11 Jul, 12 | by Leslie Goode, Blogmaster
The International Partnership for Microbicides (IPM) has just announced the launch of a trial (IPM 027) to evaluate the effectiveness of the antiretroviral (ARV) drug dapivirine delivered by means of a monthly replaceable vaginal ring (http://www.ipmglobal.org/node/670). The IPM study, which has enrolled 1,650 women at four sites in South Africa, is part of a broader licensing program which also includes the Microbicides Trial Network (MTN) study ASPIRE (MTN-020) due to commence in the coming months (http://www.mtnstopshiv.org/studies/3614).
The development of an effective vaginal microbicide would be a significant new weapon in the armoury of HIV prevention – not least because, for the first time, it would place a means of protection in the hands of women, who are often most at risk from the virus. On the down side, there is the probable impact on condom use. The potential contribution of microbicides has been the object of various modelling studies: Foss & Watts (2009) predict a significant impact in contexts of low and high HIV prevalence with microbicides of even moderate efficacy (http://sti.bmj.com/content/85/4/276.abstract?sid=ec0fb4c2-06ee-4358-a8af-6e06c015bf05): while Cox and White ( 2011) argue that reductions of 30% in fifteen years could be achieved, if 49% levels of microbicide use were combined with 67% levels of male circumcision (http://sti.bmj.com/content/87/7/635.abstract?sid=ec0fb4c2-06ee-4358-a8af-6e06c015bf05). As for cost-effectiveness, Verguet & Watts give positive results for high-prevalence contexts (>2.4%) even with a low efficacy microbicide (http://sti.bmj.com/content/86/3/212.abstract?sid=ec0fb4c2-06ee-4358-a8af-6e06c015bf05).
So far, unfortunately, the microbicides have not come up with the goods. Some 23 products are currently in the course of development. Microbicides act in different ways – some by creating a physical barrier, such as PRO2000, a trial of which is discussed by Kamali & Lacey (2009) (http://sti.bmj.com/content/86/3/222.abstract?sid=ec0fb4c2-06ee-4358-a8af-6e06c015bf05): others by enhancing vaginal defence mechanisms or by disabling the pathogens. Trials of these microbicides having proved unsuccessful, the most promising candidates now seem to be ARV drugs which prevent replication of the virus inside the cell. Amongst the latter are Tenofovir gel, unsuccessfully trialled by the MTN VOICE trial (MTN 003), and now, most recently, the dapivirine ring, soon to be tested by IPM 027 and MTN ASPIRE (http://www.mtnstopshiv.org/node/82).
Both of the trials recently announced (IPM 027 and MTN 020) are phase III trials at the cutting edge of microbicide research.