Study casts doubt on notion that antiretrovirals can be postponed till later in infection
WEDNESDAY, April 1 (HealthDay News) -- Initiating HIV treatment before the patient's immune system is too badly compromised can dramatically improve survival, a new study finds.
The finding may help settle a debate among AIDS experts as to whether powerful antiretroviral drug therapy can be deferred until later in the infection process.
On the one hand, experts worry that starting patients early on the potent drug cocktail could increase the medicines' toxic effects. But if treatment begins too late, the drugs might not be as effective.
Because patients must continue to take these drugs for the rest of their lives, weighing toxicity against efficacy has been a difficult balance.
"The optimal time to initiate therapy for asymptomatic HIV-infected individuals has been unclear," explained lead researcher Dr. Mari M. Kitahata, of the University of Washington, Harborview Medical Center, in Seattle.
But in the new study, the Seattle group found that, compared with patients who started treatment early, patients who delayed therapy boosted their odds of dying by either 69 percent or 94 percent, depending on how low the patient's CD4 blood cell count was.
The study was released ahead of schedule April 1 by the New England Journal of Medicine. It will appear in the journal's April 30 print issue.
For the study, Kitahata's team collected data on 17,517 American and Canadian HIV patients who were receiving treatment from 1996 through 2005. Patients were classified by their CD4+ immune T-cell count, a measure of the strength of the immune system. As HIV disease progresses, the CD4 count drops.
Participants were divided into two groups: one group had CD4 counts between 351 and 500 cells per millimeter, while the other group was comprised of patients with CD4 counts above 500.
In a first analysis, involving 8,362 of the patients, 25 percent started therapy when their CD4 counts were between 351 to 500, while the other 75 percent deferred treatment until their CD4 counts fell below that threshold.
Patients who deferred treatment experienced a 69 percent increase in their risk of dying compared with those who began treatment, the researchers found.
In a second analysis, this time including 9,155 patients, 24 percent started treatment at CD4 counts of more than 500 cells per millimeter, while the other 76 percent delayed therapy till after their counts fell below that threshold. In this group, patients who deferred therapy experienced a 94 percent rise in death risk compared to those who began their therapy earlier.
"Our study adds to the growing evidence that support earlier initiation of therapy to improve survival," Kitahata said. "We think antiretroviral treatment should be started when the CD4 count is above 500. I feel these data are strong enough that I would start a patient who is ready and willing to begin therapy at a CD4 count above 500 and certainly between 350 and 500," she said.
Dr. Paul E. Sax, from the division of infectious diseases and the department of medicine at Brigham and Women's Hospital in Boston, said the study does seem to tilt the argument in favor of earlier treatment.
"This study provides us with some of the strongest data that earlier treatment for HIV infection prolongs survival," said Sax, who authored an accompanying journal editorial. "While this study alone doesn't prove the point, it adds to an accumulating body of data that earlier HIV therapy is preferred to waiting."
Five years ago, if a patient with HIV had no symptoms and a CD4 cell count greater than 500, most experienced HIV clinicians would in general counsel not to initiate therapy, due to concerns about drug toxicity, Sax said. Studies such as this suggest that probably all patients with HIV would benefit from treatment. "We'll need to continue monitoring for drug side effects," he said.
Another expert agreed.
"It must still be recognized that the long-term side effects of the anti-HIV drugs we now use are unknown, and could alter this recommendation after longer patient follow-up," said Dr. Jeffrey Laurence, a professor of medicine at Weill Cornell Medical College in New York City.
And A. David Paltiel, an associate professor of public health at Yale University School of Medicine, said the findings highlight one more important point: HIV testing.
"We've got to be doing more testing," Paltiel said. "There are some 250,000 to 300,000 Americans who don't know that they are HIV infected and therefore cannot enjoy the benefits of earlier intervention."
For more information on HIV/AIDS, visit the U.S. National Institutes of Health.
SOURCES: Mari M. Kitahata, M.D., M.P.H., University of Washington, Harborview Medical Center, Seattle; Paul E. Sax, M.D., division of infectious diseases and the department of medicine, Brigham and Women's Hospital, Boston; Jeffrey Laurence, M.D., professor of medicine, Weill Cornell Medical College, New York City;A. David Paltiel, Ph.D., associate professor of public health, Yale School of Medicine, New Haven, Conn.; April 1, 2009, New England Journal of Medicine, early online edition
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