Clinical trial NCT02333045: Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women
Official title: Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: HIV
Keywords: HIV-negative
Women
At-risk
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2015-01-07
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study seeks to understand the immune cells in the cervical fluid of in the blood and genital tract 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Count of Total Cells Obtained From Cervicovaginal Lavage Samples
timeFrame: Baseline, Day 7, Day 14, Day 21
Secondary outcomes:
measure: Steady-state Area Under the Plasma Concentration-time Curve of Study Drug
timeFrame: 7 days
measure: Steady-state Area Under the Female Genital Tract Concentration-time Curve of Study Drug
timeFrame: 7 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Infectious Diseases Clinic (Ponce Clinic)
state: Georgia
Study officials:
affiliation: Emory University
name: Anandi Sheth, MD
role: PRINCIPAL_INVESTIGATOR
References: