Researchers Use Technique to Identify, Generate Molecules for Microbicide Research, Development

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

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

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

Antiretrovirals Linked to Increased Risk of Heart Attack
In related news, another study presented Monday at the conference found that the antiretroviral drugs abacavir and didanosine were linked to an increased risk of heart attacks among some HIV-positive people, POZ reports (Horn, POZ, 2/4).

Abacavir is a second-line antiretroviral used to treat people living with HIV/AIDS who have developed resistance to first-line drugs (Kaiser Daily HIV/AIDS Report, 12/10/07). Didanosine is a generic version of Bristol-Myers Squibb's VIDEX, which was FDA-approved in December 2004. The drug is used in combination with other 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 Study Group examined more than 33,000 HIV-positive people who have been followed during the past seven years at clinics in Australia, Europe and North America. The researchers also analyzed the risk of heart attack among those who had used or were using abacavir, didanosine and lamivudine. The researchers found that an increased risk of heart attack was only found in participants currently receiving abacavir and didanosine. 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 the study authors, the findings suggest that the risk of heart attack associated with the two drugs is reversible if use is stopped.

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

DAD's position statement is available online (.pdf).

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