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Reviewed by Susa Coffey, MD

Summary

See also Holmberg

The question of when to initiate antiretroviral therapy (ART) in asymptomatic HIV-infected patients continues to be an active topic of debate and discussion. While abundant data demonstrate the importance of initiating ART, if possible, before the CD4 count falls below 200 cells/µL, few data show that patients have better long-term outcomes if treatment is begun at higher CD4 counts. Current U.S. Department of Health and Human Services (DHHS) guidelines recommend starting ART when the CD4 count falls below 350 cells/µL, and certainly before the CD4 count drops below 200 cells/µL. It is not clear, however, whether patients do better in the long term (with less HIV-related morbidity and mortality) if therapy is initiated earlier (at or even above 350 cells/µL) or later, when CD4 count is range of 200 cells/µL.

Because of concern for the significant short- and long-term toxicities of many antiretroviral medications, concern for the possibility of emergent drug resistance, and in the absence of data that demonstrates significantly worse outcomes in patients initiated on therapy at CD4 counts above 200 cells/µL, many clinicians have deferred therapy until later in the course of HIV infection (when the CD4 count approaches 200 cells/µL). However, newer antiretroviral medications that have simpler dosing schedules and perhaps more benign side effect profiles, and fresh insights into mechanisms of HIV-related immune depletion, have provoked reconsideration of our current algorithm.

Comment

Two excellent opinion pieces ( See also Holmberg ) review the data that support earlier vs later initiation of therapy and present lively arguments for and against starting therapy at higher CD4 counts. This piece proposes that "despite recent improvements in HAART, there remain potential disadvantages [to earlier initiation of HAART], including risks of antiretroviral toxicity and emergence of resistance, and, in a field anchored by evidence-based medicine, there is limited evidence of the advantages."