Microbicides for sexually transmitted infections
Microbicides can be formulated in various delivery systems including gels, creams, lotions, aerosol sprays, tablets or films (which must be used near the time of sexual intercourse) and sponges and vaginal rings (or other devices that release the active ingredient(s) over a longer period).
[2][3][full citation needed] Detergent and surfactant microbicides such as nonoxynol-9, sodium dodecyl sulfate and Savvy (1.0% C31G), act by disrupting the viral envelope, capsid or lipid membrane of microorganisms.
Since detergent microbicides also kill host cells and impair the barrier function of healthy mucosal surfaces, they are less desirable than other agents.
[citation needed] Carrageenan preparations (such as 0.5% PRO 2000 and 3% Carraguard vaginal microbicide gels) have failed to demonstrate efficacy in preventing HIV transmission in phase III clinical multicenter trials.
PRO 2000 was demonstrated to be safe, but it did not reduce the risk of HIV infection in women (as explained in the MDP 301 trial results, released in December 2009).
[6] Similarly, the phase III efficacy trial of Carraguard showed that the drug was safe for use but ineffective in preventing HIV transmission in women.
On February 1, 2007, the International AIDS Society announced that two phase III trials of cellulose sulfate had been stopped because preliminary results suggested a potential increased risk of HIV in women who used the compound.
According to a review of microbicide drug candidates by the World Health Organization on March 16, 2007, a large number of compounds (more than 60 in early 2007) are under development;[9] at the beginning of that year, five phase III trials testing different formulations were underway.
[citation needed] It is also hoped that microbicides will block the transmission of HIV and other sexually transmitted infections, such as those caused by certain human papillomaviruses (HPV) and herpes simplex viruses (HSV).
[13] Examples of ARV drugs being tested for prevention include tenofovir, dapivirine (a diarylpyrimidine inhibitor of HIV reverse transcriptase) and UC-781.
[14] These next-generation microbicides have received attention and support because they are based on the same ARV drugs currently used to extend the survival (and improve the quality of life) of HIV-positive people.
The results of the first efficacy trial of an ARV-based microbicide, CAPRISA 004, tested 1% tenofovir in gel form to prevent male-to-female HIV transmission.
[15] Most of the first generation microbicides were formulated as semi-solid systems, such as gels, tablets, films, or creams, and were designed to be applied to the vagina before every act of intercourse.
[19] In January 2010, the National Institutes of Health awarded two grants totaling $17.5 million to the University of Pittsburgh to fund research into rectal microbicides.
In fact, long-acting formulations such as vaginal rings could provide the technology needed to deliver multiple active ingredients with different mechanisms of action.
[21] In July 2010 the Centre for the AIDS Programme of Research in South Africa (CAPRISA) released results of a study establishing proof of concept that an ARV-based, topical microbicide can reduce the likelihood of HIV transmission.
[21] The results of the CAPRISA 004 trial provide statistically significant evidence that ARVs, topically applied to the vaginal mucosa, can offer protection against HIV and (potentially) other pathogens.
In addition to demonstrating efficacy against HIV, CAPRISA 004 found evidence that tenofovir gel also prevents the transmission of herpes simplex virus type 2 (HSV-2).
[citation needed] Results released in February 2009 from a clinical trial of PRO 2000 (Indevus Pharmaceuticals), a vaginal-microbicide gel (0.5%), sparked hope that it might provide modest protection against HIV.
[22] The results of a larger trial released in December 2009 showed that PRO 2000 was safe as administered, but was ineffective in reducing the risk of HIV infection.
See Carrageenan#Medical Uses The phase III clinical trial for carrageenan-based Carraguard showed that it had no statistical effect on HIV infection, according to results released in 2008.
VOICE is evaluating three different strategies to prevent HIV in women: one ARV-based microbicide and two regimens consisting of oral ARVs on a daily basis.
It is hoped that those unable to negotiate condom use with their sexual partners would be able to reduce their risk of HIV infection with the use of an oral (or injectable) prophylactic drug.
[34] One potential risk of the PrEP approach is that drugs present in systemic circulation might, over time, create ARV-resistant HIV strains.
