NIAID Halts Trial on Antiretroviral Drug Conservation Strategy After Findings Show Method Increases HIV-Positive Patients’ Risk of AIDS, Death
The National Institute of Allergy and Infectious Diseases on Wednesday announced it ended enrollment in a clinical trial comparing daily antiretroviral therapy with a drug-conservation strategy, which involves taking medication intermittently, after findings showed the conservation strategy increased HIV-positive patients' risk of developing AIDS or dying, Reuters reports (Reuters, 1/19). The Strategies for Management of Antiretroviral Therapy trial -- which involved 318 sites in 33 countries -- began enrolling patients in January 2002 and included 5,472 HIV-positive participants when the trial was suspended on Jan. 11 (NIAID release, 1/18). SMART trial volunteers were randomly assigned to a daily antiretroviral therapy regimen or an episodic treatment strategy, which called for taking medication only when CD4+ T cell counts dropped below a specific level, the AP/Miami Herald reports. Previously, smaller studies indicated that taking monitored breaks from daily antiretroviral treatment might control the progression of HIV while reducing some of the drugs' side effects, as well as lowering costs of the treatment regimens (Neergaard, AP/Miami Herald, 1/19). However, interim studies of the NIAID trial conducted earlier this month by the independent Data and Safety Monitoring Board showed that participants who took their medication on an irregular basis were more than twice as likely to experience increased progression of the virus or death compared with those on a daily treatment regimen (NIAID release, 1/18). Patients taking episodic treatment also were more likely to experience cardiovascular and kidney complications as well as liver disease, all of which also have been related to antiretroviral drug use (Smith, Boston Globe, 1/19).
"[I]t's disappointing news," Jose Zuniga, president of the International Association of Physicians in AIDS Care, said, adding that these results "should signal us to invest even more in developing the next generation of antiretroviral drugs," some of which might make intermittent treatment a possibility for the future (AP/Miami Herald, 1/19). "We were surprised to learn that in the short term, episodic antiretroviral therapy carries such an increased risk without evidence of sparing patients the known side effects associated with [antiretroviral therapy]," Wafaa El-Sadr of the Harlem Hospital Center and Columbia University in New York, who was working on the trial, said. "It is important to emphasize that the cessation of SMART does not necessarily mean that all treatment strategies involving interruptions of antiretroviral therapy are dangerous, just that the specific approach employed by the SMART study design was less successful at preventing clinical events than continuous treatment," the Treatment Action Group said in a statement, adding, "There is a large body of data suggesting that individuals who initiate therapy with relatively high CD4[+ T cell] counts can safely interrupt therapy" (Reuters, 1/18).