February 13, 2003
Over the past five years, the argument that HIV-infected people can safely stop taking their medicine for extended periods, and possibly benefit from the breaks, has been alternately championed and rejected. Studies presented yesterday at the 10th Conference on Retroviruses and Opportunistic Infections make clear that the argument is not settled and is actually more muddled than ever.
New research suggests that longer, more open-ended interruptions of treatment may be more useful than presumably safer, shorter breaks for some patients. However, it is uncertain as to whether there is a net benefit to taking the breaks. "It's much more complicated than we think," said John W. Mellors, an AIDS physician at the University of Pittsburgh and a conference organizer. "The message is, people shouldn't be willy-nilly interrupting treatment."
A Thai study compared three strategies: continuous treatment with three drugs; interruption that was allowed to proceed provided the patient's CD4 cell count (key in measuring immune-system robustness) remained above a specified threshold; and week-on/week-off interruptions. Mortality, complications and quality-of-life measures among the three groups yielded no differences at the end of a year. However, patients on the CD4-guided strategy actually did better in controlling viral load in the bloodstream than people in the week-on/week-off group, and only took drugs for about one-third of the year.
Researchers in a U.S. study compared seven rounds of eight weeks on/four weeks off treatment with continuous antiretroviral therapy, testing a theory that the immune system may be boosted by periodic exposure to HIV swarms (occurring when treatment stops), after which the body might suppress the virus more aggressively or without medicine. No evidence of this happening was found. However, the interrupting therapy group was more likely to develop drug-resistant virus, causing researchers to stop enrolling patients in the trial.
Overall, the results of the various studies suggest that frequent interruptions may promote the emergence of drug-resistant virus, especially for patients taking certain drugs that stay in the bloodstream for weeks after the last dosage. Alternatively, it appears that there are people whose immune systems can suppress the virus adequately for long periods of time. It may be possible to identify such people through CD4 or viral load thresholds. A large study through government-sponsored HIV clinics in the United States is testing this idea.
02.13.03; David Brown