Start Treatment Earlier - USA Study
posted: 07/04/2009
A major USA study is recommending people should start treatment even earlier than now. The evidence indicates treatment should be started at a CD4 count of 500. Current UK guidleines are for treatment to start at about 350; the USA also has this start point.
A study showing improved survival of starting antiretroviral treatment earlier than current U.S. recommendations is being reported in the April 30 issue of the New England Journal of Medicine. The study found that not starting HIV patients at a CD4 count greater than 500 cells per cubic millimeter increased risk of death by 94 percent.
George House comment: Figures like this can look rather scary - the risk of death is almost doubled if the start of treatment is delayed to a CD4 level of 350, compared with starting at 500. But remember that the current start point for treatment in the UK is exactly this already, 350. And we see very few early deaths among people in this country who started treatment at 350 - the death rate from HIV has instead plummeted. A death rate twice as high doesn't much matter when the number of early deaths is already low, as it is for people who start treatment at the recommended time and reach an undetectable viral load. The chance of being killed by shark attack is very low. Even if the death rates for shark attacks double, it is still really unlikely. The same principle applies to HIV deaths in this country.
"The question of when to start antiretroviral therapy has been one of the key controversies in HIV care for over a decade" said University of Washington's Dr. Mari Kitahata, the lead researcher on the study. "Our study adds weight to the growing body of evidence that starting treatment earlier in HIV disease saves lives."
Current U.S. guidelines recommend treatment for asymptomatic patients who have a CD4 count of less than 350. However, these guidelines lack data from randomized clinical trials regarding the timing of antiretroviral therapy.
Since 1996, when potent antiretroviral therapy was introduced and recommended for asymptomatic HIV patients with a CD4 count less than 500 cells per cubic millimeter, there has been uncertainty about when to start treatment.
Almost 18,000 people studied
The article reports on two analyses of 17,517 asymptomatic patients with HIV infection receiving care between 1996 and 2006. The data were gathered through a recent collaboration of 22 research groups in more than 60 sites in the United States and Canada -- the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
In order to study the impact of earlier initiation of therapy, researchers needed such a large number of patients at high CD4+ counts who are observed for a long period of time to a definitive endpoint of death. Because of the combined effort of one of the largest collaborations of HIV cohorts in the world, researchers had enough data to examine the effect of early HIV treatment.
study 1 - wait until CD4 falls below 350
Results from the first analysis were announced Oct. 2008 . Among the 8,632 patients with a CD4+ count+ 351 to 500, those who deferred antiretroviral therapy until the CD4+ count was below 350 had an increase of 69% in the risk of death.
study 2 - wait until CD4 falls below 500
Results from the second analysis were announced Feb 2009. Among the 9,155 patients with a CD4+ count above 500, those who deferred antiretroviral therapy until the CD4+ count was below 500 had an increase of 94% in the risk of death.
Recommendations for when to start antiretroviral therapy from around ten years ago used to delay the start of treatment until much later (a CD4 of 200) to avoid the development of drug resistance and because of significant side effects. Now treatment is much easier, drug resistance is of less concern, side effects are much reduced and better managed, and the evidence is that it makes much more sense to start therapy even earlier.
Benefits of earlier therapy are that immune system functioning is far better preserved, and you are more likely to get close to a normal CD4 count again, you become barely infectious and you can expect a near normal lifespan.
Mari Kitahata says "For years, we have started patients on HIV therapy when their immune systems were already compromised. It is becoming clear that early institution of antiretroviral therapy, before the immune system is heavily damaged, saves lives."
New England Journal of Medicine article
NEJM Editorial
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