In trials, GSK744 totally protects monkeys against simian HIV

by Mike Andrew - SGN Staff Writer

A new PrEP drug offers monkeys 100% protection against HIV-like viruses, a paper presented this week at the Conference on Retroviruses and Opportunistic Infections (CROI) says.

The injectable integrase inhibitor GSK744 was tested on rhesus macaques, and was found to have a half-life of 21 to 50 days. According to researchers, it remained in the monkeys in amounts sufficient to suppress 90% of HIV replication for six months, and more than four times that level for four months.

In other words, if it proves to be as effective in humans, the drug could be administered as a quarterly injection, as part of a routine medical check-up and prevent HIV infections. HIV-negative human volunteers have already been given single doses of the drug, the research paper revealed.

STRIKING RESULTS
Scientists at the Aaron Diamond AIDS Research Center injected GSK744 into eight male macaques and then a week later started "challenging" their health by introducing SHIV, or simian HIV, a version of HIV engineered to infect monkeys. Doses of SHIV were administered rectally, to simulate anal sex.

At the same time they administered SHIV to eight control monkeys without giving them GSK744 first. All the control monkeys not given GSK744 became infected, on average after two "challenges," though one reportedly took seven "challenges" before becoming infected.

In contrast, none of the monkeys given GSK744 became infected or have shown any sign of virus in their blood up to three weeks after the last dose of SHIV.

Levels of GSK744 seen in the test monkeys' rectal tissues were equivalent to a level that would be expected to be protective in humans, and it stayed more than four times above the minimum effectiveness level for the full eight weeks of viral "challenge" in six monkeys.

In the other two monkeys, it fell below the four-times minimum level at week seven - in other words, just before the last viral "challenge."

PREVENTION MADE EASIER
GSK744 is similar to the drug dolutegravir, which is already nearing approval as an anti-HIV drug in Europe and the U.S. The drug's manufacturer, GlaxoSmithKline, has been able to formulate it as a nanoparticle suspension - tiny 'packets' of the drug floating in fluid, which provide a long-lasting supply of the drug when injected.

Since adherence is turning out to be a major barrier to the effectiveness of pre-exposure prophylaxis - or PrEP drugs - medications that can be given quarterly as part of ordinary check-ups could be a more feasible way of offering protection against HIV infections.

In a separate monkey study, researchers from the CDC protected female monkeys using another long-lasting PrEP method - a ring impregnated with tenofovir that could be inserted into the vagina.

In this case, they used a polyurethane ring that was replaced every four weeks over a 16-week period. Six monkeys exposed to SHIV were protected against infection, whereas 11 out of 12 not given the ring became infected. Unlike the injectable formulation, human research into vaginal rings is already well-advanced, with several studies already ongoing. But this is the first time it has been shown that a ring can deliver enough of the widely used drug tenofovir to completely protect monkeys, researchers said, and is the first time a ring has been demonstrated to protect monkeys who are repeatedly "challenged" with SHIV.

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