BACKGROUND: Despite high oral pre-exposure prophylaxis (PrEP) uptake among young heterosexual cisgender women, early discontinuation is frequent. It is unclear whether this aligns with potential HIV exposure. METHODS: Young women aged 16-25 years and ≥1 of their male partners were enrolled in separate but linked longitudinal HIV PrEP studies in Kampala, Uganda, from 2018 to 2021. Data on sexual behavior, PrEP use, sexually transmitted disease positivity, and Y chromosome DNA (Yc DNA
a marker for condomless sex) were collected at enrollment and quarterly visits. Potential HIV exposure was defined as one of the following in the past 3 months: any sexually transmitted disease, detection of Yc DNA, condomless vaginal sex, or multiple sex partners. Alignment between potential HIV exposure and PrEP use by participants was examined using generalized estimating equation (GEE) regression. RESULTS: Eighty-eight young women (median age = 20.6 years, interquartile range 19.5-22.0) and 124 male partners (median age = 23.5 years, interquartile range 21.0-26.0) were included. Women and men were dispensed PrEP in 66.9% and 60.5% of their first linked visits, respectively. PrEP dispensation was more common when women or men self-reported condomless vaginal sex and multiple sex partners or when women had Yc DNA detected in vaginal swabs. Men's self-report of multiple partners (adjusted prevalence ratio = 1.56, P = 0.012) and the detection of Yc DNA (adjusted prevalence ratio = 1.52, P = 0.040) were significantly associated with women's PrEP dispensation. CONCLUSIONS: Women and their male partners may align their PrEP use with their HIV risk behaviors, providing some reassurance that PrEP discontinuation in young people often aligns with sexual behavior. Greater attention to measurement of and mismatches in PrEP discontinuation and potential HIV exposure is needed.