Researchers To Identify, Generate Molecules For Microbicide Research

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Researchers from Case Western Reserve University in Ohio have used a technique called phagedisplay to identify and generate molecules for use in microbicide research anddevelopment, according to a study presented Monday at the 15th Conference on Retroviruses andOpportunistic Infections in Boston, the Cleveland Plain Dealer reports (McEnery, Cleveland PlainDealer, 2/5). Microbicides include a range of products -- such as gels,films and sponges -- that could help prevent the sexual transmission of HIV andother infections (Kaiser Daily HIV/AIDSReport, 12/20/07).

For the study, Michael Lederman, director of Case's Center for AIDS Research, and colleagues used phage displayto generate molecules that act like an experimental drug -- called PSC-RANTES-- that was found to block the vaginal transmission of SIV in monkeys. The drugalso could be used in the development of a microbicide for use among humans,according to the Plain Dealer. PSC-RANTES closes molecularreceptors that HIV uses to replicate, but its production is "incrediblyexpensive," according to the Plain Dealer.

Using phage display, the researchers identified and generated three moleculesthat prevented HIV from entering cells. Because the molecules occur naturallyin the body, they can be produced at a lower cost compared with PSC-RANTES, thePlain Dealer reports. The study also found that in addition tobeing antiviral agents, two of the molecules did not appear to produce anyserious immunological reactions. The researchers will present the findings at amicrobicide conference in Indialater this month and hope to attract funding for further research (Cleveland PlainDealer, 2/5).

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Antiretrovirals Linkedto Increased Risk of Heart Attack

In related news, anotherstudy presented Monday at the conference found that the antiretroviral drugsabacavir and didanosine were linked to an increased risk of heart attacks amongsome HIV-positive people, POZ reports (Horn, POZ, 2/4).

Abacavir is a second-line antiretroviral used to treat people living withHIV/AIDS who have developed resistance to first-line drugs (Kaiser Daily HIV/AIDS Report, 12/10/07).Didanosine is a generic version of Bristol-MyersSquibb's VIDEX,which was FDA-approved in December 2004. The drug is used in combination withother antiretrovirals for the treatment of HIV-1 infection (Kaiser Daily HIV/AIDS Report, 7/13/06).

For the study, the Data Collection on Adverse Events of Anti-HIV Drugs StudyGroup examined more than 33,000 HIV-positive people who have been followedduring the past seven years at clinics in Australia,Europe and North America. The researchers alsoanalyzed the risk of heart attack among those who had used or were using abacavir,didanosine and lamivudine. The researchers found that an increased risk ofheart attack was only found in participants currently receiving abacavir anddidanosine. Abacavir was associated with a 90% increased risk of heart attack,and didanosine use was associated with a 49% increased risk, the study found.An increased risk was not found among past users of the drugs. According to thestudy authors, the findings suggest that the risk of heart attack associatedwith the two drugs is reversible if use is stopped.

According to a position statement released by DAD on its Web site, the resultsneed to be interpreted carefully. The statement also stresses that the effectsof the two drugs were more pronounced among HIV-positive people withcardiovascular risk associated with other factors, according to POZ(POZ, 2/4).

Reprintedwith permission from kaisernetwork.org. You can view the entire Kaiser Daily HIV/AIDS Report, search the archives, and sign upfor email delivery at kaisernetwork.org/email . The Kaiser Daily HIV/AIDS Reportis published for kaisernetwork.org, a free service of The Henry J. KaiserFamily Foundation.

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