;⁹ further randomised trials have not been considered ethical. However, more information about the efficacy of co-trimoxazole prophylaxis in Africa is needed. To assess the efficacy of co-trimoxazole in preventing morbidity and mortality in an area with high rates of antimicrobial resistance to the drug combination, we undertook a prospective cohort study of co-trimoxazole prophylaxis in rural Uganda.