The ADAPT Study: Use of Emtricitabine and Tenofovir Disoproxil Fumarate for Pre-Exposure Prophylaxis (PrEP)

No single strategy for the prevention of HIV has emerged as consistently used and
successful, so multiple strategies have been developed. PrEP involves delivering ARV
medications to people before they are exposed to HIV, in order to prevent infection. The
optimal method of delivering PrEP has not yet been determined. This study will examine the
feasibility of delivering PrEP in three methods. Daily dosing involves receiving ARV
medications every day; time-driven dosing involves receiving ARV medications twice weekly
plus a post-exposure dose; and event-driven dosing involves receiving ARV medications before
and after a potential exposure to HIV. The ARV medication that will be used in this study is
a combination pill that contains emtricitabine and tenofovir disoproxil fumarate (FTC/TDF).
Recent research studies have shown that, if taken consistently, a daily oral dose of FTC/TDF
can reduce the risk of HIV infection.

This study will enroll HIV-uninfected men who have sex with men and transgender women
(MSM/TGW) and women who have sex with men (WSM). Participation will last 34 weeks. All
participants will be given a combination pill that contains FTC/TDF. For the first 5 weeks,
all participants will come to the study clinic weekly to receive a single dose of FTC/TDF.

At Week 6, participants will be randomly assigned to one of three groups. In the daily
dosing group, participants will take FTC/TDF once a day. In the time-dosing group,
participants will take FTC/TDF twice per week and another dose after sexual intercourse (a
post-exposure dose). In the event-dosing group, participants will take FTC/TDF before and
after sexual intercourse. During this part of the study, participants will be given FTC/TDF
to take on their own. Every week, from Week 6 to Week 29, study officials will call to ask
questions about how many pills participants have taken and when they have had sexual
intercourse. Participants will also complete computer-assisted self-interviews (CASIs).

Study visits will occur at enrollment, once a week for the first 5 weeks, and then once a
month until Week 34. Assessment will include recording of medical history, completing an
interview about sexual practices and background, and collection of blood, urine, and hair
samples. Select study visits will include vaginal practices assessment (including use of
lubricants and vaginal cleansing practices), family planning assessments (for women), and
sex hormones assessments (for men).

Participants who acquire HIV infection during the study will discontinue study product.
These participants will continue to be followed after enrollment at Weeks 4, 6, 10, 14, 18,
22, 26, 30, and every 12 weeks thereafter, as appropriate, until the last study participant
completes follow-up at the study site. Participants whose first reactive HIV rapid test is
at Week 34 who are later confirmed to be HIV infected will also be followed every 12 weeks
after their Week 30 visit until the last study participant completes follow-up at the study
site. Participants who acquire HIV infection during the study will undergo select protocol
procedures and will receive counseling and referrals for HIV treatment.

Inclusion Criteria:

- Literacy in one of the study languages (Thai, Xhosa, and/or English)

- Able to provide written informed consent

- Able to provide weekly telephonic updates

- Within 70 days of enrollment:

1. Serum creatinine less than or equal to the upper limit of normal (ULN) and
calculated creatinine clearance of at least 70 mL/min by the Cockcroft-Gault
formula. More information on this criterion can be found in the protocol.

2. Serum phosphate greater than or equal to the lower limit of normal (LLN)

3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
equal to 2 times ULN

4. Hemoglobin greater than 10 g/dL

5. Hepatitis B surface antigen (HBsAg)-negative

6. Willing and able to provide adequate locator information

Inclusion Criteria for MSM/TGW:

- Male at birth

- Reporting anal intercourse and/or receptive neovaginal intercourse with at least one
man or transgender woman in the past 6 months

- One or more of the following risk factors for HIV acquisition in the past 6 months
according to self-report: sexual intercourse with more than one man or transgender
woman; history of an acute sexually transmitted infection (STI); sex in exchange for
money, goods, or favors; condomless intercourse (oral, anal, vaginal, or neovaginal)
with a partner known to be HIV-infected or of unknown HIV infection status according
to self report

Inclusion Criteria for Women Who Have Sex With Men (WSM):

- Female at birth or self identify as female

- Not pregnant or breastfeeding

- Not able to or not intending to become pregnant during the next year

- If able to become pregnant, self reported use of an effective method of contraception
at Enrollment, and intending to use an effective method for the next 34 weeks

- One or more of the following risk factors for HIV acquisition in the past 6 months
according to self report: sexual intercourse with more than one man; history of an
acute STI; sex in exchange for money, goods or favors; condomless intercourse (oral,
anal, or vaginal) with a partner known to be HIV-infected or of unknown HIV infection
status

Exclusion Criteria:

- Proteinuria 2+ or greater at screening

- Glucosuria 2+ or greater at screening

- Serious and active medical or mental illness

- One or both HIV rapid tests is reactive at screening or enrollment, regardless of
subsequent HIV diagnostic test results

- Signs or symptoms suggestive of acute HIV infection

- Use of hypoglycemic agents for diabetes or agents with known nephrotoxic potential

- Use of ARV therapy (e.g., for post-exposure prophylaxis [PEP] or PrEP) in the 90 days
prior to study entry

- Serum phosphate level below site laboratory LLN

- Current participation (or participation within 3 months of screening) in any HIV
prevention study

- Previous or current participation in the active arm of an HIV vaccine trial

- Acute or chronic hepatitis B (HBV) infection (refers to chronic active HBV infection
evidenced by a positive test for hepatitis B surface antigen (HBsAg)

- Presence of a psychological or social condition or an addictive disorder that would
preclude compliance with the protocol

- Any other reason or condition that in the opinion of the investigator would interfere
with participation, complicate interpretation of study outcome data, or otherwise
interfere with achieving the study objectives