OBJECTIVES: We aimed to examine associations between pre-exposure prophylaxis (PrEP) adherence trajectories and HIV acquisition risk and sexually transmitted infection (STI) rate.

METHODS: This retrospective cohort study included new PrEP users among commercially insured enrollees using 2012 to 2021 MarketScan data. We included individuals who used tenofovir-disoproxil-fumarate with emtricitabine or tenofovir-alafenamide with emtricitabine for PrEP. Using group-based trajectory modeling we identified distinct trajectories of PrEP adherence. Primary outcome was incidence of HIV acquisition. Secondary outcome was STI rate. Outomes were compared among identified trajectory groups. We used inverse probability treatment weighting time-varying Cox proportional hazards models for HIV outcome and Poisson regression models to compare STI risks among identified trajectory groups.

RESULTS: Among 23,258 new PrEP users identified, 96% were male, and 33% were 25-34 years of age. We identified 4 distinct adherence patterns (Figure) in the cohort: nonadherent (10.5%), rapidly declining (25.4%), gradually declining (24.3%), and consistently high (39.8%) adherence groups. Compared with the nonadherent group, groups with gradually declining adherence (adjusted hazard ratio (aHR): 0.53 [0.31–0.90]) and consistently high adherence (aHR: 0.50 [0.30–0.84]) showed decreased HIV incidence risks. Compared with the nonadherent group, groups with rapidly declining adherence (adjusted incidence rate ratio (aIRR): 1.35 [1.07–1.72]), gradually declining adherence (aIRR: 1.73 [1.38–2.18]) and consistently high adherence (aIRR: 2.06 [1.64–2.58]) showed increased STI risks.

CONCLUSIONS: Our findings support benefit of continuing and remaining adherent to PrEP, as gradually declining and consistently high adherence to PrEP was associated with a lower risk of HIV. However, these groups were associated with an increased risk of STI. Findings from this study can inform public health strategies, clinical guidelines, and interventions aimed at maximizing PrEP effectiveness in reducing new HIV infections while developing targeted strategies to prevent STI infections among PrEP use.