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Earlier start to antiretrovirals cuts mortality 50%. (At CD4 Cell Counts Between 351 and 500).

SEATTLE -- Initiating highly active antiretroviral therapy when the patient still has a CD4 cell count between 351 and 500 cells / [micro]L may be associated with less mortality than waiting until the CD4 count drops below 350 cells/[micro]L, as is often the standard practice, Dr. Frank J. Palella said at the Ninth Conference on Retroviruses and Opportunistic Infections.

Starting highly active antiretroviral therapy (HAART) when the CD4 cell count was between 351 and 500 cells / [micro]L reduced mortality by 50%, compared with waiting until the CD4 count dropped to between 200 and 350 cells/[micro]L, reported Dr. Palella of Northwestern University, Chicago.

Current U.S. guidelines, issued in early 2000, recommend initiating HAART in asymptomatic individuals when the CD4 cell count falls below 350 cells/[micro]L.

But Dr. Palella declined to say that the finding indicates that the guidelines need to be reevaluated. He noted that any benefit from starting therapy earlier must be weighed against the fact that patients who start earlier may be more likely to experience patient burnout, possible drug resistance, and the adverse effects of HAART medications such as hyperlipidemia.

Some previous evidence has suggested that when CD4 counts fall below a certain level, the immune system does not fully recover even when HAART therapy brings the CD4 count back into acceptable ranges. But that level has not been defined.

The study included more than 800 patients in the HIV Outcomes Study for whom an initial CD4 count and the timing of initiation of HAART therapy were known. There were 126 patients with CD4 counts between 501 and 750 cells/[micro]L, 315 patients with counts between 351 and 500, and 377 patients with counts between 201 and 350. Mortality was assessed in patients who started therapy while their CD4 counts were within that level and in those who delayed therapy.

In each group, more than two-thirds of those who delayed later started therapy when their CD4 counts were within the next lower level. There were no significant differences in demographics between those who initiated before dropping out of their level and those who delayed. Follow-up ranged from a median of about 5-6 years for those in the group with 501-750 CD4 cells to a median of about 3 years for those in the group with 201-350 cells. But there was no significant difference in the median followup of those who initiated and those who delayed within any of the groups.

Overall, Dr. Palella said the findings show a clear benefit for starting therapy before the CD4 count drops below 200 cells/[micro]L, the possibility of a benefit for starting when the CD4 count is between 351 and 500 cells, and nothing that would indicate a benefit for starting when the CD4 count is between 501 and 750 cells.

In the 201-350 cells group, 325 initiated and 52 delayed; the mortality rate was 20.8 deaths per 1,000 patient-years for initiating, compared with 70.6 per 1,000 patient-years with delay Of those with 351500 cells, 229 initiated and 86 delayed; the rates were 10.7 and 18.2, respectively In the group with 501-750 cells, 54 initiated and 72 delayed; the rates were 7.5 and 3, respectively.

The highest group had only three deaths, none of which appeared to be HIV related, which makes it impossible to come to any conclusions for that group, Dr. Palella said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

Data on viral load yielded similar evidence of benefit for starting HAART earlier, he reported.

In the lowest CD4-cells group, 62% of patients who initiated therapy before dropping below 200 cells/mL subsequently achieved an undetectable viral load, compared with 46% of those who delayed. Similarly 68% of those who started therapy between 351 and 500 cells achieved an undetectable viral load, compared with 56% of those who delayed. And 65% of those who started therapy between 501 and 750 cells achieved an undetectable viral load, compared with 61% who delayed.
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Comment:Earlier start to antiretrovirals cuts mortality 50%. (At CD4 Cell Counts Between 351 and 500).
Author:Kirn, Timothy F.
Publication:Family Practice News
Article Type:Brief Article
Geographic Code:1USA
Date:May 15, 2002
Words:673
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