ENLIGHTEN: Establishing Novel Antiretroviral Imaging for Hair to Elucidate Non-Adherence

Details:

Participants will be sequentially assigned to enroll in dosing arm, beginning with Maraviroc,
then Dolutegravir and ending with Tenofovir/Emtricitabine, Participation will last
approximately 3 months and will include a screening visit, three 28-day phases, and a
follow-up safety visit.

Phase 1 consists of a 28-day study period with a single dose of study product on Day 0.

Phase 2 consists of a 28-day study period with each subject receiving a single daily observed
dose of study product beginning on Day 0.

Phase 3 consists of a 28-day study period, with three randomized drug-dosing schemas
beginning on Day 0. Participants will either: stop taking their study product, dose once per
week, or dose three times per week.

Participants will return to the clinic for hair and blood sampling on days 3/7/14/21/28
post-dose for all three phases. Adverse events will be assessed at every visit. Safety labs
will be drawn at the midpoint and at the end of each study phase, and at any time indicated
due to suspected adverse events.

Description of Study Phases Screening: Participants will be recruited from a variety of
advertisements, and pre-screened using a telephone IRB-approved questionnaire. If
participants are interested and pass the initial screening, a screening study visit in the
research center will be scheduled. This visit should take approximately 90 minutes, during
which full physical examination and medical history will be obtained, as well as physical
diagnostics to assess for eligibility. This visit must be completed within the 28 days prior
to enrollment.

Phase 1: Consists of a 28-day study period, with a single dose of study product on Day 0
(Maraviroc, Dolutegravir, or tenofovir/emtricitabine). Day 0 can be scheduled on either
Mondays or Tuesdays, and once eligibility is confirmed on the day of enrollment, a witnessed
dose of study product will be administered. Participants will return to the clinic for hair
and blood sampling on Days 3/7/14/21/28 days post-dose. Adverse events will be assessed at
every visit. Safety labs will be drawn at the midpoint and at the end of the study phase, and
at any time indicated due to suspected adverse events. These visits should last less than 30
minutes.

Phase 2: Consists of a 28-day study period, with each subject receiving a single daily
observed dose of study product beginning on Day 0. Day 0 can be scheduled on either Mondays
or Tuesdays, once continued eligibility is confirmed. Target scheduling will have Phase 2
begin within 2 weeks of completing Phase 1, but could be extended up to 28 days as clinic
availability dictates. Participants will return to the clinic daily for dosing, and for hair
and blood sampling on Days 3/7/14/21/28 days post-dose. Adverse events will be assessed at
every visit. Safety labs will be drawn at the midpoint, and at the end of the study phase,
and at any time indicated due to adverse events. These visits should last less than 30
minutes. Dosing only visits should last less than 5 minutes.

Phase 3: Consists of a 28-day study period, with three randomized drug-dosing schemas. Day 0
can be scheduled on Mondays, Tuesdays or Fridays, once continued eligibility is confirmed.
Target scheduling will have Phase 3 begin as soon as possible after completing Phase 2, on a
Monday/Tuesday/Or Friday within the week. On Day 0, participants will be randomized to one of
3 potential dosing schemes:

1. No further doses

2. One dose weekly (Day 0, 7, 14, 21) 4 doses

3. Three Doses weekly (Mondays, Wednesdays, Fridays) (Days 0, 2, 4, 7, 9, 11, 14, 16, 18,
21, 23, 25) 12 doses

Participants will return to clinic for observed dosing as scheduled, and for hair and blood
sampling on days 3/7/14/21/28). Safety labs will be drawn at the midpoint, at the end, and at
any time indicated due to adverse events. These visits should last less than 30 minutes.
Dosing only visits should last less than five minutes.

Inclusion Criteria

- Healthy volunteer between the ages of 18 and 70, inclusive on the date of screening,
with an intact gastrointestinal tract. Healthy is defined as no clinically relevant
abnormalities identified by a detailed medical history, full physical examination,
including blood pressure and pulse rate measurement, and clinical laboratory tests

- Recent medical history in good medical standing, without evidence of fever five days
prior to enrollment

- HIV-negative

- Able to swallow pills

- Has minimum hair required to provide study samples

- Not allergic to any component of the study drug

- Signed and dated informed consent indicating that they have been informed of all
pertinent details of the trial and are willing to participate

- Willing and able to comply with scheduled visits, laboratory tests and trial
procedures

- Willing to use at least one form of acceptable birth control throughout the duration
of the study

- Negative, or receiving treatment, for syphilis at screening

- Hemoglobin Grade 2 or lower, with no clinically significant medical issues that would
preclude blood sampling

Exclusion Criteria

- Age outside of desired range

- Confirmed positive results for HIV, Hepatitis B or C at screening

- Subjects of all genders actively involved in the conception process, in addition to
cisgender female subjects who are in the immediate post-partum period or breastfeeding

- Insufficient amount of hair or unwilling to keep hair length at least 1 centimeter
throughout duration of study

- Unable or unwilling to comply with all lifestyle measures and/or visits

- Impaired renal function, as documented by a creatinine clearance <80 mL/min with the
Cockcroft-Gault equation

- Has donated blood within the past 56 days in the amount greater than 500 mL

- Has taken an investigational drug in the past 4 months

- Clinical, laboratory, or surgical abnormalities that would preclude sample collection

- Has a condition, which, in the opinion of the investigator, is likely to interfere
with follow-up or ability to take the study medication appropriately

- Any clinically significant laboratory result Grade 2 or greater according to the DAIDS
Laboratory Grading Tables

- History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150
mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week