Effects of concurrent exposure to antiretrovirals and cotrimoxazole prophylaxis among HIV-exposed, uninfected infants

BACKGROUND:Given the potential of Cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with ARV agents that have overlapping toxicity profiles. METHODS:We used data from the Breastfeeding, Antiretrovirals and Nutrition-BAN study (2004–2010) to evaluate the association of CPT and ARV with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2,006 HEU infants in Lilongwe, Malawi. Hazards of severe outcomes (anemia, neutropenia, and elevated alanine aminotransferase), as defined by the National Institutes of Health, were compared using Cox regression models according to time-varying CPT (implemented June 2006), ARV treatment arm (maternal triple ARV, infant nevirapine, or none during six months of breastfeeding) and their interaction. The effects of these treatments on hemoglobin, neutrophil and alanine aminotransferase levels were assessed using linear mixed models. RESULTS:In Cox models, CPT was associated with an increase in severe neutropenia (Hazard ratio, HR1.97 [1.01, 3.86]) and a decrease in severe anemia (HR0.65 [0.48, 0.88]). Interactions between CPT and ARV were not significant. By 36 weeks, there was a significant association of CPT with increased hemoglobin levels regardless of ARV exposure. CONCLUSIONS:In addition to expected associations with increased hazard of severe neutropenia and decreased neutrophil count, CPT was associated with reduced hazard of severe anemia and higher infant blood hemoglobin. This provides further support for CPT use in HEU infants in malaria-endemic resource-limited settings where anemia is prevalent.