PROJECT SUMMARY: TB contributes to substantial comorbidity among children with HIV infection or HIV exposure. Over one-third of pediatric TB deaths in Africa were associated with HIV in 2018. TB-HIV co-treatment is vital to decrease mortality. However, this co-treatment imposes serious management challenges, including high pill burden, drug toxicity, drug-drug interaction, immune reconstitution inflammatory syndrome (IRIS), and potential consequences on childhood growth, which is not well-characterized. The parent grant aimed to determine the impact of HIV exposure and infection on anti-mycobacterial innate immune responses. This proposed Diversity Supplement aims to determine the effects of TB treatment and prevention therapy on health outcomes and growth responses in HIV infected and exposed children. The first aim of the proposed Diversity Supplement is to determine the effects of TB co-treatment on virologic, immunologic, and growth response among children living with HIV (CLHIV) newly initiating ART, for which we will use available data from the completed Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART) (PUSH) (NCT02063880), a randomized trial among CLHIV. HIV exposed uninfected (HEU) children are at increased risk of Mtb infection and disease, and we recently completed a clinical trial [Infant TB Infection Prevention Study (iTIPS) (NCT02613169)] to determine whether isoniazid prophylaxis (IPT) decreases Mtb infection. The effect of IPT on the growth of children is not well characterized. In the second aim of the proposed Diversity Supplement, we will determine the effect of IPT on infant growth among HEU using data from the iTIPS trial. Research findings will inform strategies to optimize TB-HIV co- treatment in CLHIV and will provide additional evidence regarding IPT safety in infancy.

PROJECT NARRATIVE: Tuberculosis (TB) causes substantial morbidity and mortality to CLHIV, and TB-HIV co-treatment poses serious management and health challenges. IPT is an effective intervention for preventing TB disease in children; however, its' effect on infant growth is not well characterized. This study aims to determine the effects of TB co- treatment on virologic, immunologic, and growth response among CLHIV newly initiating ART and the impact of IPT on infant growth among HEU to inform strategies to optimize TB-HIV co-treatment and provide additional evidence regarding IPT safety in infancy.