Recent revisions to North American HIV treatment guidelines have taken a more cautious approach to the timing of treatment. This shift was necessary as it became clear that highly active antiretroviral therapy (HAART) has the following limitations:
The question of "when to start" therapy is not easily answered. To try and help find some answers to this question research teams around the globe are observing the effect of anti-HIV therapy in people at different stages of HIV disease.
One study in Italy called ICONA enrolled more than1,400 subjects who had never been exposed to anti-HIV drugs (they were "treatment naive"). The doctors gave them HAART and have been monitoring their progress for at least two years. After analysing their data the doctors found that subjects who started therapy with fewer than 200 CD4+ cells were more likely to eventually develop detectable viral loads than subjects who started therapy with more than 200 CD4+ cells. Importantly, the researchers stated that "there was no clear immunological or virological advantage to starting HAART at a CD4+ cell count higher than 350 cells rather than when the count was between 200 to 350 cells."
Researchers reviewed data collected from 1,421 subjects whose profile at the start of the study was as follows:
After subjects enrolled in the study, here is a profile on their use of HAART:
The ICONA study is ongoing and the results presented here are based on about two years of data collection.
To understand the effects of therapy at different stages HIV infection researchers divided subjects into three groups based on their CD4+ cell counts. The groups were as follows:
On average, regardless of pre-study CD4+ count, CD4+ counts rose by at least 180 extra cells in all groups. This increase was maintained for up to two years after subjects began to use HAART. Despite the use of HAART, about 9% of subjects had a CD4+ count that remained below the 200 cell mark. Researchers aren't sure why this poor immunologic response occurred. They do note that 29 of the 32 subjects who had a poor immunologic response had entered the study with a CD4+ count below the 201 cell mark.
The researchers sought to find out if there was a link between rising viral load and the CD4+ count at the start of the study. They called this rising viral load "virological failure" and defined it as a viral load that was greater than 500 copies after six months of HAART on at least two occasions.
By the 2nd year of the study, the risk of virological failure — which researchers found was linked to the CD4+ count the subjects had at the start of the study — was as follows:
The pre-study viral load did not appear to have any impact on whether or not HAART regimens were able to suppress viral load during the study.
The researchers calculated the risk of subjects developing life-threatening infections (AIDS) or dying, particularly among those subjects who entered the study with fewer than 50 CD4+ cells. They found that the risk of developing AIDS or dying was high at first, but as HAART boosted the CD4+ count, the risk decreased dramatically as follows:
In summarizing their results the researchers reported that there was no evidence that starting therapy when the CD4+ count was greater than 350 cells instead of at a lower level — between 201 and 350 cells — offered any increased immunological benefit two years later.
As the ICONA study continues and data collection increases, further conclusions about the benefits of early vs. late therapy will become available.
REFERENCE
Cozzi Lepri A, Phillips AN, Monforte A d'A, et al. When to start highly active antiretroviral therapy (HAART) in chronically HIV-infected patients: evidence from the ICONA study. AIDS 2001;15(8):983-990.
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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