INSIGHT Strategic Timing of AntiRetroviral Treatment (START) is an international randomized trial to determine whether starting antiretroviral therapy (ART) early (before CD4 drops to less than 500 cells/mm³), rather than waiting until CD4 drops to less than 350 cells/mm³ (when evidence from randomized trials supports starting ART), reduces the occurrence of serious morbidity and mortality. START began enrollment in April 2009 and is currently being carried out at 222 clinics in 35 countries around the world. Enrollment was completed on 23 December 2013, with 4,688 participants.
On 15 May 2015 at a planned interim review, the international Data & Safety Monitoring Board (DSMB) for START unblinded the study team to the results of the trial, notifying the team that the data showed that starting ART while the CD4 is still above 500 cells/mm3 is superior to waiting. The risk of the primary composite endpoint was reduced by more than 50% in people who were randomized to start ART immediately after entering the study. The difference was highly statistically significant. No safety concerns were identified. The DSMB highlighted the excellent conduct of the study. They recommended that follow-up continue and that study participants not yet taking ART be offered the opportunity to start therapy.
At the time START was unblinded, 48% of participants randomized to the deferred arm had begun taking ART. By the end of 2016, 93% of participants in the deferred arm had started ART.
In September 2017, additional funding was awarded to INSIGHT to continue following START participants through 2021. This will allow the study team to determine whether the risk of major morbidity and mortality associated with deferral of ART is eliminated once ART is initiated, or whether it persists due to the lower CD4 cell count at ART initiation.
For a complete list of participating countries and clinics go to the INSIGHT website