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Due to lifelong combination antiretroviral therapy (cART) in persons living with HIV, there has been a decline in mother-to-child transmission of HIV. However, this has led to a growing population of infants that are exposed to HIV but not infected (iHEU). These infants have a higher mortality risk and display altered immunological profile. In addition, iHEUs exhibit impaired growth compared to infants not exposed to HIV (iHU). The mechanisms underlying these phenomena are not well understood. Postnatally, iHEU are also treated with antiretroviral prophylaxis (ARVs) even though they are not HIV infected. In the modern era of universal antiretroviral therapy, it is difficult to distinguish the effects of cARTs exposure and infant ARVs from those of exposure to HIV and/or other maternal infections. Animal models provide an excellent platform to study the effect of antiretrovirals during pregnancy and early life on offspring health. In this project, we will study the effect of maternal cARTs and early life antiretroviral treatment on maternal and offspring gut microbiota (bacteriome and virome). In addition, we will assess the effect of maternal and offspring antiretrovirals on growth (weight, body length) and bone development(bone mineral density, bone mineral content). Finally, we will investigate whether maternal cART or infant antiretrovirals impact systemic or local inflammation. All experiments will be done in mice.
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