Drug Regimen with Short Pauses Controls HIV and Could Lower Costs, Toxicity
Antiretroviral drugs for HIV infection usually are taken daily, and interrupting treatment for long periods of time has proven detrimental. However, a clinical trial in Uganda has found that pausing antiretroviral therapy (ART) for just two days every week is at least as effective as taking ART continuously over a 72-week period. In addition, the intermittent regimen was associated with less drug toxicity relative to continuous ART. These findings, reported on April 22 in PLoS ONE, may have implications for increasing the number of HIV-infected individuals on ART in resource-limited settings.
Led by Mark R. Dybul, M.D., and funded by the National Institute of Allergy and Infectious Diseases, part of NIH, the study investigators enrolled 146 HIV-infected participants between 2002 and 2005. Participants were assigned at random to take ART on one of three schedules: continuously, in a cycle of five days on and two days off, or in a cycle of seven days on and seven days off. Investigators discontinued the third group in 2004 after a data and safety monitoring board found that HIV treatment failed for 31 percent of the participants. In the end, 52 people taking ART on a cycle of five days on and two days off, and 51 people taking ART continuously completed the planned 72 weeks of participation.
Treatment failed for 21.6 percent of the continuous therapy group, but for only 11.5 percent of the intermittent therapy group. Also, the rates of certain drug-related side effects—namely, abnormal fat distribution and a build-up of lactic acid in the blood—were significantly higher in the continuous therapy group than in the intermittent therapy group. Both forms of therapy boosted participants’ immune system health to similar levels.
The study authors note the potential cost savings of an intermittent ART strategy that is at least as effective as continuous therapy and also less toxic. In addition, the authors suggest that an ART cycle of five days on drugs and two days off would mesh with programs in which patients must be directly observed taking their medicines—for instance, children who take their antiretroviral drugs at school five days a week. However, the authors stress that further study is needed to determine the long-term health effects of pausing ART for two days a week before this regimen can be recommended for use outside of a research setting.
For more information about this study, see Reynolds et al. 2010. A randomized controlled trial of short course intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda. PLoS ONE 5(4): e10307. DOI: 10.1371/journal.pone.0010307.