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Monthly injectable drug offers 100% protection against HIV in monkeys – could be dosed every three months
Gus Cairns, 2013-03-04 16:50:00
An injectable, long-lasting integrase inhibitor drug, when given to rhesus macaques exposed to a monkey-adapted version of HIV, completely protected them against the virus. This drug, an injectable version of GSK1265744 (GSK744), has already been given as a single dose to HIV-negative human volunteers, and has a half-life of 21 to 50 days. Levels stayed above the IC90 (the level necessary to suppress 90% of HIV replication) for six months, and above four times this level for four months.
This means that if it proves safe and effective in humans, it could be given as an injection as little as four times a year, though individual variations seen in this study mean that monthly dosing may be safer.
GSK744 is similar to dolutegravir, which is already nearing approval as an anti-HIV drug in Europe and the US. It is effective against HIV, though, at lower concentrations in the body, which means manufacturers GlaxoSmithKline have 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.
Scientists at the Aaron Diamond AIDS Research Institute injected GSK744 into eight male macaques and then a week later started 'challenging' them by introducing SHIV, a monkey adapted version of HIV as weekly doses (eight in total) in the rectum, to simulate anal sex. At the same time they challenged eight control monkeys without giving them GSK744 first. The monkeys on GSK744 were given a second dose four weeks after the first.
All the monkeys not given GSK744 became infected, on average after two challenges, though one took seven challenges. 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 challenge.
Levels of GSK744 seen in these monkeys’ rectal tissues were equivalent to a level that would be expected to be protective in humans, and stayed above the four-times-IC90 level for the full eight weeks of viral challenge in six monkeys. In the other two levels, it fell below the four-times IC90 level at week seven, in other words, just before the last viral challenge .
Given that adherence is turning out to be a major barrier to the effectiveness of pre-exposure prophylaxis – see this report and this one on the VOICE trial – HIV drugs that can be given by injection at quarterly sexual health check-ups could, in the long term, be a more feasible way of offering biomedical protection against HIV. The researchers are studying the protected monkeys to see if there is any sign of virus in their systems and to determine the minimum effective dose.
Source:1
