Safety, tolerability study to enroll MSM in the United States and Puerto Rico
Scientists are launching the first clinical trial to test whether drug regimens containing maraviroc, a medication currently approved to treat HIV infection, are also safe and tolerable when taken once daily by HIV-uninfected individuals at increased risk for acquiring HIV infection. The eventual goal is to see if the drug regimens can reduce the risk of infection.
The trial involves a strategy known as pre-exposure prophylaxis, or PrEP, in which HIV-uninfected individuals who are at risk for contracting the virus take one or two HIV drugs routinely in an effort to prevent infection. Called Novel Exploration of Therapeutics for PrEP, or NEXT-PrEP, the two-year study is sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
"The NEXT-PrEP study will examine whether maraviroc-based PrEP is safe and well-tolerated. It is a necessary first step before we can test the effectiveness of maraviroc-based PrEP, and in the future, potentially expand the selection of drugs that may be used in this emerging HIV prevention strategy," said NIAID Director Anthony S. Fauci, M.D.
Led by principal investigator Roy M. Gulick, M.D., M.P.H., chief of the Division of Infectious Diseases and professor of medicine at Weill Cornell Medical College of Cornell University, the study team will enroll 400 HIV-uninfected men who have sex with men (MSM) ages 18 and older in 12 cities in the United States and Puerto Rico. The volunteers will be assigned at random to take one of the following four PrEP study regimens daily for 48 weeks:
Placebo pills will be added to the regimens as needed so that neither the participants nor the study team will know who is taking which regimen. The investigators will observe whether the volunteers experience any serious side effects and assess whether they continue taking their PrEP regimens as recommended. If the study drugs appear to compromise a participant's health, he will be directed to stop taking them.
All participants will regularly be tested for HIV infection and receive condoms and counseling on how to reduce their risk of becoming infected with the virus.
The NIH-funded HIV Prevention Trials Network (HPTN), in collaboration with the AIDS Clinical Trials Group (ACTG), is conducting the NEXT-PrEP study, also called HPTN 069/ACTG 5305. Gilead Sciences Inc. of Foster City, Calif., and ViiV Healthcare of Brentford, England, are donating the study drugs.
This trial builds on the results of the NIAID-sponsored iPrEx study, which found in 2010 that the daily PrEP regimen of oral tenofovir plus emtricitabine (brand name Truvada) reduced the risk of HIV infection in MSM by 43.8 percent.
The NEXT-PrEP study leaders chose to examine PrEP regimens containing maraviroc (brand name Selzentry) for several reasons. All other PrEP regimens tested to date involve tenofovir alone or in combination with emtricitabine. Concerns about potential toxicity and the development of drug resistance suggested to the scientists that a wider array of antiretroviral drugs with optimal properties for HIV prevention should be explored.
Maraviroc, manufactured by ViiV Healthcare, was approved by the U.S. Food and Drug Administration in 2007 to treat HIV/AIDS and has continued to demonstrate safety and effectiveness in HIV-infected individuals. The drug prevents HIV from entering cells, unlike tenofovir and emtricitabine, which interfere with HIV replication after the virus has infected a cell. Maraviroc rarely engenders resistance and although approved in the U.S. for use in patients beginning HIV treatment, it is not commonly used this way in a clinical setting.
For additional information about the NEXT-PrEP study, see the NEXT-PrEP Q&A. Information about the clinical trial is also available at http://www.clinicaltrials.gov under the identifier NCT01505114.
This study is being funded by grants numbers 5UM1AI068613-07, 5UM1AI068617-07 5UM1AI068619-07, 5UM1AI069465-06, 5UM1AI069466-06, 5UM1AI069480-05, and 5UM1AI069503-06 to HPTN; grants numbers 5UM1AI069415-06, 5UM1AI069419-06, 5UM1AI069424-06, 5UM1AI069434-06, 5UM1AI069494-06, 5UM1AI069501-06 and 5 UM1AI069534-06 to ACTG; and grant number 5UM1AI069423-06 to HPTN and ACTG jointly.
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