Breaking the Drug Drought

At one of the last major AIDS conferences of 2008 (the Interscience Conference on Antimicrobial Agents and Chemotherapy) researchers indicated that the end for what many have characterized as a dry spell in anti-HIV drug development may finally be on the horizon, with promising data on three new medications. ''Bevirimat. Although researchers had struggled with liquid versus tablet formulations of this maturation inhibitor and initially had difficulty achieving formulations with therapeutic drug levels, the kinks were finally worked out and data from a Phase II human trial were presented. They showed that bevirimat lowered viral loads by a 1.2-log drop after just two weeks of treatment. And more good news: Reported side effects were the same as those associated with use of a placebo. Final Phase III clinical trials are coming. ''Elvucitabine. This new nucleoside analog is similar to Epivir (3TC) but has demonstrated activity against HIV that has developed a major genetic mutation conveying resistance to 3TC. Elvucitabine appears to be more potent than 3TC in treating hepatitis B as well. A small study comparing elvucitabine and 3TC in combination with Viread and Sustiva showed that the new medication performed slightly less well, but researchers say that was likely due to the unexplained dropout of some participants in the elvucitabine arm. Side effects were not the cause. Studies are ongoing. ''RDEA-806. Although researchers are still grappling with formulation problems with this new nonnucleoside reverse transcriptase inhibitors, the medication has been shown to be effective against HIV with K103N mutations that convey resistance to most other nonnuke meds. Data from a Phase IIa trial showed that RDEA-806 produced a 1.8-log drop in viral levels after seven days of treatment, and there were no reports of the central nervous system side effects or rash linked with other NNRTIs. The developers say they believe it may take multiple viral genetic mutations for HIV to develop resistance against RDEA-806. Phase IIb clinical trials are about to start. Researchers at the conference also presented data from the North American AIDS Cohort Collaboration on Research and Design study, which showed that delaying the initiation of HIV treatment until CD4-cell counts were below 350 worsened morbidity and mortality statistics. Earlier initiation of anti-HIV therapy should provide for better rises in CD4-cell counts, more successful viral suppression, and a reduced risk of cardiac, liver, and renal disease as well as non-HIV related cancer, according to the study. U.S. and U.K. treatment guidelines as well as those of the International AIDS Society already call for the initiation of antiretroviral therapy when CD4-cell counts are above 350 on a case-by-case basis. In my next column I'll discuss more reports from the conference, including some impressive studies that used the latest technology to explore the possibility of eradicating HIV reservoirs and the release of data on new, highly sensitive resistance assays. Stay tuned for what is shaping up to be a good year for treatment. Bowers is an HIV specialist and is board-certified in family medicine. He is in private practice in New York City. Learn more about Bowers at https://www.danbowersmd.com