Prompted by clinical research into the early initiation of antiretroviral therapies for HIV performed at the GHESKIO clinic in Port-au-Prince, Haiti, the World Health Organization (WHO) has revised its treatment protocols for HIV patients.
Final results from the four-year study, led by Weill Cornell Medical College's infectious and tropical disease experts, were published in the July 15 issue of the New England Journal of Medicine.
The research indicates that rather than waiting until a patient's CD4+ T cells fall below the 200 cells per cubic millimeter threshold, as the previous WHO guidelines suggested, immediately initiating antiretroviral therapy (ART) greatly improved the efficacy of those medications. The study also linked early intervention with a decreased rate of incident tuberculosis, a leading cause of death among HIV patients in resource-poor countries.
"Beginning antiretroviral therapy before T-cell counts drop to 200 will save lives. In developed countries, HIV has, in recent years, become a manageable, chronic disease rather than the death sentence it was just a decade ago. These results further strengthen the assertion that the right therapies, initiated as soon as possible, can hold the virus at bay," says Dr. Warren Johnson, study co-author and director the Center for Global Health and the B.H. Kean Professor of Tropical Medicine at Weill Cornell Medical College.
In December 2009, seven months after the researchers concluded their data gathering, the World Health Organization and the United States Department of Health and Human Services both updated their HIV treatment recommendations to reflect the GHESKIO conclusions: that for HIV-1-infected patients, ART is best initiated at a CD4 count of 350 or lower.
Between 2005 and 2008, the investigators recruited 816 HIV-1-infected patients at the GHESKIO clinic. All had CD4 counts between 200 and 350, had no history of AIDS illness, and had never received ART, a drug cocktail that works by inhibiting the enzyme that enables HIV to hijack healthy cells and replicate. The cocktail in this case comprised zidovudine, lamivudine and efavirenz. Study participants were randomly divided into two groups; those in the first group began ART immediately, and those in the second (control) group received ART only when their CD4 counts measured 200 or lower -- standard treatment protocol. Of the 408 subjects in the control group, 160 reached that point and received ART during the study.
"Clinical evidence has long shown that HIV patients become vulnerable to life-threatening illness long before their CD4 count hits 200, but no one had yet definitively established that ART is effective before that crucial number," says Dr. Patrice Severe, study lead author and graduate student in the Weill Cornell Medical College Program in Clinical Epidemiology and Health Services Research. "Because antiretroviral medications are prone -- much like antibiotics -- to eliciting drug resistance in the target disease, establishing that evidence was essential. The GHESKIO study has filled that gap."
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