Mentored Scientist Award

Weight gain and metabolic consequences of switch to dolutegravir in Western Kenya

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Dolutegravir was recently recommended as a component of first-line antiretroviral therapy (ART) for all adults living with HIV by the World Health Organization due to improved efficacy and tolerability over prior regimens. However, recent studies, including two randomized trials in sub-Saharan Africa, have shown significant weight gain associated with dolutegravir among ART-naïve patients newly initiating dolutegravir. It is not known whether switch to dolutegravir among ART-experienced patients will result in similar weight gain. Furthermore, there are case-reports of other metabolic complications following initiation of dolutegravir, including new-onset diabetes, however the incidence of these complications following switch to dolutegravir in sub-Saharan Africa is currently unknown. To better understand weight changes following switch to dolutegravir, we will undertake a retrospective cohort study of patients who have recently switched to dolutegravir at a large outpatient HIV clinic in rural western Kenya and, using within-participant controls, will evaluate changes in weight gain following switch to dolutegravir. Because metabolic disease monitoring and diagnostic capabilities are limited during routine HIV care in western Kenya, we will also undertake a prospective cohort study of patients switching to dolutegravir to evaluate incident weight changes, diabetes, and metabolic syndrome. This study will provide important and timely insight into the relationship between dolutegravir and incident weight gain and metabolic consequences, informing the current global discussion about the risks and benefits of dolutegravir. This study will also provide important preliminary data on the overall burden of metabolic disease among patients on contemporary dolutegravir-based antiretroviral therapy, providing important context for the setting in which I plan to design and pilot strategies for improving metabolic disease monitoring and treatment for people living with HIV in my planned K23 mentored career development award