March 4, 2009

experts comment on SIV microbicide research to be published in Nature

The research shows that a common chemical, when applied in gel form, can prevent the sread of SIV, the equivalent of HIV in monkeys.

Prof Andrew McMichael, Director of Weatherall Institute of Molecular Medicine, University of Oxford, said:

“This is a very exciting report that shows that a local application of simple chemical compound can prevent infection of the genital tract by SIV, the monkey version of HIV. The experiments start with an analysis of how SIV infection gets started in genital tissues demonstrating a role for a locally produced chemokine (cellular hormone) that attracts in the main target cells for SIV, the CD4 T cells, to the genital tract. They show that glycerol monolaurate inhibits production of this chemokine. They then demonstrate that the same compound prevents infection of SIV when the virus is inoculated into the vagina of monkeys. The protective effect is dramatic.

“This is an inexpensive compound that could be used in humans and clinical trials are very likely to follow. A complicating factor might be the presence of other genital tract infections which are known to increase susceptibility to infection by other means so a clinical trial should in my view include treatment of such infections.

“The finding demonstrates how critically important studies in monkeys are to the understanding of HIV infection and development of strategies to prevent infection. Current proposals to restrict non-human primate research in the EU could prevent this type of work which could have outcomes of immense benefit to human health.”

Dr Adriano Boasso, Research Fellow, Imperial College London, said:

“The study published in today’s issue of Nature uses the animal model of SIV infection in rhesus macaques and provides encouraging results on the possibility of preventing HIV infection through the vaginal route, by applying topic compounds which modulate the immune response rather than directly block the virus.

“When a virus encounters the organism at mucosal level, a series of inflammatory processes and immune reactions are activated at the site of infection. These immune mechanisms have developed to protect us from infections, but HIV (and SIV) exploits the inflammation and the rapid immune response that occurs in the vaginal mucosa to favour its own spread to the rest of the organism, as demonstrated by the authors.

“When a vaginal cream containing a compound with anti-inflammatory properties (glycerol monolaurate, GML) was applied in five animals both before and repeatedly after the challenge with SIV, this cascade of immunologic and inflammatory events was blocked and the infection was prevented.

“The idea that an excessive activation of the immune system favours HIV infection and disease progression is very well accepted. Attempts to block some of these immune mechanisms have already been considered as potential therapeutic approaches. This study suggests that topic interventions that limit inflammation may be used very early during the infection, directly at the site where the virus first strikes, to prevent its spread.

“The results of this study are undoubtedly very encouraging, but a call for caution is still necessary when we consider that this treatment was tested on a relatively small number of animals and that several years of research are still needed to determine whether this approach will eventually develop into a prospective preventive drug.”