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

University Of California, San Francisco, San Francisco CA

Investigators

Abstract

Sexually transmitted infections (STIs) continue to rise in the US and globally, disproportionately affecting men with male partners, with the highest rates those with a previous STI, 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 men with male partners 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 to consider doxy-PEP for men with male partners with recent STIs. However, to be effective, doxy-PEP uptake, adherence, and persistence need to be high among persons at elevated risk for recurrent STIs, including under age 30, Black and Hispanic populations, those living with HIV or are taking HIV PrEP, and potentially women at risk of STIs who choose to take doxy-PEP. The roll-out of HIV PrEP in the US is an important reminder of the necessity to ensure access to populations with highest need to realize the public health potential of a biomedical intervention. In parallel with enthusiasm the potential of doxy-PEP to reduce bacterial STIs, 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 men and women 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). Aim 1: Evaluate effectiveness of doxy-PEP and patterns of use in 2500 men and women in five US cities by key characteristics, including age, STI history, sexual partners, and HIV serostatus. SubAim 1a: Compare doxy-PEP effectiveness and patterns of use in an open cohort of doxy-PEP users to a threshold consistent with at least 50% reduction in early syphilis, CT, and GC from the DoxyPEP RCT. SubAim 1b: Use mixed methods to understand users’ decision-making about doxy-PEP use with different partners and continuation of doxy-PEP. SubAim 1c: Establish a doxy-PEP to need (DPtN) ratio to assess gaps in doxy-PEP access and use and to guide efforts to increase effective use. 2) Assess the impact of doxy- PEP on antimicrobial resistance in gonorrhea and clinically relevant bystander bacteria.