One of the key decisions faced by people living with HIV, and by their health-care providers, is when to start treatment.
Some recent studies have found that starting highly active antiretroviral therapy earlier is better. Now a new study led by researchers at the University of North Carolina at Chapel Hill finds that there may be a limit to how early the therapy, known as HAART, should start.
The new results could help determine where the starting line for antiretroviral therapy should be drawn, said Michele Jonsson Funk, Ph.D., research assistant professor in the UNC Gillings School of Global Public Health and lead author of the study, which is published in the Sept. 26, 2011 issue of the journal Archives of Internal Medicine.
"The drugs used to treat HIV are expensive, treatment is life-long, and the side effects can be serious," Jonsson Funk said. "So we really need to know if the patient's investment will pay off, how large the benefit is likely to be, and how long it will take to realize it.
"The bottom line from these findings, taken together with other studies published over the last few years, is that initiating therapy when the patient's CD4 count is between 350 and 500 appears to be beneficial over the long term. But for patients with a CD4 count above 500, the jury is still out."
The CD4 count measures how many CD4 cells -- a type of white blood cell that fights infection -- are in a cubic milliliter of blood. In patients infected with HIV, the virus that causes AIDS, a lower CD4 count is usually associated with more advanced disease, while a higher CD4 count is seen as a sign of better health.
There is wide agreement among researchers and health-care providers that HIV patients with CD4 counts below 350 should be on antiretroviral therapy, Jonsson Funk said. However, there is still uncertainty regarding how much patients benefit -- if at all -- by starting treatment at higher CD4 counts. This study was aimed at answering that question.
The researchers found slower progression of the disease among patients whose CD4 counts were between 350 and 499 when they began treatment. The findings also showed a 41 percent reduction in the relative risk of AIDS or death for patients who started receiving HAART with CD4 counts of 200 to 349; and reductions in the risk of death of 29 percent and 49 percent associated with HAART initiation at CD4 counts of 200-349 and 350-499, respectively. However, there appeared to be no benefit to initiating treatment at CD4 counts between 500 and 800.
The results are based on statistical analyses that Jonsson Funk and study co-authors performed on data collected from 9,455 HIV patients in Europe, Australia and Canada between 1996 and 2009. The patients were enrolled in the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) Collaboration.
UNC co-authors of the study are Stephen R. Cole, Ph.D.; James C. Thomas, Ph.D.; Alice D. White, Ph.D. and Joseph J. Eron Jr, M.D. All are in the epidemiology department in the UNC Gillings School of Global Public Health except for Eron, who is a professor in the UNC School of Medicine and a member of the UNC Center for AIDS Research.
Eron was also a co-author of a landmark, UNC-led HIV prevention study called HPTN 052, which found that early treatment (CD4 count: 350-550) of HIV-infected people with combination antiretroviral therapy led to a 96 percent reduction in transmission of the virus to their uninfected partners and a 40 percent reduction in their own risk of developing a serious illness. Those results are consistent with the results reported by Jonsson Funk.
Co-authors from other institutions are Jennifer S. Fusco, EpiQuest Sciences Inc., Libertyville, Ill.; Kholoud Porter, Ph.D., Medical Research Council, London, England; Jay S. Kaufman, Ph.D., McGill University, Montreal, Quebec, Canada; Marie Davidian, Ph.D., North Carolina State University; and Katherine E. Hartmann, M.D., Ph.D., Vanderbilt University Medical Center.
- Writing Committee for the CASCADE Collaboration. Timing of HAART Initiation and Clinical Outcomes in Human Immunodeficiency Virus Type 1 Seroconverters. Archives of Internal Medicine, 2011; DOI: 10.1001/archinternmed.2011.401
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