How have guidelines on when to start antiretroviral therapy affected survival of people living with HIV infection?

Abstract

Until recently, conflicting data led to discrepancies in guideline recommendation on 'when to start' antiretroviral therapy (ART) in asymptomatic HIV infection. This review focuses on evidence underpinning guidelines over the past decade and recent randomized clinical trial data in this area, which definitively informed the debate. In 2015, the landmark START trial demonstrated clear clinical benefit in terms of a reduction in serious AIDS and non-AIDS-related events and death from any cause in HIV-positive individuals randomized to start ART with a CD4 count more than 500 cells/μl compared with deferring starting until CD4 count declined to 350 cells/μl. Further, randomized clinical trial data were also available from the Temprano trial in Côte D'Ivoire which also demonstrated a reduced risk of death associated with earlier ART initiation. Following the results of the START trial, guidelines that had previously set CD4 thresholds for treatment initiation were universally changed. This is likely to reduce mortality in people living with HIV who are diagnosed early and have immediate access to ART. However, unless HIV testing rates and ART coverage are increased globally, raising the threshold for initiation of ART in clinical guidelines may be of limited benefit in reducing mortality in HIV.