Clinical trial NCT00458393
Conditions: HIV Infections
Keywords: HIV Chemoprophylaxis Hepatitis Viral human hepatitis HIV Seronegativity
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2007-06-01; Completion date: 2014-02-01
Enrollment: 2499 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether daily use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) can prevent HIV infection in men who also receive HIV counseling, condoms, and treatment for other sexually transmitted infections (STIs).

Detailed description:
The Joint United Nations Programme on AIDS estimates that 14,000 persons are newly infected with HIV every day worldwide; one half of these infections occur in people between the ages of 15 and 24. New infections occur despite widespread awareness of the modes of HIV transmission and the protection afforded by condom use. Effective interventions for HIV prevention are urgently needed. This study will evaluate the safety and efficacy of chemoprophylaxis for HIV prevention in men who have sex with men (MSM) who are at high risk for HIV infection despite using condoms, receiving HIV counseling, and receiving treatment for STIs, particularly hepatitis B virus (HBV) infection. A daily combination dose of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) has been selected for evaluation because it has a well-established safety record in previous studies and was demonstrated to be effective for HIV prevention in primate models. These medications have long half-lives that allow daily dosing and do not have known interactions with hormonal contraception, methadone, or tuberculosis therapies.

Once on the study drug, participants will be followed for a variable length of time, starting within 4 weeks of their screening visit and lasting up to 144 weeks. All participants will be followed for at least 8 weeks after stopping study drug. Participants who are reactive to a Hepatitis B surface antigen (HBsAg) test will be followed for hepatic flares for 16 additional weeks for a total of 24 weeks after stopping study drug. If enrolled in the optional substudy of bone mineral density, fat distribution, and fasting lipids, the participant will be asked to return for one additional visit 24 weeks after stopping study drug. Participants who HIV seroconvert during their participation will also be followed until the end of the study.

All study visits will be at 4 week intervals. At study entry, high risk, HIV uninfected MSM will be randomly assigned to receive either daily FTC/TDF or placebo, in addition to standard HIV counseling, condoms, and sexually transmitted infection (STI) management. The study will closely monitor biological and behavioral safety, including careful analysis of drug resistance, kidney and liver function, and risk behavior.

At the screening visit, participants will undergo HIV antibody and HBV testing, a medical history, a medical exam, blood and urine collection, risk behavior assessment, and STI testing. At study entry, participants will be given study medication; tested for HCV; and offered the HBV vaccine, if applicable. At all study visits, there will be HIV antibody testing, pill counts, adherence checks, study medication distribution, HIV counseling, and condom distribution. A medical history and blood will be taken on selected visits, along with STI testing and treatment if needed. Testing and treatment of STIs will be provided at no cost to the participant.

All study participants will be encouraged to join a substudy that will assess interactions between HBV infection, bone mineral density and fat distribution, and immune function. If enrolled in the substudy, the participant will be asked to return for one additional visit 24 weeks after stopping the study medication. All participants in the substudy will undergo dual energy x-ray absorptiometry (DEXA) scans, and HIV infected participants will undergo additional blood collection.

Sites will have the option of participating in the following four substudies:

The Hair Substudy: Participants who are receiving FTC/TDF will be eligible to enroll. At each 12-week follow-up study visit, hair samples will be collected and questionnaires will be completed.

The Urine Substudy: For all participants who elect to enroll in this substudy, additional testing will occur on blood and urine samples collected at each 24-week follow-up visit. An additional urine collection will occur 8 weeks after participants stop receiving FTC/TDF.

The Semen Substudy: Participants who seroconvert during the study may elect to participate in this substudy. One semen sample will be collected at participants' next study visit when plasma viral load testing is performed.

The Gonorrhea and Chlamydia Substudy: Participants in this substudy will undergo rectal and oropharyngeal swab procedures and urine collection at the 24-week study visit.

After the randomized phase ends, if the daily oral FTC/TDF arm is shown to be beneficial and safe, participants will be given the option of participating in an open label extension phase. During this extension phase, study participants will receive daily oral open-label FTC/TDF, in addition to standard counseling, condoms, and STI management.

Arms: arm 1: Drug. Daily oral tablet of co-formulated 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate (TDF/FTC). arm 2: Drug. Daily oral placebo
Interventions: intervention 1: daily TDF/FTC intervention 2: Placebo
Intervention descriptions: intervention 1: daily oral medication intervention 2: daily oral medication

Protocol documents: