The University of KwaZulu-Natal, with support from the Family Larsson-Rosenquist Foundation (FLRF), is testing two hypotheses among HIV-exposed but uninfected (HEU) infants in South Africa:
• Breastfed HEU infants who do not receive co-trimoxazole (CTX) will not have inferior outcomes in terms of incidence of common childhood illnesses or mortality compared to infants who do receive CTX
• Breastfed HEU infants who do receive CTX will experience a disruption in the normal development of the protective layer of the gut compared to infants who do not receive CTX
The study was launched in 2013, and was funded by the HIV Prevention Research Unit of the South African Medical Research Council and a USD 166,000 donation from FLRF. It is based on the current World Health Organization (WHO) recommendation that all HEU infants be given prophylaxis antibiotics until they are weaned, and until HIV infection can be excluded.
“The absence of proven benefits in HEU breastfed infants associated with infectious diseases, coupled with the small number of infants expected to be infected with HIV, and now being identified by healthcare systems, begs reconsideration of the ‘blanket’ approach to antibiotics as prophylaxis for all infants born to HIV-infected mothers.” – Anna Coutsoudis, PhD, Research Professor, Department of Paediatrics & Child Health, University of KwaZulu-Natal
Given the global rise in antibiotic resistances, in part due to antibiotic overuse and inappropriate indication, clinical findings from this study could lead to consequential advancements. Insights gained have the potential to:
• help redefine HIV prevention guidelines for breastfed HEU infants
• support healthcare providers – and families and communities – with the most current evidence-based knowledge available
D’Souza AW, Moodley-Govender E, Berla B, Kelkar T, Wang B, Sun X, et al. Cotrimoxazole prophylaxis increases resistance gene prevalence and α-diversity but decreases β-diversity in the gut microbiome of human immunodeficiency virus-exposed, uninfected infants. Clin Infect Dis. 2020;71(11):2858–68. DOI: 10.1093/cid/ciz1186
Daniels B, Coutsoudis A, Moodley-Govender E, Mulol H, Spooner E, Kiepiela P, et al. Effect of co-trimoxazole prophylaxis on morbidity and mortality of HIV-exposed, HIV-uninfected infants in South Africa: a randomised controlled, non-inferiority trial. Lancet Glob Health. 2019;7(12):e1717–27. DOI: 10.1016/S2214-109X(19)30422-X
Daniels B, Coutsoudis, A, Moodley-Govender E, Mulol H, Spooner E, Kiepiela P et al. Effect of co-trimoxazole prophylaxis on morbidity and mortality of HIV-exposed, HIV-uninfected infants in South Africa: a randomised controlled, non-inferiority trial. Lancet Glob Health. 2019;7(12):PE1717-E1727, DOI: 10.1016/S2214109X(19)30422-X.
Evans C, Prendergast AJ. Co-trimoxazole for HIV-exposed uninfected infants. Lancet Glob Health. 2017;5(5):e468-e469. DOI: 10.1016/S2214-109X(17)30147-X.
Lockman S, Hughes M, Powis K, Ajibola G, Bennett K, Moyo S et al. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial. Lancet Glob Health. 2017;5(5): e491-e500. DOI: 10.1016/S2214-109X(17)30143-2.
Coutsoudis A, Daniels B, Moodley-Govender E, Ngomane N, Zako L, Spooner E et al. Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol. BMJ Open. 2016;6(7):e010656. DOI: 10.1136/bmjopen-2015-010656.
Coutsoudis A, Coovadia HM, Kindra G. Time for new recommendations on cotrimoxazole prophylaxis for HIV-exposed infants in developing countries? Bull World Health Organ. 2010;88(12):949-950. DOI: 10.2471/BLT.10.076422.
WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach – 2nd ed. 2016. Available here.
WHO. Guidelines on post-exposure prophylaxis for HIV and the use of co-trimoxazole prophylaxis for HIV-related infections among adults, adolescents and children: recommendations for a public health approach: December 2014 supplement to the 2013 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2014. Available here.