Amanda Mocroft, PhD; Andrew N. Phillips, PhD; Jens D. Lundgren, MD
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Mocroft A., Phillips A., Lundgren J.; HIV Survival Benefit Associated with Earlier Antiviral Therapy. Ann Intern Med. 2004;140:578-579. doi: 10.7326/0003-4819-140-7-200404060-00024
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Published: Ann Intern Med. 2004;140(7):578-579.
TO THE EDITOR:
Palella and colleagues (1) found that initiation of antiretroviral therapy (ART) at CD4+ cell counts of 0.201 to 0.350×109 cells/L was associated with reduced mortality compared with delayed ART. Their study included patients who were followed from 1994 to 2002, so the results partly reflect the era before widespread use of highly active antiretroviral therapy (HAART). We wonder whether calendar year was accounted for in the models and whether restriction of results to patients with time zero after 1996 affected the findings.
Another relevant point is that patients with CD4 cell counts of 0.201 to 0.350×109 cells/L who delayed therapy had a median CD4 cell count of 0.130×109 cells/L when they started ART. This is considerably lower than has ever been recommended (2), and cell counts this low are known to be associated with an increased risk for disease progression (3), making Palella and colleagues' study a comparison between early and very late initiation of ART. It would be interesting to see how the results would have differed if patients who did not start ART were censored when their CD4 cell count fell below 0.200×109 cells/L and if those who never started ART were not excluded. The current relevance of the difference in the percentages of patients with undetectable viral load who were starting and delaying ART is unclear because fewer than 40% of patients had a viral load below the level of detection. This is considerably lower than the levels observed in cohorts that started therapy with HAART (4). In addition, although Palella and colleagues' results were adjusted for receipt of HAART, we were uncertain how this variable was defined because it was unknown at baseline for those who delayed ART. Even if starting HAART at higher CD4 cell counts has a clinical benefit, the reduction in the risk for clinical progression should be weighed carefully against the risks for treatment failure because of problems with long-term adherence, potential toxicities, and the emergence of resistance.
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