This study is being conducted to determine if the uptake of anti-HIV medications called Genvoya® and darunavir is different at several body sites, including mucosal tissues.

Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of MSM acquire HIV after exposure to the rectal mucosa through unprotected receptive anal intercourse. Post-exposure-prophylaxis (PEP) is an intervention that is used to prevent HIV infection soon (72 hours) after a potential exposure. HIV-negative people with a possible exposure to HIV are instructed to take 28 days of a combination anti-HIV medication regimen, Truvada® + Raltegravir. This study is being conducted to determine if the uptake of other anti-HIV medications called Genvoya® and darunavir is different at several body sites, including mucosal tissues. These other medications might be considered for PEP regimens in the future.

Inclusion Criteria:

1. HIV-negative man who reports receptive anal sex with another man in the last 6 months
2. Aged 18-49 years
3. Not currently taking PrEP and no plans to initiate during study
4. Not currently taking PEP
5. Able to provide informed consent in English
6. No plans for relocation in the next 3 months
7. Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling
8. Willing to use study products as directed
9. Willing to abstain from receptive anal intercourse 3 days prior to starting study product and for the duration of the study and for 7 days after any rectal biopsy procedure.

Exclusion Criteria:

1. History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal 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

2. Significant laboratory abnormalities at baseline visit, including but not limited to:

   1. Hgb ≤ 10 g/dL
   2. PTT > 1.5x ULN or INR > 1.5x ULN
   3. Platelet count <100,000
   4. Creatinine clearance <60

3. Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:

   1. Uncontrolled or severe cardiac arrhythmia
   2. Recent major abdominal, cardiothoracic, or neurological surgery
   3. History of uncontrolled bleeding diathesis
   4. History of colonic, rectal, or vaginal perforation, fistula, or malignancy
   5. History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa, or untreated sexually transmitted disease with mucosal involvement

4. Continued need for, or use during the 14 days prior to enrollment, of the following medications:

   1. Aspirin or more than 4 doses of NSAIDs
   2. Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
   3. Any form of rectally administered agent besides lubricants or douching used for sexual intercourse

5. Continued need for, or use during the 90 days prior to enrollment, of the following medications:

   1. Systemic immunomodulatory agents
   2. Supraphysiologic doses of steroids
   3. Experimental medications, vaccines, or biologicals

6. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures

7. Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)

8. Current use of hormonal therapy

9. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.

Male