The Doxy-PEP Impact Study: a multi-city US longitudinal cohort to evaluate doxy-PEP field effectiveness, investigate associated antimicrobial resistance, and establish doxy-PEP to need ratios - Sexually transmitted infections (STIs) continue to rise in the US and globally, disproportionately affecting men who have sex with men (MSM) and transgender women (TW), with the highest rates in people of color, living with HIV (PLWH) and those ≤30 years of age. Doxycycline taken within 72 hours after condomless sex as post- exposure prophylaxis (doxy-PEP) is highly effective and significantly reduces incident STIs in MSM/TW who are at elevated risk of recurrent STIs. Randomized trials demonstrated doxy-PEP reduced chlamydia (CT) and syphilis by >80% and gonorrhea (GC) by >50%, was safe, well-tolerated, and highly acceptable. Doxy-PEP is an important public health tool with potential to help turn the tide on the US's persistent STI epidemic. In October 2023, the CDC gave a Grade A1 recommendation for doxy-PEP for MSM/TW with recent STIs. However, to be effective, doxy-PEP uptake, adherence, and persistence need to be high among MSM/TW at elevated risk for recurrent STIs which includes MSM/TW who already experience significant health disparities, based on age (under age 30) race/ethnicity (Black and Latinx), living with HIV or are taking HIV PrEP. The roll-out of HIV PrEP in the US is an important reminder of the necessity to ensure equitable access to populations with highest need. In parallel with enthusiasm for the public health potential of doxy-PEP, important concerns remain about longer- term doxy-PEP use and potential antimicrobial resistance (AMR) in GC and clinically important “bystander” bacteria, such as Staph aureus and Strep pneumoniae. To address these questions, we propose an open cohort of MSM and TW currently taking doxy-PEP or initiating doxy-PEP per local or national guidelines in sexual health and HIV clinics in five geographically and demographically diverse cities (Atlanta, Detroit, Miami, San Francisco and Seattle). Our Specific Aims are to: 1) Evaluate guideline-based doxy-PEP effectiveness and patterns of use in 2500 MSM and TG by key characteristics, including race/ethnicity, age, gender identity and HIV serostatus as follows: SubAim 1a: Compare doxy-PEP effectiveness and patterns of use in doxy-PEP users to a threshold consistent with at least 50% reduction in early syphilis, chlamydia and gonorrhea from the DoxyPEP Study. SubAim 1b: Use mixed methods, including qualitative methods, to understand users' decision-making about doxy-PEP use with different partners and continuation of doxy-PEP over time. SubAim 1c: Establish a doxy-PEP to need ratio to assess gaps in doxy-PEP uptake and use, and to guide efforts to increase equitable access. 2) Assess the impact of doxy-PEP on antimicrobial resistance in gonorrhea and clinically relevant bystander bacteria.
