When to start antiretroviral therapy.

The question of when to initiate antiretroviral therapy has been a central controversy in HIV management for more than 15 years, yet there are limited data from randomized controlled trials addressing it. A major obstacle to performing such a study is the need for large numbers of asymptomatic, antiretroviral therapy-naive individuals observed over many years beginning from when their CD4+ cell counts are above 500/mm3. Observational cohort studies with substantial person-years of follow-up have informed this debate in the absence of randomized trials. Emerging evidence regarding the damage caused by untreated HIV infection-related inflammation and immune activation at all stages of disease, and the benefits of modern antiretroviral therapy in preventing both AIDS- and non-AIDS-related morbidity and mortality has supported a return to starting treatment early. The NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) study compared long-term outcomes of immediate versus deferred therapy at 2 CD4+ cell count thresholds. Results showed a 94% increased risk of all-cause mortality when antiretroviral therapy was deferred at CD4+ cell counts greater than 500/mm3. This article summarizes presentations made by Mari M. Kitahata, MD, MPH, at the International AIDS Society-USA continuing medical education programs held in November 2009 in New York City and May 2010 in San Francisco. The original presentations are available as Webcasts at www.iasusa.org.