Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women

NCT ID: NCT02333045

Last Updated: 2018-01-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-10-28

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.

Conditions

HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Truvada qd

Women will be assigned at random Truvada 1 tablet PO daily

Group Type: EXPERIMENTAL

Truvada qd

Intervention Type: DRUG

Truvada 1 tablet PO daily for 7 days

Maraviroc 300 qd

Women will be assigned at random Maraviroc 300 mg PO daily

Group Type: EXPERIMENTAL

Maraviroc 300 qd

Intervention Type: DRUG

Maraviroc 300 mg PO daily for 7 days

Interventions

Truvada qd

Truvada 1 tablet PO daily for 7 days

Intervention Type: DRUG

Maraviroc 300 qd

Maraviroc 300 mg PO daily for 7 days

Intervention Type: DRUG

Other Intervention Names

Truvada; Selzentry

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Anandi Sheth

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anandi Sheth, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Grady Infectious Diseases Clinic (Ponce Clinic)

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00074767

Identifier Type: -

Identifier Source: org_study_id