Tsepamo Next Generation: Optimizing HIV Treatment and Prevention Strategies for Pregnant Women in Botswana

/Abstract This study will address two critical questions related to pregnant women living with HIV and their infants: 1) can two-drug antiretroviral treatment (ART) be used safely and effectively among pregnant women living with HIV? and 2) how can we most efficiently identify those at risk and prevent HIV infection among pregnant women? For Aim 1, there is a need to research two-drug ART with dolutegravir/lamivudine (DTG/3TC) in pregnancy, particularly in resource-limited settings. Botswana's imminent transition to DTG/3TC for all adults presents a unique opportunity to study its effects on maternal weight gain, viral suppression in pregnancy, adverse birth outcomes, and vertical transmission. This aim can be efficiently accomplished within the existing Tsepamo Study surveillance system by creating an emulated clinical trial and by utilizing over 2,400 mother–child pairs with targeted specimen collection. For Aim 2, the Tsepamo surveillance infrastructure also provides an ideal mechanism to identify recently infected pregnant women. We will determine the drivers of incident HIV infections in this population by 1) performing phylogenetic analyses linked to nationwide cluster surveillance performed at the Botswana Harvard Health Partnership (BHP), including evaluation of transmitted drug resistance, and 2) using in-depth interviews and questionnaires to understand current demographic and behavioral risk factors. Additionally, we will assess whether recent seroconverters would have been good candidates for / accepting of long-acting PrEP. Ultimately, the findings of this study will inform international guidelines, ensuring safer ART options for pregnant women that harmonize with adult treatment guidelines and inform upcoming strategies to roll out long-acting PrEP in high-risk women. Project Number: 1R01HD120132-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Roger Shapiro (+1 co-PI) | Institution: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH, BOSTON, MA | Award Amount: $497,029 | Activity Code: R01 | Study Section: HIV Comorbidities and Clinical Studies Study Section[HCCS] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HD12013201