Female sex workers (FSW) and adolescent girls and young women (AGYW) face a disproportionately high risk of HIV in South Africa. Oral preexposure prophylaxis (PrEP) can avert new infections, but its effectiveness is linked to consistent use. Early discontinuation of PrEP in this population is high, but less is known about longitudinal patterns of PrEP use, including patterns of re-initiation and cycling.

Longitudinal descriptive analysis of routine program data.

Between 2016 and 2021, 40 681 FSW and AGYW initiated PrEP at TB HIV Care, the largest PrEP provider to this population in South Africa and were included. Using survival analyses and group-based trajectory modeling, we described patterns of initiation, discontinuation, re-initiation, and cycling.

Total initiations increased over the life of the program for both FSW and AGYW. About 40% of FSW [0.41, 95% confidence interval (CI) [0.40–0.42]] and AGYW (0.38, 95% CI [0.37–0.38]) remained on PrEP at one month. FSW were more likely to restart PrEP, however <10% restarted PrEP within a year of initiation. Three latent trajectory groups of PrEP use were identified for FSW (low use, early cycling, and ongoing cycling) and two for AGYW (low use and ongoing cycling). Persistence was negatively associated with initiation among AGYW, but there was no clear relationship among FSW. Those initiating later in the program and older women had a reduced risk of discontinuation.

Persistence on PrEP was low, but cycling on and off PrEP was common, with early missed visits and inconsistent, but ongoing use. A push to increase PrEP initiations needs to factor in readiness and persistence support, to achieve public health impact.