Feb. 14, 2001 -- Don't give up too soon on antiretroviral drugs. A report in the Feb. 15 issue of The New England Journal of Medicine suggests that patients still benefit from anti-HIV drugs even when their virus has become highly drug resistant.
"Drug resistance comes at a dramatic cost to the virus," Steven G. Deeks, MD, tells WebMD. "Although HIV can become resistant to all current antiretroviral drugs, such virus does not replicate well. This has major clinical implications: Despite emergence of resistance, stopping drugs should be considered very risky."
People whose first round of anti-HIV drugs fails to keep the virus in check should switch to another round of potent drugs. But this is not an option for patients whose virus already has seen -- and defeated -- all available anti-HIV drugs.
Deeks' team at the University of California, San Francisco, carefully followed a group of people with a lot of experience taking anti-HIV drugs. Most of them were relatively healthy, but their once-potent drug regimens no longer kept the AIDS virus entirely in check. As part of the study, two-thirds of the patients stopped treatment while the others kept taking the same drug regimen.
For study participants who stopped taking anti-HIV drugs, the good news was that tests of HIV taken from their blood showed that drug-resistant virus was being crowded out by drug-sensitive virus. The bad news was that this drug-sensitive virus grew much faster than the resistant virus. Even worse news was that this fast-growing virus could do more damage than the slow-growing, drug-resistant virus. Deeks concludes that continued treatment keeps the more dangerous drug-sensitive virus from coming back.
"The patients we studied have resistance to everything," Deeks says. "For such patients, who have gone through several rounds of treatments, the best thing for them is to continue on a regimen that maintains this poorly fit virus."
This does not apply to people whose virus is resistant to some drugs but still is sensitive to other anti-HIV drugs. For these patients, an early switch in antiretroviral regimen is the best option for controlling the virus.
"My clinical preference has been to try to switch or intensify treatment to preclude further development of resistance," Lisa M. Frenkel, MD, tells WebMD. "[We think] that when you maintain the same regimen for a long time the [resistance] mutations compound, and then you need more drugs to suppress the virus again -- and sometimes you can't suppress it."
Frenkel, director of the pediatric HIV program at the University of Washington in Seattle, wrote an accompanying commentary article published in The New England Journal of Medicine.
"I think there is a role for the Deeks group's approach," she tells WebMD. "What they are doing is they show that highly resistant virus just doesn't replicate as well as [the drug-sensitive] virus. Will it eventually? My experience is 'yes' in some people and maybe 'no' in others. We don't have studies that define the outcome."
The central question is how long taking anti-HIV drugs will continue to work in the face of resistant virus. Deeks, an expert in studying people whose anti-HIV drugs fail, says he has evidence that a person's final drug regimen keeps helping much longer than many people may think.
"We predict that people can continue to ... benefit -- despite ongoing virus replication -- for an average of three years," he says. "That is more or less consistent with what we have been seeing in the five or six years we've been studying people failing antiretroviral therapy."