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

Lancet. 2004 Oct 16-22;364(9443):1428-34. doi: 10.1016/S0140-6736(04)17225-5.

Abstract

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 microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) 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.

Publication types

  • Clinical Trial

MeSH terms

  • AIDS-Related Opportunistic Infections / prevention & control
  • Adolescent
  • Adult
  • Ambulatory Care
  • Anti-Infective Agents / administration & dosage*
  • Antibiotic Prophylaxis*
  • Antimalarials / administration & dosage
  • CD4 Lymphocyte Count*
  • Child
  • Diarrhea / prevention & control
  • Drug Resistance, Microbial
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / mortality
  • HIV Infections / virology
  • HIV-1*
  • Hospitalization
  • Humans
  • Malaria / complications
  • Malaria / prevention & control
  • Male
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage*
  • Uganda / epidemiology
  • Viral Load

Substances

  • Anti-Infective Agents
  • Antimalarials
  • Trimethoprim, Sulfamethoxazole Drug Combination