Strong evidence from randomised trials did not exist to guide decisions about the initiation of highly active ART regimens for HIV-infected individuals with CD4+ cell counts > 200 cells. Guidelines were based largely on data from observational studies.
The purpose of this randomised study was to determine whether immediate initiation of antiretroviral treatment (ART) was superior to deferral of ART until the CD4+ declines below 350 cells in terms of morbidity and mortality in HIV-1 infected persons who are antiretroviral naïve with a CD4+ count above 500 cells.
START is an international randomised trial comparing early ART versus deferred ART. Participants were randomised in a 1:1 allocation ratio to the early or deferred ART group. The primary composite endpoint is the development of a serious AIDS event (“AIDS*”), a serious non-AIDS event (“non-AIDS”), or death from any cause. The study is being conducted at 237 sites in 35 countries. Global enrolment closed with 4,688 participants enrolled.
On May 15, 2015 the independent Data and Safety Monitoring Board (DSMB) for START determined that this question had been addressed. Immediate use of ART provided significant benefit over deferred ART for the primary composite endpoint of START and its two major components, serious AIDS and serious non-AIDS events over an average follow-up of 3 years.
The DSMB recommended offering ART to participants in the deferred arm who had not yet started ART. They also recommended continued follow-up of study participants.
Even though the findings from START unequivocally indicate that immediate ART has substantial benefits on major clinical outcomes compared to deferred ART, longer follow-up, as recommended by the DSMB, is warranted for several scientific and practical reasons. The primary composite endpoint: the development of a serious AIDS event (“AIDS*”), a serious non-AIDS event (“non-AIDS”), or death from any cause will remain the primary focus of the extended follow-up.
- Agence Nationale de Recherche sur le SIDA (ANRS)
- Bristol-Myers Squibb
- Division of Clinical Research, NIAID, NIH
- German Federal Ministry of Education and Research
- Gilead Sciences
- Merck Sharp & Dohme
- National Cancer Institute (NCI)
- National Health and Medical Research Council (NHMRC)
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institute of Mental Health (NIMH)
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Institutes of Health Clinical Center (CC)
- NEAT – European AIDS Treatment Network
- Tibotec Pharmaceutical Limited
- Copenhagen HIV Programme (CHIP) – Copenhagen, Denmark
- Medical Research Council (MRC) Clinical Trials Unit – London, United Kingdom
- The Institute for Clinical Research at the Veterans Affairs Medical Center – Washington, D.C., USA
- University of Minnesota – Clinical and Translational Science Institute – Minnesota, USA