Rockefeller And Aaron Diamond Researchers Say Resistance To HIV Drugs May Be Higher Than Previously Thought

A study of patients infected with the AIDS virus revealed that about one in six was carrying a strain that is resistant to at least one of the drugs targeting HIV, researchers report from the Aaron Diamond AIDS Research Center, an affiliate of The Rockefeller University. Lead author Daniel Boden, M.D., and 11 colleagues report the research as the cover story in the Sept. 22-29 issue of the Journal of the American Medical Association. The authors suggest that further research should try to establish whether AIDS therapy structured around HIV-resistance testing would be more effective than current methods.

Although the researchers caution that the analysis was limited to a subset of the AIDS population -- mostly gay, white men who were recently infected -- the percentage of patients in the group carrying a resistant strain was significant. The researchers found that viruses resistant to more than one drug were much less common.

"There are two important messages we should draw from this study," Boden says. "First, that we need to explore how widespread this resistance is. Is the percentage going to be the same in the AIDS population in general? Is it affected at all by means of transmission? The second message is that HIV has a much tougher time resisting three drugs than one. Until we know how much resistance there is and what is causing it, we recommend that infected patients who are able to should follow the multidrug therapy."

The study is the first to be published that attempts to measure the prevalence of transmitted drug-resistant HIV-1 in the United States during the era of combination anti-retroviral therapy. Since it was implemented four years ago, the multidrug approach -- in which infected patients take a combination of drugs (usually three) every day -- has caused a marked reduction in AIDS cases and AIDS deaths. For example, the death rate from AIDS dropped 47 percent in the United States between 1996 and 1997. Scientists have been concerned, however, that the success of antiretroviral drugs has resulted in the increased transmission of drug-resistant strains of the virus.

To measure the prevalence of this resistance, the researchers performed genetic analysis on virus in blood drawn from 80 patients to find any HIV mutations associated with drug resistance. They found that 13 of the patients, or 16.3 percent of the total, carried strains that were less susceptible to an antiretroviral drug by a factor of three or more. The scientists said the actual percentage of patients carrying resistant strains in the group is probably higher because other mutations that confer resistance have not yet been identified. Viruses resistant to more than one drug were found in only 3 patients, constituting 3.8 percent of the total.

"Rather than jumping to any conclusions about whether resistant strains of HIV are being widely spread, we need to measure the resistance in other populations," says study co-author Martin Markowitz, M.D. "If it appears that HIV resistance to drugs is becoming more common in the future, we may have to alter current strategies for treatment. But until we know more, we do not want patients to stop taking drugs because in most cases they are quite effective." The scientists recommend initiation of clinical trials to determine whether therapy guided by resistance testing would work better than issuing the standard drug or combination of drugs. Such testing might lead to drug therapies tailored around the specific resistant HIV strain found in a particular patient.

Boden's and Markowitz's co-authors are Arlene Hurley, R.N., Linqi Zhang, Ph.D., Yunzhen Cao, M.D., Yong Guo, M.S. Elizabeth Jones, B.A., John Tsay, B.A., James Ip, B.A., of the Aaron Diamond Aids Research Center at Rockefeller University, Charles Farthing, M.D., of AIDS Healthcare Foundation, and Kay Limoli, M.S., and Neil Parkin, Ph.D., of ViroLogic, Inc. This research was supported in part by the National Institute of Allergy and Infectious Diseases, part of the federal government's National Institutes of Health and by a General Clinical Research Center grant (M01-RR00102) from the National Center for Research Resources at NIH.

Rockefeller began in 1901 as The Rockefeller Institute for Medical Research, the first U.S. biomedical research center. Rockefeller faculty members have made significant achievements, including the discovery that DNA is the carrier of genetic information and the launching of the scientific field of modern cell biology. The university has ties to 19 Nobel laureates. Thirty-three faculty members are elected members of the U.S. National Academy of Sciences, including the president, Arnold J. Levine, Ph.D.

The Aaron Diamond AIDS Research Center was established in 1991 to focus on the basic science of AIDS and HIV in a research environment conducive to the highest level of scientific creativity. In June 1996, the Research Center affiliated with Rockefeller University.