SanFranChron

HIV's drug resistance increasing rapidly UC study forecasts 42% of S.F. cases affected by 2005

Sabin Russell, Chronicle Medical Writer Friday, August 31, 2001

Researchers at the University of California are forecasting that 42 percent of HIV infections in San Francisco will be resistant to current AIDS drugs by 2005, further complicating efforts to keep the rapidly mutating virus in check.

"Forty-two percent is a lot of resistance. It will certainly be a challenge if we do not get new drugs developed," said Dr. James Kahn, an AIDS specialist at San Francisco General Hospital and senior author of the report, published yesterday in the journal Nature Medicine.

Resistant strains of HIV are developed when the virus mutates into forms that aren't suppressed by a combination of powerful antiviral drugs -- the so- called cocktails that have cut the AIDS death rate in half since their introduction in 1996.

The model shows drug resistance among all people living with HIV -- including both new and existing infections -- growing from zero in 1996 to 28. 5 percent in 1999, and reaching 42 percent in 2005.

Limited data from San Francisco General Hospital clinics suggest that the model has been accurately tracking the proportion of drug resistant cases -- which in 1999 accounted for 28 percent of the hospital's HIV caseload.

Once resistance appears, doctors can switch to new combinations. But for a patient, it can signal a slide from robust health to a life with increasingly less desirable medical choices. "Subsequent treatments rarely work as well as the first," said Kahn, an associate professor at the University of California at San Francisco.

While doctors agree AIDS drug resistance is something to be avoided, other UCSF researchers have uncovered evidence that the mutant viral strains resistant to AIDS drugs are less dangerous than their "wild" counterparts.

WEAKENED VIRUS

"Our work clearly indicates that, as the virus becomes drug resistant, its capacity to destroy the immune system is also weakened," said Dr. Steven Deeks,

an AIDS clinician at San Francisco General Hospital.

Deeks said it is still preferable to have an infection held in check by effective AIDS drugs, but that the development of a resistant strain is by no means a return to the days when the original virus could run amok and wipe out the body's natural defenses.

"From the onset of drug resistance, it takes a patient an average of three years to lose the (infection fighting) T-cells they gained from antiviral therapy," Deeks said.

That suggests that, while those with resistant virus are worse off than they were before developing the mutant strains, the newer viruses will take longer to do their lethal work -- perhaps long enough for new therapies to come to the rescue.

The prediction is the product of a complex computer modeling program developed by UCLA biomathematician Sally Blower, co-author of the paper, who previously conducted her research at UCSF. Her program is based on systems originally developed to predict the risk of nuclear plant meltdowns. Blower has been applying the technique to infectious diseases for nearly a decade.

"We take her work very seriously," said San Francisco Department of Public Health epidemiologist Willi McFarland. The city estimates there are currently 18,000 residents living with HIV. "If lives are shortened by a few years because of drug resistance, it could add up to thousands of years of life lost in the city," he said.

ACQUIRING VIRUS

Blower notes that a resistant strain can be acquired in one of two ways: an existing viral infection that responds to drug treatment can mutate into an unresponsive one, or an already drug-resistant strain can be transmitted to a previously uninfected person.

A key finding of her computer analysis is that the latter scenario -- transmission of resistant strains -- is "a relatively minor public health problem."

Currently, the model estimates that only 8 percent of new HIV cases in San Francisco in 2000 would be drug-resistant -- a finding that is also consistent with the 9 percent recorded in city clinics. By 2005, that number is expected to grow to 16 percent.

The fear that a new epidemic of drug-resistant virus could be unleashed is largely unfounded, she said.

The computer model did not take into account possible transmission of drug- resistant strains to those already infected with virus susceptible to antiviral treatment.

Such "reinfection" is a theoretical risk of unprotected sex between two HIV positives -- activity that surveys indicate is on the rise. But Kahn and Blower said there is little clinical evidence to date to suggest that reinfection is occurring, and hence it was appropriate to leave that out of the equation.

HEALTH STRATEGY

Based on the model, Blower said the most important public health strategy is to focus on ways to reduce drug resistance in the already infected. And she stressed the need to develop new therapies for patients with drug-resistant strains.

Martin Delaney, founding director of the San Francisco advocacy group Project Inform, said the prediction of high rates of drug resistance is not surprising.

"If there were no new drugs in the pipeline, this would be a significant figure," he said. However, there are two new medications under development that appear to work against strains that resist current protease inhibitors. "This is a problem that ultimately will be controllable," he said.

-- Anonymous, August 31, 2001