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Project Topic
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Background: Sub-Saharan Africa (SSA) alone has at least nine out of every 10 children living with HIV globally and monitoring in this setting remains suboptimal, even as these children grow older. With scalability of antiretroviral therapy (ART), several HIV-infected children are growing towards adolescence (over 2.1 million) in resource-limited settings, with the potentials to reach adulthood. However, despite an overall reduction in HIVrelated mortality, there are increasing deaths among adolescents living with HIV (ALHIV), with limited evidence for improved policy-making. Of note, strategies for adolescent transition from pediatrics to adult-healthcare are critical to ensure successful treatment response, longer life expectancy and their contribution to development in SSA. Interestingly, with uptakes in prevention of mother-to-child transmission (PMTCT), HIV testing and universal antiretroviral therapy (ART) for infected-children, wide-use of low genetic-barrier drugs, frequent drug stock-outs, poor-adherence, and high viremia among children in SSA, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance (HIVDR) emergence, especially after years of paediatric ART exposure. Therefore, monitoring ART response in adolescents and evaluating HIVDR patterns might limit disease progression and guide on subsequent active treatment options for SSA ALHIV. Objectives: Among Cameroonian ALHIV receiving ART, we shall monitor response to first- and second-line regimens, drug resistance profiling and HIV-1 variability during one-year follow-up. Specifically, we shall evaluate the rate of immunovirologic failure at enrolment, month-6 and month-12; acquired HIVDR-associated mutations; HIV-1 subtype distribution; genetic variability in circulating (plasma) versus archived (cellular) viral strains; and HIVDR early warning indicators (EWIs). Methods: An observational, prospective and open cohort-study conducted among 250 ALHIV (10-19 years old) receiving ART in the centre region of Cameroon, and followed-up until 12 months. Following consecutive sampling at enrolment, plasma viral load and CD4/CD8 count will be measured, and genotypic resistance testing (GRT) will be performed both in plasma and in buffy coat for participants experiencing virological failure (two consecutive viremia >=1000 copies/ml). Plasma viral load and CD4/CD8 will be monitored for all participants at 6 and 12 months after enrolment. HIVDR-EWIs will be monitored and survival analysis performed during the 12 months follow-up. Primary outcomes are rates of virological failure, acquired HIVDR, and mortality. Overall impact: Our findings will provide evidence-based recommendations to ensure successful transition from paediatrics to adult ART regimens and highlight further needs of active ART combinations, for reduced morbidity and mortality in populations of ALHIV within SSA.
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