Tenth of H.I.V. Cases in a Study in Europe Are Resistant to Drugs

The biggest study, so far, of resistance to AIDS drugs, to be released today at an international AIDS conference in Paris, finds that about 10 percent of all newly infected patients in Europe are infected with drug-resistant strains.

The biggest study, so far, of resistance to AIDS drugs, to be released today at an international AIDS conference in Paris, finds that about 10 percent of all newly infected patients in Europe are infected with drug-resistant strains.The researcher who led the study called the level of resistance to some anti-AIDS drugs “surprisingly high.” Other scientists at the conference agreed that the findings had worldwide public health implications and made the hunt for new classes of AIDS drugs even more critical. They said the figure suggested that many AIDS patients who are in treatment go back to engaging in high-risk sex or needle-sharing. It also suggested that an “order of battle” approach to prescribing AIDS drugs, like that used for tuberculosis medicines, should be adopted in place of the current free-for-all.For example, one researcher said, a drug like nevirapine, which can prevent mother-child transmission with just one dose, might be restricted to that use only, so resistance to it cannot grow as it would if thousands of patients were put on it for life. Also, public health authorities could tell doctors which drug combinations to prescribe first, second and third as resistance was encountered.Smaller tests to measure resistance have been done in San Francisco, in a group of nine other American cities and in Switzerland. While some of those studies found higher levels of resistance of 225 patients in San Francisco, 27 percent were drug resistant the new study is thought to be the first to give a reliable measure of the phenomenon across a broader population, said Dr. Charles Boucher, the virology professor at Utrecht University who led the new study.”You’re not talking about high-risk inner city San Francisco,” he said. “This is across Europe.”Some doctors said the study suggested that all new AIDS patients should be tested to determine the drug resistance of the strains infecting them.Those tests can cost between $200 and $800 each and take between a week and a month to complete, factors that could greatly raise the price of plans to bring inexpensive AIDS drugs to poor countries. For example, the Bush administration has promised to spend $15 billion bringing such drugs to Africa and the Caribbean.But experts emphasized that the possibility of creating drug-resistant strains of the virus that causes AIDS was not a reason to deny drugs to the poor.Dr. Robert M. Grant, a professor of medicine at the University of California at San Francisco, who led the San Francisco study, said that doing so would be unethical. Dr. Boucher said it would also be medically unwise, since the drugs drive down virus levels, making transmission less likely.Other experts said that the findings underscored the need for better guidelines on the medicines’ use as the treatment effort gears up. “It means we have to be smart about how we use the drugs to avoid as much resistance as we can,” said Dr. Scott M. Hammer, chief of infectious disease at Columbia-Presbyterian Medical Center in New York, who attended the International AIDS Society conference in Paris this week and saw an early copy of the study.The study tested 1,633 patients from 17 European countries who had just been diagnosed with the virus that causes AIDS and who had not yet been treated for it. (It is nicknamed the Catch study for “combined analysis of resistance transmission over time of chronically and acute infected H.I.V. patients in Europe.”)About 9.6 percent of the patients were resistant to at least one of the three types of anti-retroviral drugs that suppress the virus that causes AIDS.There are 17 such drugs, but they fall into three classes: nucleoside reverse-transcriptase inhibitors, non-nucleoside reverse-transcriptase inhibitors and protease inhibitors. Normally, a patient takes a “triple therapy cocktail” of all three to attack the virus at three different sites.Resistance to the first group was found in 6.9 percent of those studied, resistance to the second in 2.6 percent and resistance to protease inhibitors in 2.2 percent.Two new classes of drugs, fusion inhibitors and integrase inhibitors, are still in testing stages, so resistance to them is presumed not to exist yet.Drug-resistant strains appear because the virus mutates rapidly and they thrive when patients take their drugs carelessly. For patients to be newly infected with resistant strains, they must have been infected by people with H.I.V. who had gone back to high-risk behavior despite having caught a disease that is usually fatal.No large study of drug resistance has been done in Africa. It is too early, Dr. Boucher said, because so few Africans are getting treatment.In sub-Saharan Africa, where 2.4 million people died of AIDS in 2002, only about 50,000 are getting anti-retroviral drugs, according to the United Nations.For that reason, argued Dr. Roy M. Gulick, a professor at Cornell University’s Weill Medical College, there is probably little point in doing expensive tests for resistance in Africa now.”The risk of resistance in most African populations right now is very low or zero,” he said.That likelihood was borne out by another result in the Catch study. Resistance was much higher, at 11.3 percent, among Europeans who had subtype B of the virus that causes AIDS, compared to those with non-B subtypes, in whom it was 3.3 percent.Subtype B infects 98 percent of Americans and about 60 percent of Europeans. It is the subtype that has spread most widely since AIDS was discovered in Los Angeles, San Francisco and New York in the early 1980’s. Though subtype B originally came from central Africa, subtypes A, C and so on prevail in other parts of Africa and in Asia. Researchers believe Europe has a broader mix than the United States because more Africans and Asians immigrate there from former colonies.But the growth of resistance “is a fact of life,” said Dr. Joep Lange, a professor of internal medicine at the University of Amsterdam and president of the International AIDS Society. “It happens with antibiotics; it happens with TB. If you use drugs, you’ll eventually see resistant strains.”Therefore, he and other researchers said, when the drugs come to Africa, they must be handed out carefully, with laboratories, doctors and epidemiologists monitoring patients and community resistance.Dr. Gulick said the study also showed that prevention efforts in wealthy countries needed to be focused not just on uninfected young people, but on infected ones, “to tell them, `You have the infection but you shouldn’t spread it to other people,’ ” he said.(Source: The New York Times, 16 July 2003, By DONALD G. McNEIL Jr.)