Time for new recommendations on cotrimoxazole prophylaxis for HIV-exposed infants in developing countries

Abstract

Background Pneumocystisjiroveci (formerly known as Pneumocystis carinii) pneumonia has been reported to be a leading cause of death in HIV-infected infants. In 2000 the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued recommendations on the use of cotrimoxazole (trimethoprim-sulfamethoxazole), as prophylaxis against Pneumocystis jiroveci for HIV-exposed infants. Cotrimoxazole is a broad-spectrum antimicrobial agent used to target a range of bacteria as well as some fungi and protozoa. These recommendations on cotrimoxazole prophylaxis emerged shortly after studies in Abidjan, Cote d'Ivoire, showed its impact on reducing morbidity in HIV-infected adults. However, the evidence of benefit in children was much weaker and consisted of positive impact in observational studies from the United States of America; an ecological study from Thailand that ascribed a decline in hospitalization cases of Pneumocystis jiroveci to an increased use of cotrimoxazole; and conflicting evidence from retrospective analyses of hospital data from three African studies. (1) Diagnosis of HIV in children aged less than 12 months is difficult as it requires the use of costly molecular diagnostics. Since it is not always possible to know which HIV-exposed infants are infected, the guidelines recommended that all HIV-exposed children should receive cotrimoxazole prophylaxis. More evidence Since the 2000 guidelines were published, further evidence on the effectiveness of cotrimoxazole prophylaxis against opportunistic infections in HIV-infected children emerged from the CHAP study, a randomized, placebo-controlled trial of cotrimoxazole in Zambia. (2) The study, which showed a significant impact on reducing mortality, included only HIV-infected children from 6 months to 14 years of age. Of note is that only 3% of the cohort was aged less than 12 months and the majority were symptomatic and had a CD4+ lymphocyte % New data While we reaffirm the importance of cotrimoxazole prophylaxis for HIV-infected children we believe, that with the emergence of new data, especially around the use of antiretroviral prophylaxis during breastfeeding, the time has come to revisit the guidelines for HIV-exposed infants. Our reasoning for this is described here. Fewer HIV-infected infants The original call for cotrimoxazole prophylaxis was made on the assumption that some 20% of infants could be infected during the ante- and intra-partum period and that a further 15% of infants could be infected through breastfeeding. However, if the proportion of infants who are infected is lower, the benefits of mass prophylaxis may not supersede the risks. Even with interventions for prevention of mother-to-child transmission using single dose nevirapine, Gill et al. in a modelling exercise showed that, as the proportion of HIV-infected infants declined, the benefits of mass prophylaxis on a population level are probably superseded by the risks. (1) Although developing countries still face enormous challenges in increasing coverage of services for prevention of mother-to-child transmission (estimated by UNAIDS to be only 45%), we are now on the brink of a new era with much greater potential for lower proportions of HIV-infected infants. New WHO guidelines call for pregnant women with CD4 count [less than or equal to] 350 to receive highly active antiretroviral therapy (HAART) and those with counts > 350 to receive zidovudine from week 28 with single dose nevirapine during labour. …