Evaluating the biomedical and behavioral drivers of HIV incidence decline in adolescent girls and young women in Uganda: A mathematical modeling study

by Adam Akullian, Victor Ssempijja, Daniel Bridenbecker, Fred Nalugoda, Gertrude Nakigozi, John Santelli, Philip Kreniske, Larry W. Chang, Steven J.

Reynolds, Robert Ssekubugu, Ronald H. Gray, Maria J.

Wawer, Thomas C. Quinn, Ronald M.

Galiwango, William J. M.

Probert, Jeffrey W. Imai-Eaton, Oliver Ratmann, Christophe Fraser, Joseph Kagaayi, Godfrey Kigozi, Mary Kate Grabowski, David Serwadda Background HIV incidence among adolescent girls and young women (AGYW) in eastern and southern Africa has declined substantially over the past two decades.

These declines are often attributed to biomedical HIV prevention strategies, though concurrent changes in sexual behavior may also contribute. We evaluated the contributions of biomedical and behavioral drivers to historical incidence decline in AGYW and projected their impact on incidence trajectories over the next 30 years.

Methods and findings We conducted a mathematical modeling study using data from the Rakai Community Cohort Study (RCCS), an open, population-based cohort of adults aged 15–49 years in 30 communities in Rakai, Uganda. We used an agent-based HIV-1 transmission model calibrated to cohort data to estimate HIV incidence trends among AGYW, aged 15–24, and to quantify the independent and combined effects of antiretroviral therapy (ART), voluntary medical male circumcision (VMMC), and changes in age at first sex (AFS).HIV incidence among women aged 15–24 declined by 71% between 2000 and 2019, from 1.57 to 0.45 per 100 person-years, representing the largest decline across female age groups in the cohort.

Increasing AFS over the study period (by approximately 3 years in women and 2 years in men) was the largest contributor to incidence declines among adolescent women aged 15–19, averting 17% of cumulative infections between 2000 and 2020 and 37% between 2000 and 2050. Among women aged 20–24, ART scale-up had the greatest impact, averting 13% of infections by 2020 and 43% by 2050.

VMMC contributed modestly to historical declines but had larger projected effects over longer time horizons. ART, VMMC, and delays in AFS acted additively to reduce HIV incidence among AGYW.

Study limitations include reliance on self-reported sexual behavior and the use of a mathematical model that cannot capture all real-world sexual network dynamics. Conclusions Both biomedical HIV interventions and broader behavioral changes contributed to declines in HIV incidence among AGYW.

Sustaining continued incidence declines in young women will require maintaining both the protective changes in sexual behaviors and effective biomedical interventions.