When To Start Therapy for HIV Infection: A Swinging Pendulum in Search of Data

Among the fundamental questions that need to be addressed regarding the treatment of patients with HIV infection are the strategy questions of when to start therapy, what therapy to start, and when to change therapy. The current inability to eradicate HIV, which has led to a need for long-term therapeutic strategies, and the increased recognition of long-term drug toxicities have made these questions compelling. Unfortunately, the answers remain unclear.

Over the past 7 years, in the absence of definitive evidence, several professional societies and governmental entities have provided guidelines for the initiation of antiretroviral therapy (ART). These organizations have suggested guidelines that deal with a wide range of issues—from the treatment of all patients with viral loads greater than 10 000 copies/mL (1) to the more recent recommendation to definitely begin therapy only in patients with CD4⁺ T-cell counts less than 0.200 × 10⁹ cells/L. Guidelines for the best approach to patients with CD4⁺ T-cell counts between 0.200 and 0.350 × 10⁹ cells/L remain uncertain (2). As stated in the most recent edition of the guidelines from the U.S. Department of Health and Human Services and the Henry J. Kaiser Family Foundation (3), “While randomized clinical trials provide strong evidence for treating patients with <200 CD4⁺ T cells/mm³, the optimal time to initiate antiretroviral therapy among asymptomatic patients with CD4^{+ …}