PrEP, Lube, and the Rectal Mucosa in MSM at Risk of HIV

Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The
majority of HIV infections among MSM occur through exposure to the rectal mucosa during
receptive anal intercourse (RAI). During RAI, many MSM will use lubricants, which can
potentially cause mucosal inflammation and damage. A new HIV prevention intervention, called
pre-exposure prophylaxis (PrEP), recommends that MSM at risk of HIV infection take a daily
anti-HIV medication called Truvada (tenofovir/emtricitabine) which is highly effective.
However, it is not known if the use of lubricant during RAI will interfere with the efficacy
of PrEP for HIV prevention.

Inclusion Criteria:

- HIV-negative man who reports receptive anal sex with another man in the last 6 months
aged 18-49 years

- Male to female transgender women who are not currently taking hormonal therapy or
plan to take hormonal therapy for the duration of the study

- Not currently taking pre-exposure prophylaxis (PrEP) and no plans to initiate during
study

- Able to provide informed consent in English

- No plans for relocation in the next 6 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 study visit 2
(4-16 weeks after the screening visit)and 10 days prior to study visit 4 (5-26 weeks
after the screening visit)

- Willing to abstain from receptive anal intercourse for 1 week after study visit 2
(4-16 weeks after the screening visit) and study visit 4 (5-26 weeks after the
screening visit)

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 for rectal biopsies, including
but not limited to:

1. Hemoglobin (Hbg) ≤ 10 g/dL

2. Partial thromboplastin time (PTT) > 1.5x upper limit normal (ULN) or
international normalized ratio (INR) > 1.5x ULN

3. Platelet count <100,000

- 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 nonsteroidal anti-inflammatory drugs (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 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