HIV Drug Resistance Exceeds Previous Estimates

"The high proportion is surprising," said study leader Douglas D. Richman, M.D., an infectious diseases specialist who directs the Research Center for AIDS and HIV Infection at the Department of Veterans Affairs' (VA) San Diego Health Care System and the Center for AIDS Research at the University of California, San Diego (UCSD). He said earlier research on HIV drug resistance focused only on smaller groups of patients.

Samuel A. Bozette, M.D., Ph.D., a co-leader of the study, added: "Many of the previous studies were relatively small and in highly selected populations, so that accurate estimates were not possible. What's important here is that we could obtain a national prevalence that considers all types of adult patients across all types of practices."

The researchers tested blood plasma samples taken in 1999 from 1,647 men and women enrolled in the HIV Cost and Service Utilization Study. Dr. Richman and colleagues used in their study the ViroLogic PhenoSense HIV Drug Resistance Assay, and found that 78 percent of patients showed signs of resistance to one or more drugs typically used to treat HIV.

Drug resistance was particularly high--87 percent--among those who at the time of testing were receiving antiretroviral therapy, often consisting of potent "cocktails" of three or more drugs. Among those who had received antiretroviral therapy but stopped before testing, 41 percent carried drug-resistant mutations of HIV.

While drug resistance is more common in those receiving treatment, drug-resistant mutant strains of HIV can be transmitted through sexual contact and other means. Other studies by Dr. Richman's group show that up to 20 percent of newly diagnosed HIV patients have a resistant form of the virus--even before they themselves start antiviral therapy.

"We need to step up efforts to prevent transmission of drug-resistant virus, as this appears to be an increasing problem," said Dr. Richman.

In the study, demographic factors linked with better access to HIV treatment were correlated with increased drug resistance. Most at risk were non-Hispanic white males, men having sex with other men, and those with higher education and private medical insurance. Broken down by drug type, the highest rate of resistance--70 percent--was to the class of drugs called nucleoside reverse transcriptase inhibitors, which are almost always a part of antiviral treatment. However according to Dr. Richman, "Resistance was frequent to all classes of drugs used against HIV."

The findings, added Dr. Richman, stress the importance of drug resistance testing, which can identify which drugs will not be effective for a patient. This has in fact become the standard of care, and is paid for by many states, including California, and VA's Veterans Health Administration, which runs the nation's largest healthcare system.

"We need more knowledgeable and effective use of drugs by patients and caretakers," said Dr. Richman. "There needs to be more use of drug resistance testing to manage patients who have failed treatment and who have been recently infected. These tests help select drugs that are more likely to work, and to avoid drugs that will no longer work." At the same time, he said, "We need new drugs that are effective against drug-resistant virus."

The HIV Cost and Service Utilization Study involved a broad consortium of institutions, including the Agency for Healthcare Quality and Research; the Health Resources and Services Administration; the National Institutes of Health; and RAND, where the research is based.

Leading the effort are Martin Shapiro, M.D., of the University of California, Los Angeles; and Dr. Bozzette, of the VA San Diego Health Care System, UCSD and RAND Health. The study is intended to collect data on a nationally representative sample of people receiving care for HIV infection.

Collaborating on Dr. Richman's study were co-leader Samuel A. Bozzette, M.D., Ph.D., Nicholas Hellmann, M.D., Terri Wrin, and Keith Dawson, M.S., of ViroLogic, Inc.; and Sally Morton, Ph.D., and Sandy Chien, M.S., of RAND. Support was provided through the HIV Cost and Service Utilization Study, and Quest Diagnostics and ViroLogic.