PrEP Discontinuation Among Sex Workers: Gender Disparities and the Impact of Housing Instability in a Prospective Cohort Study

Abstract Background PrEP discontinuation remains a major challenge in HIV prevention, yet comparative data on retention among sex workers—particularly across gender identities—are scarce. We evaluated the incidence of PrEP discontinuation and associated risk factors in a diverse cohort of sex workers in Madrid, Spain. Methods We conducted a prospective observational study of HIV-negative adults engaged in sex work initiating PrEP at a specialized hospital-based clinic between November 2022 and March 2025. We evaluated the incidence of PrEP discontinuation and associated structural and demographic factors in a prospective cohort of sex workers in Madrid, Spain. Predictors were assessed using Kaplan–Meier and Cox models. Results Among 189 participants (30.2% cisgender women, 33.9% cisgender men, 36.0% transgender women), the overall discontinuation incidence was 9.9 per 100 person-months, with a median retention time of 7.0 months. Loss to follow-up was the primary cause (76.3%). Marked gender disparities were observed, with cisgender women exhibited the highest discontinuation rate (20.8 per 100 person-months) and shortest retention (median 3.8 months). In multivariable analysis, cisgender men (adjusted hazard ratio [aHR], 0.37; 95% CI, 0.21–0.62) and transgender women (aHR, 0.30; 95% CI, 0.18–0.50) had a significantly lower risk of discontinuation compared with cisgender women. Housing instability was independently associated with increased discontinuation risk (aHR, 1.91; 95% CI, 1.17–3.12). Conclusions PrEP discontinuation is highly prevalent among sex workers, disproportionately affecting cisgender women and those experiencing housing instability. Hospital-based delivery models may be insufficient to sustain engagement among structurally vulnerable populations. Tailored, equity-focused strategies addressing structural barriers are urgently needed to sustain engagement.