Got Doxy- 'Flipping the Script' on STI PEP

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