A Phase II Randomized, Double-Blind, Study of the Safety and Tolerability of Maraviroc (MVC), Maraviroc + Emtricitabine (MVC+FTC), Maraviroc + Tenofovir Disoproxil Fumarate (MVC+TDF), or Tenofovir Disoproxil Fumarate + Emtricitabine (TDF+FTC) For Pre-Exposure Prophylaxis (PrEP) To Prevent HIV Transmission in At-Risk Men Who Have Sex With Men and in At-Risk Women

National Institute of Allergy and Infectious Diseases (NIAID)13 sites in 2 countries594 target enrollmentJune 2012

InterventionsMaraviroc Emtricitabine placebo Tenofovir disoproxil fumarate placebo Emtricitabine Tenofovir disoproxil fumarate Maraviroc placebo

DrugsMaraviroc Emtricitabine Tenofovir disoproxil fumarate

Overview

Phase: Phase 2
Intervention: Maraviroc
Conditions: HIV Infection
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Enrollment: 594
Locations: 13
Primary Endpoint: Occurrence of Grade 3 or Higher Adverse Events (AEs)
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Pre-exposure prophylaxis (PrEP) is a method of preventing HIV infection through the use of antiretroviral (ARV) medications before exposure to HIV. This study will evaluate the safety and tolerability of four ARV regimens in preventing HIV infection in men who have sex with men who may be at risk of getting HIV infection through sex and women who may be at risk of getting HIV infection through sex. The four ARV regimens being evaluated are maraviroc (MVC), MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. The MVC-containing arms will be compared to TDF/FTC alone and in combination.

Detailed Description

Several clinical trials are currently under way evaluating the safety and efficacy of ARV-based PrEP for preventing HIV infection. In 2010, the results of the first efficacy trial of ARV-based PrEP showed 44% fewer HIV infections among study participants receiving the study drugs (TDF and FTC) than among those receiving placebo. Although these results are promising, concerns about poor adherence, drug resistance, and toxicity prompt further exploration of ARV PrEP regimens. This trial will evaluate the safety and tolerability of PrEP using four ARV regimens in reducing HIV transmission in at-risk men who have sex with men and in at-risk women. Participants will be randomly assigned to one of four arms: Arm 1, Arm 2, Arm 3, or Arm 4. Arm 1 will receive MVC, FTC placebo, and TDF placebo orally once daily from Week 0 through 48. Arm 2 will receive MVC, FTC, and TDF placebo orally once daily from Week 0 through 48. Arm 3 will receive MVC, FTC placebo, and TDF orally once daily from Week 0 through 48. Participants in Arm 4 will receive MVC placebo, FTC, and TDF orally once daily from Week 0 through 48. Study visits will occur at enrollment and Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 49. All study visits will include a physical examination, blood collection and storage, and HIV counseling and testing. Select study visits will include adherence counseling, surveys, behavioral assessments (including sexual behavioral assessments), urine collection, and dual-energy x-ray absorptiometry (DXA). Participants will also undergo sexual behavioral assessments randomly 12 to 13 times through Week 48 via short message service (SMS). Some female participants may opt into taking part in an interview at Week 48. Participants who enroll in this study may also consent to be a part of two subset evaluations as part of this study: the Drug Interaction Subset or the Tissue Subset. Enrollment in these subsets will involve additional study procedures. The Drug Interaction Subset will undergo blood collection before and after a directly observed dose of study drug at the Week 2 visit. Participants in the Tissue Subset will take part in additional study procedures at select visits, including blood collection, hair collection, and rectal tissue and fluid collection (required for men; optional for women). Women involved in the Tissue Subset will also undergo cervical tissue and cervicovaginal fluid collection at select visits.

Registry

clinicaltrials.gov

Start Date

June 2012

End Date

November 2015

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•For participants in the men's component of the study, born male. For participants in the women's component of the study, born female.
•18 years or older at the time of screening
•Willing to provide informed consent for the study
•Able to read at a level required for the study components (e.g., computer-assisted self-interview \[CASI\] and short message service \[SMS\], per the judgment of the study investigator)
•For men, a history of receptive or insertive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report)
•For women, a history of vaginal intercourse or receptive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report)
•The following laboratory values must be from specimens obtained within 45 days prior to study enrollment: Nonreactive HIV test results (more information on this criterion can be found in the protocol); hemoglobin (men) greater than 11 g/dL; hemoglobin (women) greater than or equal to 10.5 g/dL; absolute neutrophil count greater than 750 cells/mm\^3; platelet count greater than or equal to 100,000/mm\^3; for men and women, calculated creatinine clearance greater than or equal to 70 mL/minute using the Cockcroft-Gault equation; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal (ULN); total bilirubin less than 2.5 ULN; urine protein less than 2+; and hepatitis B surface antigen (HBsAg) negative.
•No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records)
•No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records)
•Willing to undergo all required study procedures (including sexual assessment by CASI, use of the drug monitoring device, and SMS \[i.e., texting\])

Exclusion Criteria

•One or more reactive HIV test results at screening or enrollment, even if HIV infection is not confirmed
•Coenrollment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrollment and receipt of active arm (i.e., NOT a placebo) of an HIV vaccine trial (provided by available documentation)
•Use of ARV therapy (e.g., for post-exposure prophylaxis \[PEP\] or PrEP) in the 90 days prior to study entry
•Prior history of a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption (provided by self-report or obtained from medical history or records)
•Receipt of prohibited medications as described in the study drug package inserts or listed in the Study-Specific Populations (SSP) Manual (provided by self-report or obtained from medical history or medical records)
•Ongoing intravenous drug use: episodic use or any use in the past 90 days (as assessed by the study investigator)
•Known medical history of allergy to soy (soya or soybeans) or peanuts
•Weight exceeding 300 pounds (exceeds weight limit of DXA scanners)
•For women, pregnancy or currently breastfeeding
•Exclusion Criteria for the Tissue Subset: