Impact of Dolutegravir on Viral Suppression, Retention, and Risk of Non-Communicable Diseases among Persons Living with HIV in South Africa. - Project Summary South Africa has the world’s largest burden of HIV, with almost eight million people living with HIV and the largest HIV treatment program in the world. With the ongoing development of new and more effective antiretroviral therapies (ART), it is important to understand the effect of different treatment strategies on treatment and care outcomes as well as the risk of other co-morbidities. Prior research by the applicant and sponsors evaluated South Africa’s policy change in 2019 of initiating HIV treatment with a regimen containing dolutegravir rather than efavirenz. This work demonstrated that retention and viral suppression outcomes are similar before and after the policy change. However, this research utilized a regression discontinuity design, so the analysis was limited to those who initiated within 3-months on either side of the date of the policy change and further work is needed to see if this result holds once there is more experience with the new medication. In addition, extensive access to ART in South Africa has led to people living with HIV longer. There is growing concern that persons living with HIV, in particular those on a dolutegravir-based ART regimen, may be at increased risk of non-communicable diseases (NCDs). However, the severity of this risk is unclear. The aim of this proposal is to better characterize the effect of different HIV treatment strategies on retention and viral suppression, and to address the gap in literature on the risk of dolutegravir on NCDs. Aim 1 leverages the Target Trial Framework to assess the effect of dolutegravir treatment over 12- and 24-months on retention and viral suppression in comparison to efavirenz over the same time period. Aim 2 will utilize sequential randomized trials and a Target Trial Framework approach to assess, among patients initiating a treatment regimen containing efavirenz, the effect on retention and viral suppression after switching to dolutegravir within the first 12-months of treatment compared to remaining on efavirenz. Aims 1 and 2 will use data from a large, prospective cohort of patients receiving care at a public health-sector clinic in South Africa. Aim 3 will assess the effect of dolutegravir treatment on the risk of weight gain, hypertension, and type 2 diabetes mellitus in comparison to efavirenz. Aim 3 will utilize data from clinics located in South Africa’s KwaZulu-Natal, Northern Cape, Limpopo, Mpumalanga, and Gauteng provinces. A detailed training plan, in conjunction with these research aims, will provide the applicant with hands-on training to support her development as an independent infectious disease epidemiologist with expertise in NCDs and novel epidemiologic methods for observational data. The training plan outlines mentorship opportunities provided by sponsors, who are experts in their field and have a well-established record of collaboration and mentorship.
