Exploring HIV Entry Blockade as a Pre-exposure Prophylaxis Strategy in Women

NCT01749566 | Completed Phase 1

• 3 other identifiers: IRB00059752KL2TR000455ACTSIKL22012
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which HIV medicines are used by a person before they are exposed to HIV in order to decrease his or her chance of getting infected. In this study, we will investigate a new PrEP strategy in women using a drug called maraviroc, a medicine used in the treatment of HIV infection called a CCR5 antagonist. We hypothesize that maraviroc could be a particularly good drug for PrEP because it achieves high concentrations in the genital tract in women and decreases the number of HIV-susceptible cells in the genital tract, and thus could potentially be dosed in more favorable ways than the current PrEP drugs. In order to further evaluate this PrEP strategy, we plan to measure the amount of maraviroc in the blood and genital tract of HIV-negative healthy female volunteers before, during, and after they are given maraviroc dosed either in the standard (twice a day) or reduced (once a day) dose for 7 days compared with women who are not given maraviroc. We will also study immune cells from the blood and genital tract from these women to see if maravoric has an effect on these cells that would prevent them from becoming infected with HIV.

Conditions

HIV

Keywords

HIV/AIDS, preexposure prophylaxis, women's health

Outcome Measures

Primary Outcomes (1)

• Change in female genital tract maraviroc concentration

  Day 0, 7, 10-12

Secondary Outcomes (3)

• Female genital tract HIV target cells

  Day 0, 7, 10-12, 14, 21

• Female genital tract T cell activation

  Day 0, 7, 10-12, 14, 21

• Vaginal microbiome

  Day 0, 7, 10-12, 14, 21

Study Arms (3)

Group A (standard maraviroc dosing)

ACTIVE COMPARATOR

maraviroc 300mg po bid x 7 days

Drug: maraviroc

Group B (reduced maraviroc dosing)

ACTIVE COMPARATOR

maraviroc 300mg po daily x 7 days

Drug: maraviroc

Group C (no drug)

NO INTERVENTION

No additional drug

Interventions

maraviroc DRUG

Maraviroc administered at standard (300mg po bid) or reduced (300mg po daily) dosing

Also known as: Selzentry

Group A (standard maraviroc dosing); Group B (reduced maraviroc dosing)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female sex, defined by sex at birth
• Age greater than or equal to 18 years
• Negative HIV serology at screening
• Normal menses (within 22-35 day intervals) for at least 3 cycles
• Intact uterus and cervix
• Normal chemistry and CBC panels at screening, including
• Absolute neutrophil count (ANC) greater than 750/mm3
• Hemoglobin greater than 10.0 g/dL
• Platelet count greater than 100,000/mm3
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase less than 3 x upper limit of normal
• Total bilirubin less than 2.5 x upper limit of normal
• CrCl greater than or equal to 60 mL/min as estimated by the Cockcroft- Gault equation
• Negative hepatitis B surface antigen
• Willing to use condoms for the duration of the study and abstain from sexual intercourse for 48 hours before each genital tract sampling
• Able and willing to provide informed consent

You may not qualify if:

• Pregnancy (by clinical history or positive urine pregnancy test at screening)
• Breastfeeding
• Alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study
• History of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery
• Use of systemic hormonal contraception
• Orthostasis at screening, defined as systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within three minutes of standing.
• Known history of heart or liver disease
• Known history of any medical condition that would interfere with conduct of the study, in the opinion of the study investigator
• Symptoms of active vaginal infection at the time of screening, including new ulcerative genital lesions or purulent and/or foul-smelling vaginal discharge
• Visible ulcerative genital lesions or purulent vaginal discharge during speculum pelvic examination performed at the time of screening
• Concomitant use of medications that interact with maraviroc or known allergy to maraviroc

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Grady Infectious Diseases Program

Atlanta, Georgia, 30303, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Anandi Sheth, MD

  Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 9, 2012
• First Posted: December 13, 2012
• Study Start: December 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: July 9, 2015

Record last verified: 2015-07

Locations

US (1)