Interruptions in antiretroviral treatment increases risk of developing AIDS-related diseases

Interruptions in an HIV-positive person's antiretroviral treatment regimen can increase the risk of developing AIDS-related diseases and sometimes can be fatal, according to a study published Thursday in the New England Journal of Medicine, the Los Angeles Times reports.

The study -- known as Strategies for Management of Antiretroviral Therapy, or SMART -- was led by NIH and involved 5,472 HIV-positive people in 33 countries (Chong, Los Angeles Times, 11/30). The study began in January 2002 but was halted at the beginning of this year after preliminary results indicated that the mortality rates among the 2,720 participants who were in the treatment-interruption group were significantly higher, the San Francisco Chronicle reports. According to the Chronicle, participants in the treatment-interruption group stopped taking antiretrovirals when their CD4+ T cell counts were above 400 and restarted drug therapy when their T cell counts were below 250. The study found that those in the treatment-interruption group were 1.9 times more likely to die and had a substantially higher risk of becoming ill from AIDS-related diseases compared with those who did not interrupt their antiretroviral regimens (Russell, San Francisco Chronicle, 11/30). According to the study, 120 participants in the treatment-interruption group died or developed AIDS-related diseases, while 47 participants in the continuous-treatment group died during the study period (Los Angeles Times, 11/30). The study also found that 8% of all deaths were caused by AIDS-related diseases. The most common known cause of death among the participants was cancer, followed by cardiovascular disease and complications from substance abuse, the study found (San Francisco Chronicle, 1130). In addition, participants in the treatment-interruption group were 1.8 times more likely to develop serious kidney, heart or liver problems than the continuous-treatment group. Although researchers expected the rate of cardiovascular disease to be lower in the treatment-interruption group because heart problems are commonly reported side effects of antiretrovirals, the study found that 48% of participants in the treatment-interruption group developed cardiovascular problems, compared with 31% in the continuous-treatment group (Los Angeles Times, 11/30).

Reaction
Donald Abrams, a researcher at the University of California-San Francisco, said it was difficult to explain why more people died in the treatment-interruption group because the actual number of deaths was low, the Chronicle reports. He added that one reason is that HIV or the inflammation it causes can negatively affect HIV-positive people in ways not fully understood (San Francisco Chronicle, 11/30). "This was a big surprise," James Neaton of the University of Minnesota said, adding, "Treatment may increase the risk" of heart, liver and kidney disease, "but the absence of treatment appears to increase the risk even more" (Emery, Reuters U.K., 11/29). Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said, "I think, for practical purposes, this is the end" of the stop-and-start antiretroviral treatment strategy (Los Angeles Times, 11/30).

Additional Articles
NEJM in its Nov. 30 issue ran other HIV/AIDS-related articles. Headlines appear below.

• "HIV/AIDS in Tanzania -- Realities on the Ground" (Zeeman, NEJM, 11/30).
  
• "Getting Smarter -- The Toxicity of Undertreated HIV Infection" (Currier/Baden, NEJM, 11/30).
  
• "Pioneers in AIDS Care -- Reflections on the Epidemic's Early Years" (Bayer/Oppenheimer, NEJM, 11/30).