EFFICACY OF AIDS DRUGS EBBING

By Raja Mishra

Boston Globe 19 Dec. 2001

The vast majority of HIV patients in the United States carry a form of the disease able to resist one or more anti-AIDS drugs, according to research released yesterday, suggesting to alarmed doctors that the epidemic might soon take a deadly turn.

The advent of powerful anti-AIDS drugs a decade ago triggered a revolution in HIV care, restoring health to thousands of once-doomed patients. But doctors realized it was borrowed time: The resilient virus would eventually evolve defenses against medicines. Yesterday's study, the first national review of HIV resistance to drugs, found resistance is building more rapidly than expected.

"We could be right back where we were in 1984, when the virus was unstoppable," said Larry Kessler, executive director of the AIDS Action Committee, a Boston nonprofit.

Seventy-eight percent of HIV patients tracked by the study developed resistance to at least one of the 15 anti-AIDS drugs available. Many strains were even more elusive: 42 percent were unaffected by all protease inhibitors, the best-known family of anti-AIDS drugs.

"This is something that we really have been worrying about, dreading," Kessler said, adding that he had assumed, based on smaller previous studies, that one in four HIV cases was resistant rather than three in four, as yesterday's study indicated.

HIV patients typically take combinations of anti-AIDS drugs - "cocktails" - that attack the virus from numerous angles. A single drug is no match for HIV's evolutionary skills, which allow it to quickly mutate.

When signs of resistance appear, doctors switch to other combinations. But yesterday's news left some doctors and patients worried that a new generation of patients might not have such a luxury. It also suggests that older patients, who have cycled through many drugs, are running out of time.

"If I should happen to fail the cocktail I'm taking, I don't know where to go," said Charles Lacombe, 53, of Boston, whose HIV is resistant to most anti-AIDS drugs.

Lacombe, diagnosed with HIV in 1992, marvels that he has lived so long thanks to anti-AIDS drugs. He is one of thousands of such patients who might one day soon be faced with severe illness again.

In 1995, he began taking three drugs, including the protease inhibitor crixivan and the much-used drug AZT. But the side effects - pancreas damage, kidney stones, bulging fatty deposits - were so severe that his doctor put him on new drugs.

"My doctor said, 'I don't want to lose you to side effects,"' Lacombe said.

Almost immediately after the first drug combination was cut off, however, the virus within him became resistant to all protease inhibitors, AZT, and a third class of drugs. His current regimen might be the last effective combination, he said.

The threat of drug resistance has been a staple of anti-AIDS education for years, but Lacombe said many of the gay men - a high-risk group - that he socializes with continue to believe anti-AIDS drugs offer lifetime protection.

"People are back to the same old practices that started this epidemic anyway," he said, referring to unprotected sexual intercourse.

Dr. Ronald Valdiserri, deputy chief of sexually transmitted diseases for the federal Centers for Disease Control and Prevention, had similar concerns, saying the new study "underscores the importance of prevention" of infections in the first place.

The study followed 209,000 HIV-infected US adults and was presented yesterday at an American Society of Microbiology conference in Chicago devoted to drug resistance issues. It also found that:

Those receiving the best HIV care, with comprehensive access to drugs, had the highest levels of resistance.

The oldest family of anti-HIV drugs, reverse transcriptase inhibitors, has become the least effective, with 70 percent of patients resistant.

Drug resistance was less prevalent among the patients of experienced AIDS doctors with high caseloads.

That last finding suggested hope to some researchers.

"The bad news here is that HIV is a highly adaptable virus that can outsmart the drugs we now have available," said Dr. Douglas Richman, the new study's author and a professor at the University of California at San Diego. "The good news is that there are approaches physicians and patients can employ to limit the impact of resistance and maintain viral suppression."