Science: Long-Acting Drug Protects Monkeys Against SHIV

A potent drug to prevent HIV infection, now in clinical trials, has been reformulated into a long-acting injectable drug that can protect macaque monkeys from the simian/human immunodeficiency virus (SHIV) for more than two months at a time.

SHIV is a hybird virus that combines parts of the simian and human immunodeficiency virus genomes, created by researchers as a useful test virus for studying HIV infections. The efficacy and safety of the injectable drug have yet not been tested in humans. But, researchers hope that someday it could be offered as a monthly or even quarterly injection that would protect people at high risk for contracting HIV.

The GSK744 integrase inhibitor could prevent HIV infection by disrupting the virus before it inserts itself into human chromosomes. | G. Grullón/Science

The macaque tests of the drug by Chasity Andrews and David Ho at Rockefeller University and colleagues are reported in the 7 March issue of the journal Science. (The article is freely available with registration at www.sciencemag.org).

"This is the most exciting thing happening that I know of in HIV prevention studies today," said Robert Grant, a virologist at the University of California, San Francisco, who was not involved in the studies. Grant was interviewed in a related Science news story by Jon Cohen.

A long-acting drug that could protect against HIV for months at a time would be a significant step forward in pre-exposure prophylaxis (PrEP) treatments, which are antiretroviral drugs taken by people who are not infected with HIV but are at high risk of infection. PrEP treatment in pill form was approved by the U.S. Food and Drug Administration in 2012, but the treatment only works as HIV prevention if people take their pills every day.

Many people have difficulty adhering to this daily schedule, and non-adherence significantly lowers the effectiveness of PrEP at preventing HIV infection, Andrews said at a 4 March press conference at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts.

The experimental injectable drug, under development by GlaxoSmithKline, is called GSK744 LA. It works by inhibiting an enzyme that HIV and SHIV use to integrate into chromosomes and make copies of themselves. Andrews and colleagues tested its effectiveness in monkeys that were infected repeatedly in the rectum with SHIV.

When one dose of the drug was given to monkeys one week before these infection challenges, they protected the monkeys against weekly SHIV challenges for slightly more than two months. As concentrations of the drug declined over time in the monkeys, their risk of infection increased, the researchers noted.

Ho and colleagues say that a similar dose might offer a longer period of protection against HIV in humans, perhaps up to three months.

At the CROI conference, Andrews said the research team is also testing the effectiveness of GSK744 LA in macaques that are infected vaginally with the virus. Although the testing is far from complete, she said the injectable drug has showed promise in protecting against vaginal SHIV infections as well.