Brief HIV Cameos No Threat To Therapy

Low viral levels don't necessarily mean treatment fails

TUESDAY, July 10, 2001 (HealthDayNews) -- The current strategy for treating HIV is to drive the virus to levels beneath the reach of even the most sophisticated detection methods. Yet completely removing HIV from the bloodstream of infected patients may not be necessary to adequately suppress the AIDS-causing virus, new research shows.

Two reports in the July 11 Journal of the American Medical Association suggest that cameo appearances of HIV in the blood don't automatically signal the failure of drugs to quash the infection, nor do they signal the rise of resistant virus.

While the results are potentially significant, AIDS experts caution that longer studies of the same patients may not turn out to be as promising. Between 650,000 and 900,000 Americans are infected with HIV, reports the Centers for Disease Control and Prevention.

In one study, led by Dr. Diane Havlir of the University of California in San Diego, researchers reviewed data from two trials of HIV-positive patients receiving triple-drug therapy who had intermittent viremia, or evidence of virus in their blood.

Periods of viremia were common, occurring in 30 percent to 40 percent of 241 patients, 101 of whom were consistently on the three-drug combination of indinavir, zidovudine and lamivudine.

But upticks in viral loads didn't predict in whom treatment would fail. During the 15-month study, about 10 percent patients with viremia failed therapy, compared with nearly 14 percent of those without the spikes.

In the second, smaller trial, transient viremia occurred in six of 13 patients who'd achieved suppression of HIV with the indinavir-zidovudine-lamivudine combination. Yet again, periodic surges in viral levels weren't associated with treatment collapse over 4.5 years of follow-up.

"Treatment changes may not be necessary to maintain long-term virologic suppression with low-level or intermittent viremia," the scientists write.

In a second journal report, researchers at Johns Hopkins University in Baltimore say they've found that "archival" or previously present resistant virus appears to be a leftover from earlier therapy and doesn't signal a weakening of current treatment.

The study followed 18 patients, including seven children, receiving highly active anti-retroviral therapy (HAART) for long-term suppression of HIV. Genetic tests revealed no new signs of resistance in the patients' virus strains. However, the researchers say they did turn up virus particles that showed resistance to earlier but now abandoned therapies.

"That resistance persisted in the absence of continued drug exposure, but new resistance did not form," says Dr. Deborah Persaud, an expert in pediatric infectious diseases and a co-author of the paper. Although very low levels of resistant HIV can be found by highly sensitive testing, they don't appear to pose a threat to HAART. "This is the first study to demonstrate that HAART is effective in preventing evolution of drug resistance."

On the other hand, Persaud say the presence of these stray, hearty virus particles suggests that round-robin HIV therapy that returns to earlier, unsuccessful drugs might not be the best approach in patients who fail HAART.

In an editorial accompanying the journal articles, Dr. Steven Deeks, an AIDS expert at the University of California in San Francisco, writes that "complete viral suppression does not appear to be a prerequisite for durable virologic and, presumably, clinical benefit."

Deeks says the question is how much suppression is needed before treatment becomes durable. "Partially suppressive regimens that achieve [this threshold], are well tolerated, and preserving future options may be preferred to more potent regimens that are not as well tolerated ... . Thus, it is possible that using the most potent regimen possible to completely prevent all viral replication may cause more harm than benefit."

Deeks says AIDS doctors are recognizing that total suppression of HIV isn't the holy grail of treatment and have probably begun applying that approach to their patients. "This is HIV. Things move quickly," Deeks says.

What To Do: For more on AIDS, visit the Centers for Disease Control and Prevention, or the World Health Organization.

SOURCES: Interviews with Deborah Persaud, M.D., assistant professor of pediatrics, Johns Hopkins University, Baltimore, and Steven Deeks, M.D., assistant professor, University of California at San Francisco; July 11, 2001 Journal of the American Medical Association
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