Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial

摘要

>Objective To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.>Design Non-blinded randomised control trial>Setting Tororo district, rural Uganda, an area of high malaria transmission intensity>Participants 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age>Intervention Co-trimoxazole prophylaxis from enrolment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n=185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old.>Main outcome measure Incidence of malaria, calculated as the number of antimalarial treatments per person year.>Results The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P=0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms.>Conclusions Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance.>Trial registration Clinical Trials