Rectal Microbicide Safety and Acceptability Trial of Topically Applied Tenofovir Compared With Oral Tablet

Inclusion Criteria

1. ≥ Age of 18 at screening

2. Willing and able to provide written informed consent for screening and enrollment

3. HIV-1 uninfected at screening according to the standard DAIDS algorithm in Appendix
II

4. Willing and able to communicate in English

5. Willing and able to provide adequate locator information, as defined in site standard
operating procedures (SOP)

6. Availability to return for all study visits, barring unforeseen circumstances

7. Per participant report at screening, a history of consensual RAI at least once in the
prior year

8. Willing to abstain from insertion of anything rectally including sex toys, other than
the study gel during the active phases of the study and for 5 days following biopsy
collection

9. Willing to abstain from sexual intercourse (rectal and vaginal) during the active
phases of the study and for 5 days following biopsy collection

10. Must agree to use study provided condoms for the duration of the study for vaginal
and insertive anal intercourse

11. Must be in general good health

12. Must agree not to participate in other drug trials

In addition to the criteria listed above, female participants must meet the following
criteria:

13. Post-menopausal or using (or willing to use) an acceptable form of contraception
(e.g., barrier method, IUD, hormonal contraception, surgical sterilization, or
vasectomization of male partner). If the female participant has female partners only,
the method of contraception will be noted as a barrier method in the study
documentation.

Exclusion Criteria

1. Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which
in the opinion of the clinician represents a contraindication to biopsy (including
but not limited to presence of any unresolved injury, infectious or inflammatory
condition of the local mucosa, and presence of symptomatic external hemorrhoids)

2. At screening, clinical or laboratory diagnosis of active rectal or reproductive tract
infection requiring treatment per current Centers for Disease Control and Prevention
(CDC) guidelines or urinary tract infection (UTI). Infections requiring treatment
include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, other
vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active HSV
lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis,
or symptomatic genital warts requiring treatment. Note that HSV-2 seropositive with
no active lesions is allowed, since treatment is not required.

Note: Allow one re-screening after documented treatment (30 days) in cases of GC/CT
identified at screening

3. At screening:

1. Positive for hepatitis B surface antigen

2. Hemoglobin < 10.0 g/dL

3. Platelet count < 100,000/mm3

4. White blood cell count less than 2,000 cells/mm3 or > than 15,000 cells/mm3

5. Calculated creatinine clearance less than 80 mL/min by the Cockcroft-Gault
formula where creatinine clearance in mL/min (140- age in years) x (weight in
kg) x (0.85 for females)/72 x (serum creatinine in mg/dL)

6. Serum creatinine > 1.3× the site laboratory upper limit of normal (ULN)

7. ALT and/or AST > 2.5× the site laboratory ULN

8. +1 glucose or +1 protein on urinalysis (UA)

9. History of bleeding problems (i.e. INR > 1.5× the site laboratory ULN or PTT >
1.25× the site laboratory ULN)

4. History of significant gastrointestinal bleeding in the opinion of the investigator

5. Allergy to methylparaben, propylparaben, sorbic acid

6. By participant report at enrollment, history of excessive daily alcohol use (as
defined by the CDC as heavy drinking consisting of an average consumption of more
than 2 drinks per day for men, and more than 1 drink per day for women), frequent
binge drinking or illicit drug use that includes any injection drugs,
methamphetamines (crystal meth), heroin, or cocaine including crack cocaine, within
the past 12 months

7. Per participant report at screening, anticipated use and/or unwillingness to abstain
from the following medications during the period of study participation:

1. Heparin, including Lovenox®

2. Warfarin

3. Plavix® (clopidogrel bisulfate)]

4. Rectally administered medications (including over-the-counter products)

5. Aspirin

6. NSAIDS

7. Acyclovir

8. Valacyclovir

9. TDF

10. Any other drugs that are associated with increased likelihood of bleeding
following mucosal biopsy

8. By participant report at screening, use of systemic immunomodulatory medications,
rectally administered medications, rectally administered products (including condoms)
containing N-9, or any investigational products within the 4 weeks prior to the
Enrollment/Baseline Evaluation Visit

9. History of recurrent urticaria

10. Any other condition or prior therapy that, in the opinion of the investigator, would
preclude informed consent, make study participation unsafe, make the individual
unsuitable for the study or unable to comply with the study requirements. Such
conditions may include, but are not limited to, current or recent history of severe,
progressive, or uncontrolled substance abuse, or renal, hepatic, hematological,
gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.

In addition to the criteria listed above, female participants will be excluded if
they meet any of the following criteria:

11. Pregnant at Enrollment/Baseline Evaluation Visit

12. Breastfeeding or intent to breastfeed during duration of study