Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women

Study Overview
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Brief Summary
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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
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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.

Official Title
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Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women

Conditions
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HIV

Intervention / Treatment
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* Drug: Truvada qd
* Drug: Maraviroc 300 qd


Participation Criteria
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Eligibility Criteria
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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 Injection drug use or use of crack, cocaine, heroin, or methamphetamine Diagnosed with a sexually transmitted infection Unprotected sex with 3 or more men Having sex for drugs, money, or shelter Sex with a known HIV-positive man 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: Absolute neutrophil count (ANC) ≥ 750/mm3 Hemoglobin ≥ 10.0 g/dL Platelet count ≥ 100,000/mm3 Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 3 x Upper Limit Normal (ULN) Total bilirubin ≤ 2.5 x ULN 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Truvada qd<br>Women will be assigned at random Truvada 1 tablet PO daily | Drug: Truvada qd<br>* Truvada 1 tablet PO daily for 7 days<br>* Other names: Truvada;|
| Experimental: Maraviroc 300 qd<br>Women will be assigned at random Maraviroc 300 mg PO daily | Drug: Maraviroc 300 qd<br>* Maraviroc 300 mg PO daily for 7 days<br>* Other names: Selzentry;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Total Cells Obtained From Cervicovaginal Lavage Samples | The count of CCR5+CD4+ T cells in the genital tract, before participants began study treatment, after 7 days of treatment, and during the post-treatment drug elimination period. The precise role of CCR5+CD4+ T cells in the female genital tract is unknown, however, higher cell counts may suggest the potential for more HIV target cells in the genital tract. | Baseline, Day 7, Day 14, Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady-state Area Under the Plasma Concentration-time Curve of Study Drug | Study drug concentrations will be measured from blood. | 7 days | 
| Steady-state Area Under the Female Genital Tract Concentration-time Curve of Study Drug | Study drug concentrations will be measured from female genital tract. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-negative, Women, At-risk