A study presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston has found that a single dose of a microbicide gel containing the integrase inhibitor raltegravir (Isentress), given three hours after vaginal exposure to HIV, protected five out of six monkeys against HIV infection.
Charles Dobard of the US Centers for Disease Control (CDC) told the conference that, after conducting a number of animal studies of pre-exposure oral and microbicide gel prophylaxis with tenofovir and other drugs, which led to trials being conducted in humans, they wanted to see if using a microbicide gel after sexual exposure might prevent infection too. This, Dobard said, could potentially be a strategy even more friendly to women than a microbicide used before sex.
The CDC team first conducted test-tube experiments to find out how long after exposure to HIV topically applied drugs could be applied and still have an effect. They found that reverse transcriptase inhibitors such as tenofovir began to lose efficacy (less than 90% viral inhibition) if applied more than two hours after exposure. In contrast integrase inhibitors could be applied up to ten hours after exposure before losing efficacy.
Accordingly the research team made up a microbicide gel using 1% raltegravir and the carrier gel hydroxyethylcellulose (HEC), a neutral substance used as placebo in microbicide trials.
Ten monkeys were challenged twice a week for ten weeks (20 exposures) by vaginal introduction of a combination monkey/human HIV virus (SHIV) designed to mimic the course of HIV infection in monkeys. Six out of the ten monkeys were then given a dose of three millilitres of raltegravir gel, three hours after exposure while the other four received HEC gel alone.
All four animals not given raltegravir became infected, three of them after ten exposures. In contrast only one of the six animals given raltegravir became infected.
No drug resistance was seen in the one monkey that did become infected, and its viral load was the same as control animals. However the levels of SHIV found in vaginal fluid was 30 to 100 times lower in the monkey infected on raltegravir gel compared with the control animals, at least during the acute period when viral load is high.
“This is the first evidence finding efficacy for a post-exposure topical gel,” Charles Dobard said.
You can view the abstract from this research on the official conference website:
Abstract 30: www.retroconference.org/2011/Abstracts/41607.htm
You can also watch webcasts of presentations made at the conference.
The webcast from the conference session HIV Prevention: HSV2, Topical and Oral PrEP, and Circumcision, includes the speaker Charles Dobard.
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Dobard C et al. High protection against vaginal infection in macaques by PEP with gel containing RAL. 18th Conference on Retroviruses and Opportunistic Infections, Boston, abstract 30, 2011.
