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

Abstract

SummaryBackground 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 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.

Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries

“…It has a broad-spectrum prophylactic action against common bacterial pathogens, Pneumocystis jirovecii (formerly Pneumocystis carinii) , and protozoa such as Plasmodium spp and Isospora belli. Randomised controlled trials (RCTs) 9,10 and studies with historical controls [11][12][13][14][15][16] in HIVinfected African adults consistently show signifi cant benefi ts in survival for those receiving co-trimoxazole prophylaxis. These improvements in survival have been accompanied by substantial reductions of severe disease events and the number of hospital admissions linked to invasive bacterial disease, pneumonia, malaria, and diarrhoea, although disease-specifi c benefi t has varied between studies.…”

“…17 Many of the studies showing benefi t have been in communities where in-vitro co-trimoxazole resistance to common bacterial isolates is already high. 14,[16][17][18] It is well recognised that P jirovecii is a common cause of pneumonia and death in HIV-infected infants. [19][20][21][22] The introduction of routine co-trimoxazole prophylaxis for infants at risk of HIV infection in several countries has been very eff ective in preventing P jirovecii pneumonia, which could in itself prevent a third to a half of all HIVrelated deaths in African infants.…”

“…Since then, several studies have shown that co-trimoxazole prophylaxis improves survival and reduces serious disease events even in areas of Africa where in-vitro cotrimoxazole resistance is common. [12][13][14][15][16][17] Furthermore, although resistance levels increase with time, as they have in Abidjan, this has not prevented the drug from being useful. 18 Co-trimoxazole's effi cacy against pneumocystis, isospora, and malaria might explain its favourable eff ects on morbidity and survival in endemic areas.…”

Utilization of a basic care and prevention package by HIV-infected persons in Uganda

“…Cotrimoxazole prophylaxis, which reduces mortality; decreases the risk of diarrhoea, malaria, and bacteremia; and potentially benefits CD4 cell count and viral load among people with HIV living in Africa (Badri, 2001;Castetbon, 2001;Mermin, 2004;Witkor, 1999). Cotrimoxazole prophylaxis has been recommended for daily use by adults and children with HIV by the Joint United Nations Program on HIV/ AIDS (UNAIDS) and the World Health Organization (WHO, 2006) and is recommended by the Ugandan Ministry of Health for all individuals living with HIV.…”

The use of readily available biomarkers to predict CD4 cell counts in HIV-infected individuals

“…22 A study evaluating the effect of co-trimoxazole for PJP prophylaxis in Uganda demonstrated that the number needed to treat (prophylaxis) per life saved was 2.6 in individuals with a CD4 cell count below 200 cells/mm 3 compared with 8.3 for all participants in the study. 23 Therefore despite the risk of misclassification of the immune status using this study's methods, when weighted against long waiting periods for measured CD4 count results in resource-limited settings, primary prophylaxis with co-trimoxazole may be advocated using this method due to the high mortality rate associated with PJP. Whilst early initiation of ART is imperative, as a practical indicator of ART initiation further prospective studies are required before the use of this method can be advocated.…”