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'When to Start HAART' Experts Disagree-NEJM Study
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At CROI 2009 the NA-ACCORD group and Dr, Mari Kitahata presented a new analysis:
Summary of Antiretroviral Treatment Naïve Studies from CROI: Still Looking for a Consensus on When to Start - written by Susan J. Little, M.D. Associate Professor of Medicine University of California San Diego, USA - (02/27/09)
"Participants were randomized to immediate or deferred HAART, beginning at the first CD4 cell count >500 cells/mm3 and using an intention to treat analysis. Patients in the immediate treatment group were required to initiate HAART within 1.5 years of study entry or they were censored and considered protocol "failures". Those in the deferred arm were required to initiate ART within 1.5 years of the time that their CD4 cell count fell below 500 cells/mm3"...."The absolute, all cause mortality for patients who deferred ART was 60% higher and relatively stable for the entire 10 year study period compared to those who initiated immediate ART"....."The median CD4 cell count just prior to initiation of ART was 674 for the immediate HAART group and 390 for the deferred HAART group, with a nearly identical viral load response following 12 months of HAART in the immediate and deferred groups (% with VL <500, 79 vs. 73, respectively)." and Doug Richman came to the microphone and said: "I'm really compelled by Mari's data.....the argument that a randomized trial makes any sense bothers me for several reasons, it would take many many years, hundreds of millions of dollars, and wouldn't it make more sense, since most of the patients who present even in the developed world have low CD4 counts, to identify people who need access to care, use all that money and energy to treat people of higher risk"
3 Known Researchers Disagree: Starting HIV Therapy Earlier Saves Lives
03.31.09, 08:00 PM EDT
Study casts doubt on notion that antiretrovirals can be postponed till later in infection
".....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.....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.....Five years ago, if an asymptomatic patient with HIV infection and a CD4+ count of more than 500 cells per cubic millimeter wished to start antiretroviral therapy, most experienced clinicians could have made an excellent case why treatment should be deferred. Today, if a similar patient were eager to start, we should be ready and willing to prescribe therapy - with ongoing careful monitoring of toxic effects that could arise during decades of treatment. Sax & Baden said in their NEJM Editorial........"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..."
"Although the results do not come from a randomized trial, they seem likely to add impetus to a growing movement to start HIV treatment early, according to Paul Sax, M.D., and Lindsey Baden, M.D., both of Harvard Medical School.....The so-called NA-CCORD study "adds to a growing body of data supporting earlier treatment for HIV infection,"....only a full-scale randomized trial -- and several are in the works -- can actually account for all possible confounding factors. For that reason, they argued, the results "cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy.".....Nonetheless, they said, "the supportive evidence for the benefits of earlier therapy continues to increase."....On the other hand, Dr. Kitahata said earlier this year, the study may not have an immediate real-world impact. "One of the difficult things for us in our population of patients is that we see patients presenting very late in disease and even below 350 (CD4 cells per cubic millimeter),"......"Such delays -- combined with the evidence of the benefit of early treatment -- make "strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling," Drs. Sax and Baden said."
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."
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