Toledo, Gabriela; (2023) Health risks and outcomes of children who are HIV-exposed and uninfected in the context of maternal lifelong antiretroviral therapy in Malawi. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Widespread availability of antiretroviral therapy (ART) for pregnant and breastfeeding women with HIV has reduced vertical transmission worldwide, while simultaneously leading to a growing population of children HIV-exposed and uninfected (CHEU), currently estimated at 15.9 million. These children are not only exposed to HIV in utero and via breastmilk but also antiretrovirals during a developmentally critical period. Mounting evidence suggests CHEU experience more infectious morbidity, stunting, and developmental impairments than children HIV-unexposed. This thesis aimed to investigate the health risks and outcomes of CHEU up to age 24 months in the context of maternal lifelong ART using data from the National Evaluation of Malawi’s Prevention of Mother-to-Child HIV Transmission Programme, a nationally representative prospective cohort of 3,462 infants HIV-exposed and mothers (2014-2018). Data were collected at three time points and this thesis focuses on birth, growth, morbidity, and developmental attainment of children HIV-free. Findings demonstrated that CHEU are susceptible to poor health in the first two years of life, beginning from birth, marked by preterm and low birthweight, and postnatally as linear growth faltering and infectious morbidity. At 24 months (n=517), 40.4% of children were stunted and 63.8% (n=559) had ever experienced ≥1 diarrhoeal episodes. Health trajectories suggested that greatest risk was experienced around 12 months, and risk analyses pointed towards low birthweight and sub-optimal feeding as the most persistent determinants of poor outcomes over follow-up. Findings were policy-relevant, highlighting areas that could be strengthened in Malawi’s national program such as antenatal care and nutritional monitoring, and support guidelines for CHEU follow-up care. Methodological insights included the challenges of conducting prospective cohorts within clinical settings to monitor long-term child outcomes. Together, these findings demonstrate the vulnerabilities of CHEU during the first two years of life; optimizing their health will be accomplished by widening our focus and strengthening long-term monitoring.

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