Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities

Men who have sex with men (MSM) and Transgender women (TGW) who have sex with men continue to
be disproportionately affected by HIV. Over 60% of new HIV infections in the US occur among
MSM. The majority of HIV infections among MSM and TGW occur through exposure to the rectal
mucosa during receptive anal intercourse (RAI). Pre-exposure prophylaxis (PrEP) is a new HIV
prevention method that is recommended by CDC and WHO for MSM at risk of HIV infection. PrEP
entails taking an anti-HIV medication (Truvada®; tenofovir/emtricitabine) on a daily basis to
prevent HIV infection. However, current tenofovir- based regimens have shown to have side
effects that researchers are hoping to reduce in newly developed anti-HIV agents. This study
is designed to examine the ability of these new agents to penetrate mucosal tissues and
potentially prevent HIV infection during RAI exposure for MSM and TGW.

Inclusion Criteria:

- HIV-negative man who reports receptive anal sex with another man in the last 6 months

- Male to female transgender women who have sex with men who report receptive anal
intercourse with another man in the last 6 months and are not currently taking
hormonal therapy or plan to take hormonal therapy for the duration of the study

- Not currently taking PrEP and no plans to initiate during study

- Able to provide informed consent in English

- No plans for relocation in the next 3 months

- Willing to undergo peripheral blood and rectal biopsy sampling

- Willing to use study products as directed

- 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:

- 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

- 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

- 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 or vaginal mucosa, or untreated sexually
transmitted disease with mucosal involvement

- 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 products lubricants or douching
used for sexual intercourse

- 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

- Intent to use HIV antiretroviral pre-exposure prophylaxis (PrEP) during the study,
outside of the study procedures

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

- Current use of hormonal therapy

- 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.