Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women

In this study, the investigator seeks to understand the immune cells in the cervical fluid of
HIV-negative healthy female volunteers, and to see if these cells can be modified using a
combined anti-viral and antiinflammatory drug called maraviroc, a medicine used in the
treatment of HIV infection. Maraviroc works by preventing HIV from entering human immune
cells by blocking a protein on the outside of these cells called the C-C chemokine receptor
type 5 (CCR5) receptor. When maraviroc is bound to this protein, the virus cannot enter the
cell. The investigator thinks that CCR5 antagonists could be particularly good drugs for HIV
pre-exposure prophylaxis (PrEP) and could potentially be dosed in ways that are easier to
take than the current drugs used for PrEP.

In order to further evaluate this PrEP strategy, the investigator will first study the immune
cells in the blood and genital tract of HIV-negative healthy female volunteers over the
course of 3 months to see how these cells change over time and are affected by factors such
as age, menstrual cycle, and genital infections.

The amount of maraviroc compared with the drugs in the current drugs used for PrEP
(tenofovir/ emtricitabine) in the blood and genital tract of HIV-negative healthy female
volunteers before, during, and after they are given maraviroc versus tenofovir/ emtricitabine
for 7 days will be measured. We will also study immune cells from the blood and genital tract
from these women to see if maraviroc, tenofovir, or emtricitabine have an effect on these
cells that would prevent them from becoming infected with HIV.

Inclusion Criteria:

- Age 18-44 years

- Must be biologically female (defined as sex at birth)

- HIV negative women with at least one of the following risk factors in the past 5 years

1. Injection drug use or use of crack, cocaine, heroin, or methamphetamine

2. Diagnosed with a sexually transmitted infection

3. Unprotected sex with 3 or more men

4. Having sex for drugs, money, or shelter

5. Sex with a known HIV-positive man

6. Having a partner meeting any of the preceding criteria

- Normal menses (within 22-35 day intervals) for at least 3 cycles

- No history of alcohol abuse, heart disease, or liver disease, or any other medical
condition that would interfere with the conduct of the study, in the opinion of the
study investigator

- No history of loop electrosurgical excision procedure (LEEP), conization, or
cryosurgery

- Normal chemistry, liver function, and complete blood count panels at screening,
including:

1. Absolute neutrophil count (ANC) ≥ 750/mm3

2. Hemoglobin ≥ 10.0 g/dL

3. Platelet count ≥ 100,000/mm3

4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
phosphatase ≤ 3 x Upper Limit Normal (ULN)

5. Total bilirubin ≤ 2.5 x ULN

6. Creatinine Clearance (CrCl) ≥ 60 mL/min as estimated by the Cockcroft-Gault
equation

- Negative hepatitis B surface antigen (HBsAg)

- No signs or symptoms of orthostasis

- No signs or symptoms of vaginal infection or genital ulcer disease at screening or
untreated vaginal infection in the last 30 days

- Not receiving concurrent medications that interact with maraviroc (MVC) or any
antiretrovirals (such as tenofovir/ emtricitabine [Truvada®]) for the purpose of HIV
prevention

- Willing to use condoms for the duration of the study and abstain from sexual
intercourse for 48 hours before each genital tract sampling

Exclusion Criteria:

- Male sex (defined as sex at birth)

- Pregnant or breastfeeding

- Current use of systemic hormonal contraception

- Symptomatic vaginal infection or genital ulcer disease at screening or treatment for
vaginal infection in the last two weeks

- Active malignancy for which the participant is undergoing evaluation and/or treatment

- Immunosuppressive medications (i.e, systemic steroids)

- Any surgery in the preceding 2 months