Public release date: 4 MARCH, 2014
EMBARGOED until 12:15 P.M. on 4 MARCH, 2014
A Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus.
Contact: Stephanie Sozomenu
The Aaron Diamond AIDS Research Center
New York, NY: Researchers at the Aaron Diamond AIDS Research Center, an affiliate of the Rockefeller University, led by Dr. David Ho, in collaboration with investigators at GlaxoSmithKline, ViiV Healthcare and the Tulane National Primate Research Center have found that a novel long-acting antiretroviral drug can protect against infection with a virus resembling HIV in an animal model that simulates the transmission of HIV via anal intercourse. The drug, GSK1265744 (GSK744), is an integrase inhibitor, whose mechanism of action is to inhibit a viral enzyme from inserting viral DNA into human chromosome, thereby blocking replication of the virus. The findings appear in the journal Science online, at the ScienceExpress website on March 4.
Advances in HIV treatment have dramatically reduced HIV-related morbidity and mortality worldwide; however, the incidence of new infections continues to pose a significant public health challenge. One approach to HIV prevention has been the use of HIV treatment medications to prevent infection. Such use of drugs is called pre-exposure prophylaxis or PrEP. Results of randomized clinical trials testing once-daily oral pills as PrEP have been mixed- with overall reductions in HIV-infection ranging from no effect to prevention efficacy as high as 75%. As is the case with the treatment of HIV-1 infection, the ability to take the pills as prescribed, otherwise known as adherence, is a major determinant of how well the pills work. It has been proposed that with the use of long-acting agents administered in the clinic, obstacles to adherence could be overcome to some degree.
In this study GSK744 long-acting (LA) was first given to 8 rhesus macaques by injection on 2 occasions 4 weeks apart yielding drug concentrations in the blood similar to those observed in humans. One week after the first GSK744 LA injection these monkeys and 8 untreated control monkeys underwent 8 weekly intrarectal challenges with low doses of a virus related to HIV. Untreated animals were infected after an average of 2 challenges whereas no drug-treated monkeys became infected, as evidenced by the absence of detectable virus in blood and tissues as well as by the absence of an antibody response to the virus.
In a second experiment, 100% protection against virus infection was correlated with blood levels of GSK744 exceeding a particular level that is readily achievable and sustained for at least 12 to 16 weeks with an 800mg dose given by injection in humans. These preclinical studies support advancing GSK744 LA into the clinic for testing in humans as a next- generation PrEP agent.
Dr. Martin Markowitz, a co-investigator on this study and the Clinical Director at the Aaron Diamond AIDS Research Center and Aaron Diamond Professor at the Rockefeller University commented: "We are encouraged by the results of these animal studies. Perhaps most exciting is that the levels of drug that were fully protective in this animal model are readily achievable in man with quarterly (every 3 months) injections of GSK744 LA and these data form the rational for taking the agent into initial clinical studies. The Aaron Diamond AIDS Research Center will participate in a Phase 2 clinical trial of GSK744 LA in low-risk men that are set to launch in the coming months. Such a study is a necessary precursor for larger Phase 3 clinical trials in individuals at high risk of contracting HIV that will answer the question whether this long-acting drug will work to prevent HIV infection in humans."
The Aaron Diamond AIDS Research Center (ADARC) is the largest private HIV/AIDS research center in the world. Founded in 1991, it is a leader in research in HIV pathogenesis, prevention and treatment.
The Rockefeller University was this nation's first biomedical research institution. Hallmarks of the university include a research environment that provides scientists with the support they need to do imaginative science and a truly international graduate program that is unmatched for the freedom and resources it provides students to develop their capacities for innovative research.
GlaxoSmithKline a science-led global healthcare company that researches and develops a broad range of innovative medicines and brands.
ViiV Healthcare is a global specialist HIV company dedicated to delivering advances in treatment and care for people living with HIV.
The Tulane National Primate Research Center is one of eight centers that make up the National Primate Research Center Program funded by the National Institutes of Health (NIH) with primary areas of research including infectious diseases, biodefense and regenerative medicine.