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


RESULTS
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).


CONCLUSIONS
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.
CDC-Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, National Center for Infectious Diseases; Centers for Disease Control and Prevention, Atlanta, GA, USA. jhm7@cdc.gov
Jonathan
J
Mermin
John
J
Lule
John Paul
JP
Ekwaru
Samuel
S
Malamba
Robert
R
Downing
Ray
R
Ransom
Frank
F
Kaharuza
David
D
Culver
Francis
F
Kizito
Rebecca
R
Bunnell
Aminah
A
Kigozi
Damalie
D
Nakanjako
Winnie
W
Wafula
Robert
R
Quick
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000293:Adolescent; D000328:Adult; D000553:Ambulatory Care; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D019072:Antibiotic Prophylaxis; D000962:Antimalarials / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D002648:Child; D003967:Diarrhea / Q000517:prevention & control; D004352:Drug Resistance, Microbial; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000821:virology; D015497:HIV-1; D006760:Hospitalization; D006801:Humans; D008288:Malaria / Q000150:complications / Q000517:prevention & control; D008297:Male; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
D000890:Anti-Infective Agents; D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination