Trajectories of Adherence to Oral Pre-exposure Prophylaxis and Risks of HIV and Sexually Transmitted Infections.

Background: Pre-exposure prophylaxis (PrEP) effectiveness is highly dependent on medication adherence, which is associated with differential HIV risks and possibly sexually transmitted infection (STI). Methods: This retrospective cohort study of PrEP users (01/01/2012-12/31/2021) used the MarketScan database of commercially insured enrollees to examine PrEP adherence trajectory groups' associations with HIV and STI acquisition risks. Distinct PrEP adherence trajectories were identified by group-based trajectory modeling among individuals who used oral PrEP. The primary outcome was HIV acquisition incidence, and secondary was STI rate, compared among trajectory groups. Inverse probability treatment weighting time-varying Cox proportional hazards models assessed HIV acquisition, and Poisson regression models assessed STI. Results: Among 23 258 oral PrEP users, 4 distinct PrEP adherence patterns were identified: minimal use (10.5% of the cohort), rapidly declining (25.4%), gradually declining (24.3%), and consistently high (39.8%). Compared with the minimal use group, the gradually declining (adjusted hazard ratio [AHR], 0.53; 95% CI, 0.31-0.90) and consistently high (AHR, 0.50; 95% CI, 0.30-0.84) PrEP adherence groups showed decreased HIV incidence risks. Compared with the minimal use group, the rapidly declining (adjusted incidence rate ratio [AIRR], 1.35; 95% CI, 1.07-1.72), gradually declining (AIRR, 1.73; 95% CI, 1.38-2.18), and consistently high (AIRR, 2.06; 95% CI, 1.64-2.58) groups were associated with increased STI risk. Conclusions: These findings underscore the benefits of continuing and remaining adherent to PrEP and may also inform public health strategies, clinical guidelines, and interventions aimed at maximizing the effectiveness of PrEP in reducing new HIV infections while developing targeted strategies to prevent STIs with PrEP use.