Cocktail Hangover / Drug-resistant HIV on rise as medicines misused

PUBLICATION: Newsday
BY: Laurie Garrett. STAFF WRITER
EDITION: NASSAU AND
SECTION: News
DATE: 12-18-2001
A12

Widespread misuse of anti-HIV drugs has led to drug resistance in at
least half the population under treatment for the disease in the United
States, scientists are reporting today.

Most striking, researchers said, is the demographic breakdown of drug
resistance. Contrary to forecasts made in 1996 when combination drug
therapy was introduced, it is not the poor and IV drug users who have
the highest rates of resistance because of failure to properly take the
drugs. Rather, it is white, gay, fully insured, highly educated men who
carry the most highly drug-resistant viruses.

A national survey, conducted by RAND Corp. of Santa Monica and the
University of California in San Diego of some 2,000 HIV patients, found
that 64 percent are now getting less benefit from their drug cocktails
than they were two or three years ago, as measured by rising levels of
viruses in their bloodstreams. The purpose of Highly Active
Antiretroviral Therapy, or HAART, is to lower the numbers of viruses in
a patient's blood to below the limits of laboratory detection. Once
viruses get past the HAART defense and surge into the bloodstream,
patients have to switch to different drug combinations to keep virus
levels low.

Since HAART was introduced in 1996, many patients - most, according to
the new study - have switched so many times, they now receive less than
optimal benefits from any anti-HIV combinations.

Among those who have such rising HIV blood levels, 78 percent have
drug-resistant HIV. Even newly infected individuals, who have not taken
the treatment cocktails, are showing astonishing levels of drug
resistance - one out of five carry resistant viruses, acquired from
their sexual or drug-use partners.

This means that by the most conservative possible reckoning of the data,
"half of the people under care in the United States right now have
resistant virus. It's quite frightening," senior researcher Dr. Doug
Richman of UCSD said in an interview. Richman will present the findings
today at the annual Interscience Conference on Antibacterial Agents and
Chemotherapy meeting in Chicago.

"What is not politically correct to say in public is that both providers
and patients are using these drugs suboptimally," Richman said. Both the
well-educated patients and their doctors closely follow research news
and trends in HAART treatment. They change their treatment plans
constantly, in a never-ending search for minimal side effects, ease of
use and viral suppression. With each switch of drug cocktails, the
patients increase the likelihood of pushing forth mutant HIVs that can
resist the drugs.

Richman fears this continued pattern of chaotic use of anti-HIV drugs
means "we'll end up recapitulating the antibiotic story," referring to
the problem of antibiotic-resistant bacteria.

HIV mutates more rapidly than bacteria, and because the HAART drugs are
not curative, they must be taken forever. Both factors hasten the pace
of emergence of viral resistance. And, "the incentives for the
pharmaceutical industry to develop drugs against resistant HIV virus may
not be there the way it is for antibiotics," Richman said, because the
size of the HIV-positive population in wealthy nations is small.

This begs the question of just how much longer the HAART miracle that
rescued AIDS patients from their death beds in 1996 will last. Roy
Anderson, a mathematical modeler at Oxford University, recently
calculated that each switch of medication, and each interruption in
HAART therapy, has a cumulative effect. If those patients pass their
highly drug-resistant viruses onto sexual partners, the pace of
resistance society-wide accelerates markedly.