New Drug Shows Anti-Viral Benefit Against HIV but Produces Renal Side Effects
For immediate release: December 21, 1999
Boston, MA and San Francisco, CA--An experimental drug that fights the AIDS virus by attacking the enzymes that enable it to replicate has proved effective in a nationwide clinical study.
Named adefovir dipivoxil, the drug reduced viral load--the amount of HIV in the blood--by an average of about 60 percent in patients. Adefovir is an antiretroviral drug known as a nucleotide analog.
The drug was tested in a double-blind trial involving 442 HIV-positive patients at 33 U.S. HIV treatment centers. The study was designed to test the ability of adefovir to produce an effect and its safety.
Study findings are reported in the December 22 issue of the Journal of the American Medical Association. Lead authors are James Kahn, MD, associate professor of medicine at the University of California, San Francisco, and Stephen Lagakos, PhD, chair of the Department of Biostatistics at the Harvard School of Public Health.
Adefovir was developed by Gilead Sciences, Inc., of Foster City, California, which sponsored the study. Last month, an advisory panel of the Food and Drug Administration recommended against approval of Gilead's application for the drug. The company has since announced that it will terminate U.S. development of adefovir. An accompanying editorial in JAMA reviews the development of drugs that are effective against drug-resistant HIV and cites the FDA decision.
"We found adefovir to show promise as an HIV medication, particularly in patients whose virus showed resistance to other nucleotide analogs," said Kahn. "Its benefits must be balanced, however, with side effects that were manageable but did involve nausea and other gastro-intestinal problems as well as increasing kidney problems in about 60 percent of the patients over time." Kahn specializes in treating HIV/AIDS patients at the UCSF Positive Health Program based at San Francisco General Hospital Medical Center.
Among other positive results, the drug showed that it remained active when integrated with other antiretroviral drugs in a treatment regimen known as combination therapy. Combination therapy is designed to maximum the medication potency against HIV by striking at a variety of different biochemical mechanisms and at several vulnerable points in the viral lifecycle.
Over the past four years, antiretroviral therapy has led to improved survival for many HIV patients, however, because of the development of resistance, there is an ongoing effort to develop new anti-HIV medications that will add to the drug arsenal for combination therapy, Kahn said. "Every patient is different, so there is no universal combination drug therapy. The combination needs to be adjusted and individually tailored for each patient for optimum benefit. Although adefovir had significant kidney-related toxicities, it is still a shame that another treatment option is not going to be available to our patients," said Kahn.
Like other nucleotide analogs, adefovir works by inhibiting a critical enzyme called reverse transcriptase (RT). Current experience in treating HIV patients shows that the best results occur when combination therapy involves drugs that are RT inhibitors--such as adefovir--along with protease inhibitors or other classes of drugs. The goal of combination therapy is to keep HIV from replicating and then spreading into more cells and to give the body the chance to increase its supply of the infection-fighting CD4+ cells that are destroyed by the virus.
For complete text of the article, please visit: http://jama.ama-assn.org/cgi/content/abstract/282/24/2305
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