Alteration of intestinal microbiota composition and function by co-trimoxazole use and the effect of these changes on growth in HIV-infected children

Malnutrition in early life underlies almost half of all child deaths globally and has long-term negative effects on education and productivity. HIV infection further compounds these effects in sub-Saharan Africa. The World Health Organization (WHO) recommends daily use of the antibiotic co-trimoxazole (CTX) to prevent infections in HIV-infected children. In addition to reducing deaths from infections, CTX also improves growth, possibly by changing the population of "good" microbes in the intestines.

But using antibiotics on a daily basis risks emergence of antibiotic resistant microbes, which could cause disease.

This project will test the hypotheses that daily CTX use in HIV-infected children causes the population of the microbes in their intestines to show:

1. An increase in the number of antibiotic resistance genes
2. An increase in the number of genes that encode proteins involved in nutrient harvesting (e.g. carbohydrate digestion)
3. A decrease in genes involved in virulence
4. That these changes drive the effect of CTX on growth

We will analyze child growth measurements and clinical data and will characterize genetic changes to the microbiota in stool specimens using DNA sequencing methods. Data and samples were collected through ARROW, a randomized trial designed to study the impact of CTX use on a number of health outcomes in HIV-infected children in Zimbabwe.

Our goal is to understand how daily use of CTX impacts child health in a wider context and to inform WHO recommendations on CTX use in HIV-infected children.