A Randomized Controlled Trial of Doxycycline Post Exposure Prophylaxis to Prevent Incident Bacterial STIs Among Women in the United States

A Randomized Controlled Trial of Doxycycline Post Exposure Prophylaxis to Prevent Incident Bacterial STIs Among Women in the United States

The bacterial sexually transmitted infections (STIs) chlamydia, gonorrhea, and syphilis cause multiple adverse outcomes in women, and prevention strategies are critically needed. This project will determine the efficacy of doxycycline post-exposure prophylaxis (doxy PEP) to prevent STIs among women through a phase IV, open-label, randomized controlled trial.

The bacterial sexually transmitted infections (STIs) chlamydia (CT), gonorrhea, and syphilis cause multiple adverse outcomes in women, and rates of these infections have increased dramatically over the past two decades. Prevention of these infections is now possible with the use of doxycycline post-exposure prophylaxis (doxy PEP), which has demonstrated efficacy in multiple studies conducted among men from high prevalence groups. However, only one trial of the use of doxy PEP (dPEP Kenya) has been conducted among women, and unfortunately this study had a null result. Our proposed project seeks to evaluate doxy PEP efficacy among women in the United States through an open-label, randomized controlled trial (RCT) conducted in three jurisdictions (New Orleans, LA; Birmingham, AL; Chicago, IL) with high STI prevalence. Close adherence monitoring is critical given that the dPEP Kenya study's null result was likely related to poor medication adherence; thus, this trial will monitor and reinforce doxycycline adherence throughout the study using a novel PCheck app developed by our team, test urines for doxycycline levels on all participants, and hair on a nested cohort. The study's aim to conduct an RCT in 519 sexually active, non-pregnant women aged 18-35, randomizing 2:1 to better evaluate adverse events related to doxy PEP, powering the study on CT as the most commonly anticipated STI; sensitivity analyses will compare CT rates based on adherence measured by doxycycline levels in urine and by self-reported pill-taking. To execute these aims, we have assembled a multidisciplinary team with extensive expertise in the conduct of clinical trials, bioinformatics, biostatistics, infectious diseases epidemiology, STI prevention, the vaginal microbiome, behavioral health interventions, and qualitative science. MPIs Clement, Kissinger, and Muzny collectively have decades of collaborative experience enrolling priority populations in large clinical trials aimed to improve sexual health outcomes. Ultimately, this trial has the potential to have substantial public health impact, leading to a novel bacterial STI prevention intervention to reduce the undue burden of incident bacterial STIs among women.

Inclusion Criteria:

• Female

• Aged 18-35

• Reporting condomless vaginal sex with men AND least one of the following:

  1. diagnosis of CT, gonorrhea, syphilis, or trichomonas in the past year
  2. reporting 2 or more sexual partners in the past 6 months

• Plan to continue to be sexually active over the next year

• Have smartphone and be willing to engage with an app

• If HIV+: Viral load<200 copies/ml and CD4 count >200 cells/mm3

Exclusion Criteria:

• Pregnant, nursing, or intending to become pregnant
• Reported allergy to tetracyclines
• Liver disease or end-stage renal disease
• Non-English Speaking
• Taking concomitant medications which may impact doxycycline metabolism (e.g., systemic retinoids, antacids, barbiturates, carbamazepine, phenytoin, iron, warfarin, rifampin)
• Not willing to take doxy PEP or comply with study procedures
• Unable to provide informed consent