Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women (MIP)

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.

Study Overview

• Status: Terminated
• Conditions: HIV
• Intervention / Treatment: Drug: Truvada qd; Drug: Maraviroc 300 qd

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Atlanta, Georgia, United States, 30308
      • Grady Infectious Diseases Clinic (Ponce Clinic)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Truvada qd; Women will be assigned at random Truvada 1 tablet PO daily	Drug: Truvada qd; Truvada 1 tablet PO daily for 7 days; Other Names: Truvada
Experimental: Maraviroc 300 qd; Women will be assigned at random Maraviroc 300 mg PO daily	Drug: Maraviroc 300 qd; Maraviroc 300 mg PO daily for 7 days; Other Names: Selzentry

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Anandi Sheth, MD, Emory University

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): October 28, 2016
• Study Completion (Actual): October 28, 2016

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimate): January 7, 2015

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: December 19, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Women; At-risk; HIV-negative
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Maraviroc
• Other Study ID Numbers: IRB00074767