Flipping the script on STI prevention with doxycycline post-exposure (Doxy-PEP).

The Effects of Doxycycline on Inflammation and the Microbiome: 'Flipping the Script' on STI PEP

Phase 4 Interventional Emory University · NCT07215325

We will test whether taking doxycycline after sex (Doxy-PEP) changes inflammation and the body's bacteria in adults assigned male at birth who have HIV or are using HIV PrEP.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years and up
SexMale
SponsorEmory University Academic / other
Locations2 sites (Atlanta, Georgia and 1 other locations)
Trial IDNCT07215325 on ClinicalTrials.gov

What this trial studies

This Phase 4 interventional study gives doxycycline monohydrate 200 mg as post-exposure prophylaxis to adults assigned male at birth, including people living with HIV on suppressive ART and people without HIV who are on PrEP. Participants attend five in-person visits over about 12 weeks, including blood draws and two rectal tissue biopsy visits to measure systemic and gut inflammation and microbiome/resistome changes. The study compares biological samples before and after Doxy-PEP use and includes specimen banking for future research. Safety monitoring and observational comparisons are included to detect adverse effects and potential antibiotic resistance signals.

Who should consider this trial

Good fit: Adults over 18 assigned male at birth who are either living with HIV on stable suppressive ART (viral load <50 copies/mL and CD4 >300 cells/µL) or HIV-negative people on stable PrEP and willing to undergo blood draws and rectal biopsies are ideal candidates.

Not a fit: People with uncontrolled comorbidities, a history of inflammatory bowel disease, those not assigned male at birth, those not meeting ART/PrEP stability requirements, or anyone unwilling to undergo rectal biopsies are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this could show whether Doxy-PEP reduces systemic or gut inflammation or causes microbiome changes that help guide safer STI prevention strategies.

How similar studies have performed: Previous Doxy-PEP trials have shown reductions in bacterial STIs in high-risk populations, but the systemic and gut anti-inflammatory and microbiome effects are less well studied.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Age \>18 years
* Assigned male sex at birth
* Good general health as assessed by a clinician at the screening study visit
* For people with HIV, on suppressive antiretroviral therapy for at least 6 months with the most recent viral load documented \<50 copies/ml and the most recent cluster of differentiation 4 (CD4)\>300cells/ul
* For people without HIV, taking oral daily, oral on-demand, or injectable pre-exposure prophylaxis for at least 3 months at the time of enrollment, with plans to continue for the duration of the study
* Additional criteria apply

Exclusion Criteria:

* Severe/uncontrolled comorbidities that could influence immune outcomes (e.g., diabetes, hypertension, co-infections), as assessed by the investigator.
* History of inflammatory bowel disease (IBD) or other inflammatory, infiltrative, infectious, or vascular condition involving the lower GI tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel.
* Known allergy to doxycycline
* Use of any antibiotics within 3 months before screening
* Significant lab abnormalities at baseline visit for rectal biopsies,
* Continued need for the following medications during the study:

  1. Aspirin
  2. Warfarin, heparin (LMW or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
  3. Any form of rectally administered agent besides products (lubricants or douching) used for sexual intercourse
  4. NSAIDS within 72 hours of rectal sampling procedures
* Continued need for, or use during the 90 days before enrollment, of the following medications:

  1. Systemic immunomodulatory agents
  2. Supraphysiologic doses of corticosteroids, except for short-course corticosteroids \<7 days duration at the discretion of the investigator. (Gender affirming hormone therapy is not exclusionary.)
  3. Use of experimental medications, vaccines, or biologicals in the 12 months before enrollment

Where this trial is running

Atlanta, Georgia and 1 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Sexually Transmitted InfectionsDoxycycline post-exposure prophylaxisGut inflammationPreventionPEPSTI
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.