HIV/AIDS Treatment Interruption Has Adverse Effect on Some Patients With Drug-Resistant HIV Strains, Study Says
HIV/AIDS patients who have drug-resistant HIV strains and who temporarily stop taking their antiretroviral treatments and then switch to a different regimen are more than twice as likely experience their disease progression, compared with similar patients who continuously take their medication, according to a study published in today's issue of the New England Journal of Medicine, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 8/28). Some patients with drug-resistant HIV strains and their doctors hoped that interrupting antiretroviral therapy regimens could strengthen a patient's immune system, in part by allowing the drug-resistant virus to mutate back to a less resistant form. The "drug holidays" also might have spared patients some of the "frequent and often serious" side effects related to antiretroviral drug use, the New York Times reports (Altman, New York Times, 8/28). Dr. Jody Lawrence of the University of California-San Francisco and colleagues randomly assigned 138 patients with multi-drug-resistant HIV and HIV RNA levels of more than 5,000 copies per milliliter to a four-month structured interruption of treatment, followed by a change in antiretroviral treatment, and 132 patients with similar levels of drug resistance to receive an immediate change in their treatment regimens. Researchers assessed disease progression, death, changes in drug-resistance patterns, CD4+ T cell counts, HIV RNA levels and quality of life for both groups (Lawrence et al., NEJM, 8/28).
Researchers found that patients who took breaks between regimens saw a "precipitous drop" in their CD4+ T cells, putting them at an increased risk for contracting opportunistic infections, according to the Chronicle (San Francisco Chronicle, 8/28). After 12 months, 22 patients in the structured treatment interruption group had either died or experienced disease progression, compared with 12 patients in the control group, according to the study (BBC News, 8/27). There were eight deaths in each group (NEJM, 8/28). Researchers also found that the virus completely or partially reverted to a more drug-sensitive form, or wild-type virus, in 64% of the patients whose treatment was interrupted, Reuters reports (Emery, Reuters, 8/27).
"Our results indicate that this strategy does not work and should be avoided by this group of HIV-infected individuals. Continuing therapy guided by HIV drug-resistance testing proved to be a better approach," Lawrence said (Washington Post, 8/28). Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which sponsored the trial, said, "For individuals who are being successfully treated with anti-HIV medications, other studies have shown that cycles of treatment interruptions for shorter periods may be of potential benefit to conserve medications and reduce drug-related toxicities," adding, "The general message from this study is if you have drug-resistant virus, stopping therapy does not help, period, because the virus rebounds and the infection progresses" (New York Times, 8/28). Dr. Bernard Hirschel, an AIDS expert at the Hopital Cantonal Universitaire in Geneva, said in an accompanying NEJM editorial that clinicians should follow the findings of this study; however, he added that "[p]artial or complete interruption of treatment may still have a role" in HIV treatment but perhaps the duration of interruption should be shortened. Hirschel concluded, "This interesting approach to treatment awaits clinical trials. Thus, for the time being, unless there are unbearable side effects, patients should continue treatment while awaiting" another option (Hirschel, NEJM, 8/28).
NPR's "All Things Considered" yesterday reported on the NEJM study and a study published in the Sept. 5 issue of the journal AIDS that examined the relationship between treatment adherence, duration and the development of drug-resistant HIV. The segment includes comments from Dr. David Bangsberg of the University of California-San Francisco, lead author of the AIDS study, and Ken Mayer, a professor of medicine and community health at Brown University (Silberner, "All Things Considered," NPR, 8/27). The full segment is available online in RealPlayer.