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Revisions to the April 8, 2015, version of the guidelines are largely based on findings from two large, randomized controlled trials that addressed the optimal time to initiate antiretroviral therapy (ART)—START (Strategic Timing of Antiretroviral Therapy) and TEMPRANO. Both studies demonstrated approximately a 50% reduction in morbidity and mortality among HIV-infected individuals with CD4 T lymphocyte cell (CD4) counts >500 cells/mm3 randomized to receive antiretroviral therapy (ART) immediately versus delaying initiation of ART. Key updates related to these studies and other significant changes are highlighted throughout the guidelines.