Examining Hair to Determine Tenofovir Exposure

Pre-exposure prophylaxis (PrEP) is a new strategy for the prevention of HIV infection. It
involves providing antiretroviral medications—those that treat HIV infections—to people
before they are exposed to HIV. In clinical trials of PrEP, several of which are currently
under way, accurate measurements are needed of how much exposure participants have to the
PrEP medications. Current methods, such as self-reports of medication adherence or pill
counting, can lead to inaccurate readings of PrEP exposure because participants may forget
to take pills and individual differences may affect levels of exposure. Measuring PrEP
exposure levels in hair yields an objective marker of exposure that is not subject to
self-report errors and that takes into account individual differences. This study will test
the use of a hair sample for assessing the level of exposure to tenofovir disoproxil
fumarate (TDF), an antiretroviral medication, in people not infected with HIV.

Participation in this study will last 9 months. Participants will undergo baseline testing
and then will be randomly assigned to begin one of three conditions, based on dosing
schedule: receiving TDF 2, 4, or 7 days per week. All participants will complete each of
these dosing schedules, but the order in which they are completed will be randomly assigned.
Each dosing schedule will last 6 weeks, with a break of several weeks between them. During
each dosing schedule, study staff will confirm that participants are taking each scheduled
dose by watching them take the pills on weekdays and calling them on weekends. Follow-up
visits will occur at Days 1, 21, and 42 of each dosing schedule. During the baseline and
follow-up visits, the following will be completed: an HIV rapid test; counseling about HIV
prevention; a brief physical exam; a talk with a staff member about health, symptoms, and
other medications; a blood draw, which will be used for several tests; collection of a urine
sample and pregnancy test; and optional donation of a sample of pubic hair. On the last day
of each dosing schedule, a small sample of hair will be cut from each participant's scalp.
An additional follow-up visit will occur after participants complete 4 weeks of the 7-day
dosing schedule. This visit will last 24 hours and will involve collection of additional
blood samples.

Inclusion Criteria:

- Ability to speak English

- HIV-1 uninfected, based on HIV rapid testing performed during screening and
enrollment

- Calculated creatinine clearance greater than or equal to 60 mL/min by the
Cockcroft-Gault creatinine clearance formula

- Serum creatinine less than or equal to the site laboratory upper limit of normal

- Urine dipstick with negative or trace result for both glucose and protein

- Negative urine beta human chorionic gonadotropin (beta-HCG) test for women

- Adequate hepatic function, defined as total bilirubin and hepatic transaminases (ALT
and AST) less than or equal to twice the upper limit of normal

- Adequate hematologic function, defined as an absolute neutrophil count greater than
or equal to 1,500/mm3, platelet count greater than or equal to 100,000/mm3, and
hemoglobin greater than or equal to 10 g/dL

- Ability to participate in modified directly observed dosing of study drug

- Ability to provide a personal cell phone number to be contacted on for unobserved
modified directly observed therapy (mDOT) visits

- Minimum length of 3 cm scalp hair in occipital region

- Willing to provide hair and plasma samples as specified by the protocol

- Dark hair (brown or black), as assessed by the study clinician

- Volunteers born female must agree to consistently use effective contraception from at
least 21 days prior to enrollment through the last protocol visit for sexual activity
that could lead to pregnancy and agree not to seek pregnancy through alternative
methods, such as artificial insemination or in vitro fertilization until after the
last scheduled protocol visit.

Exclusion Criteria:

- Active and serious medical problems, including heart or lung disease, diabetes
requiring hypoglycemia medications, previously diagnosed malignancies expected to
require further treatment, and serious infections

- Hepatitis B surface antigen positivity

- History of chronic kidney disease

- Known osteoporosis, osteomalacia, or osteopenia

- History of pathological bone fractures not related to trauma

- Receiving ongoing therapy with any of the following: antiretroviral therapy,
interferon or interleukin therapy, aminoglycoside antibiotics, amphotericin B,
cidofovir, systemic chemotherapeutic agents, other agents with significant
nephrotoxic potential, other agents that may inhibit or compete for elimination via
active renal tubular secretion (e.g., probenecid), or other investigational agents

- Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting
that may confer an inability to receive an orally administered medication

- Use of hair dyes or hair permanent products in the last 3 months (streaking is
acceptable)

- Current participation in any other research study involving drugs, investigational
agents, or medical devices

- Breastfeeding at screening or enrollment, per participant report

- Active alcohol or drug use considered sufficient by clinician to hinder compliance
with study procedures

- Elevated risk of HIV infection, as defined in the study protocol

- At enrollment, has any social or medical condition that, in the investigator's
opinion, would preclude provision of informed consent, make participation in the
study unsafe, complicate interpretation of study outcome data, or otherwise interfere
with achieving the study objectives