HIV/AIDS management: Trial demonstrates importance of cotrimoxazole prophylaxis in malaria-endemic regions

Cotrimoxazole (CTX) discontinuation is inferior to CTX continuation among ART-treated, immune-reconstituted HIV-infected adults living in a malaria-endemic region, according to a trial published this week in PLOS Medicine by Christina Polyak at the Walter Reed Army Institute of Research and University of Washington, U.S., and colleagues. These trial findings were important for December 2014 WHO guidelines recommending that CTX prophylaxis be continued regardless of CD4 cell count or HIV/AIDS clinical stage in settings where malaria is endemic and/or severe bacterial infections are common.

The trial enrolled 500 HIV-infected adults living in a malaria-endemic region of Kenya who had been treated with ART for ?18 months, who had a CD4 count of >350 cells/mm3, and who were taking CTX. After 12 months of follow-up, the combined rate of morbidity events (malaria, pneumonia, and diarrhea) and non-trauma mortality events was significantly higher in the CTX discontinuation arm than in the CTX continuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001). The difference in this primary outcome between the trial arms was driven by malaria morbidity—there were 33 cases of malaria in the CTX discontinuation arm but only one case in the CTX continuation arm.

Study limitations included lack of blinding and statistical constraints from lower than expected incidence of morbidity. However, analyses were strengthened by 98% retention rates in both arms. The authors state, "Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence."