One Week On, One Week Off Antiretroviral Regimen Could Reduce Cost and Toxicity, Does Not Appear to Reduce Drugs’ Effectiveness, Study ShowsCycling antiretroviral treatment in a seven days on, seven days off pattern does not appear to reduce the drugs' effectiveness, but can reduce cost and toxic side effects, according to a study conducted by researchers at the National Institute of Allergy and Infectious Diseases appearing in today's early edition of the Proceedings of the National Academy of Sciences. NIAID Director Anthony Fauci and Mark Dybul, NIAID assistant director for medical affairs, led a small-scale investigation of "structured intermittent therapy" in 10 HIV-positive individuals. All 10 participants had been receiving standard continuous highly active antiretroviral therapy, had HIV plasma levels below 500 copies per mL and CD4+ T cell counts of at least 300 cells/mm3 prior to beginning therapy. Participants were then placed on combination therapy consisting of stavudine, lamivudine, indinavir and ritonavir for seven days at a time. After seven days on the medication, participants took no drugs for an additional seven days before beginning their next drug cycle. The on-off cycle was repeated for 32 to 68 weeks. Study participants did not experience an increase in viral load in their blood or lymph nodes, CD4+ T-cell counts remained at pre-study levels, and there were no signs of drug resistance. However, there were significant decreases in serum cholesterol and triglyceride levels -- 22% and 51% respectively after 24 weeks on therapy (NIH release, 12/3). High cholesterol and triglyceride levels, which often lead to abnormal fatty deposits on the body, are a major side effect of antiretroviral drugs (Recer, AP/Contra Costa Times, 12/4). Intermittent therapy may help patients avoid taking cholesterol medications and may keep them from developing heart disease, Dybul noted.
Putting Theory Into Practice
If the findings are confirmed by large-scale trials now underway, it could mean "enormous" savings for HIV/AIDS patients, particularly in the developing world, USA Today reports (Fackelmann, USA Today, 12/4). Speaking on NPR's "All Things Considered" yesterday, Dybul noted that the current cost of antiretroviral treatment in many developing nations is between $350 and $500 per person per year. However, "[i]f you can get away with 50% less drugs without sacrificing clinical efficacy, and, in fact, maybe having clinical benefit in terms of toxicity, you now can reduce the cost, perhaps to $175 per person," he explained (Knox, "All Things Considered," NPR, 12/3). Hans Binswanger of the World Bank noted that the current $350 to $500 price tag, while below Western prices, was still prohibitive for many people and said he "welcome[d]" the study results, as confirmation of the results will make it possible to expand treatment to more people (AP/Contra Costa Times, 12/4).
Don't Try This at Home
In an accompanying commentary, Diane Havlir, an AIDS researcher at the University of California-San Diego, cautioned against reading too much into the study findings, noting that the study was only carried out with 10 people and urging doctors to wait for the results of the larger trials currently underway before making treatment recommendations. Results from those trials should be available within "a year or more." Fauci warned HIV patients not to attempt to pattern their own course of treatment after the study, explaining that the treatment "worked only when the volunteers followed the plan to the letter." Variations in the treatment schedule could lead to a rise in viral levels or cause viral mutations, he added (USA Today, 12/4). An audio archive of yesterday's "All Things Considered" is available online.