Clinical Trials

MainTitle

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

This study has been terminated
( Minimal efficacy of maraviroc alone was found in preliminary data analysis of another study. )

Sponsor
Emory University


Information provided by (Responsible Party)
Anandi Sheth, Emory University

ClinicalTrials.gov Identifier
NCT02333045

First received: January 5, 2015
Last updated: December 19, 2017
Last Verified: December 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention
HIV

Drug : Truvada qd
Drug : Maraviroc 300 qd

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Characterization and Modulation of Mucosal Immunity for HIV Prevention in Women

Further study details as provided by Anandi Sheth, Emory University:

Primary Outcome Measures

  • Count of Total Cells Obtained From Cervicovaginal Lavage Samples [ Time Frame: Baseline, Day 7, Day 14, Day 21 ]
    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.
Secondary Outcome Measures:
  • Steady-state Area Under the Plasma Concentration-time Curve of Study Drug [ Time Frame: 7 days ]
    Study drug concentrations will be measured from blood.
  • Steady-state Area Under the Female Genital Tract Concentration-time Curve of Study Drug [ Time Frame: 7 days ]
    Study drug concentrations will be measured from female genital tract.

Enrollment: 4
Study Start Date: January 2015
Study Completion Date: October 28, 2016
Estimated Primary Completion Date: October 28, 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 Name: 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 Name: Selzentry

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

Eligibility

Ages Eligible for Study: 18 Years to 44 Years  
Sexes Eligible for Study: Female  
Accepts Healthy Volunteers: Yes  

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02333045

Locations

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

Sponsors and Collaborators

Emory University

Investigators

Principal Investigator: Anandi Sheth, MD Emory University
More Information

More Information


Responsible Party: Anandi Sheth, Assistant Professor, Emory University  
ClinicalTrials.gov Identifier: NCT02333045   History of Changes  
Other Study ID Numbers: IRB00074767  
Study First Received: January 5, 2015  
Last Updated: December 19, 2017  

Keywords provided by Anandi Sheth, Emory University:

HIV-negative
Women
At-risk

Additional relevant MeSH terms:
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Maraviroc

ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.