Clinical trial NCT01505114
Conditions: HIV Infection
Keywords: HIV Prevention PrEP Maraviroc
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2012-06-01; Completion date: 2015-11-01
Enrollment: 594 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: MVC 300 mg plus FTC placebo and TDF placebo orally once daily arm 2: MVC 300 mg plus FTC 200 mg and TDF placebo orally once daily arm 3: MVC 300 mg plus FTC placebo and TDF 300 mg orally once daily arm 4: MVC placebo plus FTC 200 mg and TDF 300 mg orally once daily
Interventions: intervention 1: Maraviroc intervention 2: Emtricitabine intervention 3: Tenofovir disoproxil fumarate intervention 4: Maraviroc placebo intervention 5: Emtricitabine placebo intervention 6: Tenofovir disoproxil fumarate placebo
Intervention descriptions: intervention 1: 300-mg tablet, once daily, from Week 0 through Week 48 intervention 2: 200-mg capsule, once daily, from Week 0 through Week 48 intervention 3: 300-mg tablet, once daily, from Week 0 through Week 48 intervention 4: Once daily from Week 0 through Week 48 intervention 5: Once daily from Week 0 through Week 48 intervention 6: Once daily from Week 0 through Week 48

Protocol documents: