July 20, 2015
Updated July 20, 2015
The START (“Strategic Timing of AntiRetroviral Treatment”) study is a randomized, controlled clinical trial designed to more clearly define the optimal time for HIV- infected individuals to begin antiretroviral therapy. The trial enrolled healthy, asymptomatic, HIV-infected people whose level of CD4+ T cells—a measure of immune system health—exceeded 500 cells per cubic millimeter (mm3). The primary objective was to determine whether taking antiretroviral therapy immediately would lead to a lower risk of AIDS, other serious illnesses or death compared to waiting until a person’s CD4+ T-cell count fell to 350 cells/mm3.
The study is conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), which is led by principal investigator James D. Neaton, Ph.D., of the University of Minnesota. INSIGHT is funded by the National Institute of Allergy and Infectious Diseases (NIAID). The START protocol co-chairs are Abdel Babiker, Ph.D., of the Medical Research Council Clinical Trials Unit, London; Fred Gordin, M.D., of the Veterans Affairs Medical Center, Washington, D.C.; and Jens Lundgren, M.D., D.M.Sc., of the Copenhagen HIV Program.
The University of Minnesota sponsored the study and worked closely with four international coordinating centers to implement and oversee the conduct of the trial. These coordinating centers were the Copenhagen HIV Program at the Rigshospitalet, University of Copenhagen, Denmark; the Kirby Institute at the University of New South Wales in Sydney; The Medical Research Council Clinical Trials Unit at University College London; and the Washington, D.C. Veterans Affairs Medical Center affiliated with The George Washington University in Washington, D.C.
The START study was conducted at 215 sites in 35 countries: Argentina, Australia, Austria, Belgium, Brazil, Chile, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Luxembourg, Malaysia, Mali, Mexico, Morocco, Nigeria, Norway, Peru, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, Thailand, Uganda, the United Kingdom and the United States (including Puerto Rico).
The START trial enrolled 4,685 HIV-infected men and women ages 18 years or older (median age of 36 years) who had CD4+ T-cell counts above 500 cells/mm3, no symptoms of HIV infection, and had never taken antiretroviral therapy. Twenty-seven percent of the participants are women, and approximately half are gay men.
The first participant was enrolled in April 2009, during the study’s pilot phase. The main study began in March 2011 and was scheduled to end in December 2016.
Study participants were randomly assigned to either begin antiretroviral treatment immediately or delay starting treatment until either their CD4+ T-cell counts dropped to 350 cells/mm3 or they were diagnosed with an AIDS-defining illness.
A data and safety monitoring board (DSMB) is an independent group composed of clinical research experts, statisticians, ethicists and community representatives that meets at regular intervals during a study to review data as it is gathered. Because the study team is blinded to interim study data, they are excluded from portions of meetings when data are presented. The DSMB alerts the study team if anything appears to compromise the safety of study participants, if there is compelling evidence of effectiveness, or if it becomes clear that the study cannot answer one of the questions it was designed to address.
Starting antiretroviral therapy early prevents a combination of outcomes that includes AIDS events (such as AIDS-related cancer) and serious non-AIDS events (major cardiovascular, renal and liver disease, non-AIDS cancer, and death not attributable to AIDS). According to a new analysis of data from the Strategic Timing of AntiRetroviral Treatment (START) study, the first large-scale randomized clinical trial to establish that earlier antiretroviral treatment benefits all HIV-infected individuals, rates of both serious AIDS and serious non-AIDS events were significantly reduced with early therapy. Furthermore, other potentially life threatening events and unscheduled hospitalizations for reasons other than AIDS that were assessed to measure the safety of early treatment did not differ between the immediate and deferred antiretroviral therapy groups.
During a scheduled interim review of study data that had accrued through March 13, 2015, the DSMB found compelling evidence that the benefits of starting antiretroviral treatment immediately at CD4+ cell counts above 500 cells/mm3 outweigh the risks. Specifically, the DSMB found that over an average follow-up of three years, the risk of AIDS, other serious illnesses or death was reduced by 53 percent among those in the early treatment group compared to those in the deferred treatment group. In its review, the DSMB found 41 instances of AIDS, serious non-AIDS illness or death among those enrolled in the study’s early treatment group compared to 86 such events in the deferred treatment group. These results indicate that starting anti-HIV treatment soon after diagnosis of HIV infection protects people’s health. These findings are likely to affect many countries’ guidelines for when to start treatment for HIV infection.
The interim analysis reviewed by the DSMB showed the following:
When the DSMB recommended that early treatment be offered to all study participants, their recommendation was based on data that had accrued through March 13, 2015. The study team was subsequently able to analyze additional data that had been collected through May 26, the day prior to NIAID's public announcement of the DSMB's recommendation. Analysis of this additional data has allowed the study team to draw additional conclusions beyond those reported in May.
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of
infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research,
and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH...Turning Discovery Into Health ®
back to top
Last Updated July 20, 2015
Last Reviewed July 20, 2015