GHESKIO Research Published in New England Journal of Medicine: Earlier Is Better for HIV Treatment

 

August 4, 2010

L to R: Drs. Fitzgerald (senior author), Johnson,
Gulick, and Severe (lead author).

Clinical studies at GHESKIO in Port-au-Prince, Haiti, have confirmed that early initiation of antiretroviral therapy significantly increases survival rates among HIV-1 patients. The researchers, which include several of Weill Cornell Medical College's top infectious and tropical disease experts, published the results of the four-year study in the July 15 issue of The New England Journal of Medicine. The study also links early intervention with a decreased rate of incident tuberculosis, a leading cause of death among HIV patients in resource-poor countries, according to the World Health Organization (WHO). The GHESKIO results laid the ground for recent changes in HIV treatment protocols as described in the recent 2010 revision of treatment guidelines publish by WHO.

The paper's authors include Senior Physician at GHESKIO Patrice Severe, MD, a graduate student in the WCMC Program in Clinical Epidemiology and Health Services Research; Associate Professor of Medicine Daniel W. Fitzgerald, MD, who leads clinical research and public health initiatives in Haiti and Tanzania; Professor of Medicine and Chief of the Division of Infectious Diseases Roy M. Gulick, MD, an early champion of antiretroviral "cocktail" therapy for HIV; B.H. Kean Professor of Tropical Medicine Warren D. Johnson, Jr., MD, who is Director of the Center for Global Health; and Professor of Medicine Jean W. Pape, MD, Founding Director of GHESKIO.

Previous to the GHESKIO study, standard treatment practice for HIV patients indicated beginning antiretroviral therapy (ART) only at a certain clinical threshold: when the measure of a patient's CD4+ T cells — a critical immune-system cell — dips below 200 cells per cubic millimeter. 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. 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.

Between 2005 and 2008, the investigators recruited 816 HIV-1-infected subjects. All subjects 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. Subjects were randomly divided into two groups; those in the first group began ART immediately, those in the second group (the control) 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.

The results speak for themselves. Twenty-three subjects in the control group died, compared to six in the early-treatment group — a 75 percent decrease. In the control group, 36 subjects developed incident tuberculosis, compared to 18 in the early-treatment group — a 50 percent decline. CD4 counts were also revealing. From a median count of 281 at the beginning of the study, the early-treatment group ended the study at 520, a remarkable improvement. The control group ended the study slightly worse, at 270.

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.

Founded in 1982, The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) is a nongovernmental research and training center internationally recognized for its pioneering work in the treatment of HIV and AIDS-related illnesses. Since its inception, GHESKIO has never closed its doors to patients, not even during the recent 7.0-magnitude earthquake that struck Haiti.


Top of page