February 13, 2003
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.
A Spanish study compared the yearlong experience of patients randomly assigned to continue antiretroviral treatment or to stop and restart only if either CD4 cell count or viral load cutoffs were reached. Over a year, about 60 percent of the treatment interruption group had to start taking medicines again (after an average eight-week break), while 40 percent stayed off the drugs with no obvious ill effects.
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.