Effects of doxycycline post-exposure prophylaxis on bacterial sexually transmitted infections and antiretroviral therapy adherence among adolescents and young adults living with HIV

BACKGROUND: Doxycycline post-exposure prophylaxis (Doxy PEP) has arisen as a potential strategy to reduce bacterial sexually transmitted infections (STIs), including chlamydia, gonorrhea, and syphilis. However, evidence of Doxy PEP's effectiveness in adolescents and young adults remains limited, despite their disproportionate burden of STI diagnoses. This exploratory, real-world study evaluated the impact of Doxy PEP on STI outcomes and antiretroviral therapy adherence within an outpatient pharmacy program within an outpatient clinic serving youth living with HIV. METHODS: We conducted a retrospective pre-post cohort study of patients aged 15-22 years who received Doxy PEP from March 2024 to March 2025. STI testing results for chlamydia, gonorrhea, and syphilis were collected for the year before and after Doxy PEP initiation. Syphilis classifications included no infection, pre-Doxy PEP period infection only, persistent infection, or new post-Doxy PEP period infection. ART adherence was assessed using pharmacy claims-derived proportion of days covered (PDC). Pre- and post-comparisons were performed using paired t-tests and McNemar's exact test. RESULTS: Among 27 eligible patients, chlamydia positivity increased in 8 patients (30%) and decreased in 8 patients (30%) after Doxy PEP initiation (p = 1.00). Gonorrhea positivity increased in 9 patients (33%) and decreased in 7 patients (26%) (p = 0.804). A review of syphilis data showed 14 patients (52%) with no infection, 7 (26%) with pre-Doxy PEP only infection, 4 (15%) with persistent infection, and 2 (7%) with new post-Doxy PEP period infection; p = 0.18. ART adherence remained high and stable (mean PDC 88.5% pre vs. 91.6% post; p = 0.77). CONCLUSIONS: Doxy PEP was not associated with significant reductions in STI positivity in this adolescent and young adult cohort. Although non-significant, directional patterns were observed in syphilis outcomes; these outcomes should be interpreted with caution, given the small sample size. ART adherence remained unaffected, supporting the feasibility of incorporating Doxy PEP into youth HIV programs. Larger studies are needed to clarify Doxy PEP's effectiveness among adolescents and young adults.