Starting Antiretroviral Treatment Early Improves Outcomes for HIV-Infected Individuals
NIH-Funded Trial Results Likely Will Impact Global Treatment Guidelines
May 27, 2015 - A major international randomized clinical trial has found that HIV-infected individuals have a
considerably lower risk of developing AIDS or other serious illnesses if they start taking
antiretroviral drugs sooner, when their CD4+ T-cell count—a key measure of immune system
health—is higher, instead of waiting until the CD4+ cell count drops to lower levels.
Together with data from previous studies showing that antiretroviral treatment
reduced the risk of HIV transmission to uninfected sexual partners, these
findings support offering treatment to everyone with HIV.
The new finding is 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. The National Institute of Allergy and Infectious Diseases (NIAID), part
of the National Institutes of Health, provided primary funding for the START trial. Though the
study was expected to conclude at the end of 2016, an interim review of the study data by an
independent data and safety monitoring board (DSMB) recommended that results be released early.
“We now have clear-cut proof that it is of significantly greater health benefit to an HIV-infected
person to start antiretroviral therapy sooner rather than later,” said NIAID Director Anthony S. Fauci, M.D.
“Moreover, early therapy conveys a double benefit, not only improving the health of individuals but
at the same time, by lowering their viral load, reducing the risk they will transmit HIV to others.
These findings have global implications for the treatment of HIV.”
“This is an important milestone in HIV research,” said Jens Lundgren, M.D., of the University of
Copenhagen and one of the co-chairs of the START study. “We now have strong evidence that early
treatment is beneficial to the HIV-positive person. These results support treating everyone
irrespective of CD4+ T-cell count.”
The START study, which opened widely in March 2011, was conducted by the International Network for
Strategic Initiatives in Global HIV Trials (INSIGHT) at 215 sites in 35 countries. The trial
enrolled 4,685 HIV-infected men and women ages 18 and older, with a median age of 36.
Participants had never taken antiretroviral therapy and were enrolled with CD4+
cell counts in the normal range—above 500 cells per cubic millimeter
(cells/mm3). Approximately half of the study participants were
randomized to initiate antiretroviral treatment immediately
(early treatment), and the other half were randomized
to defer treatment until their CD4+ cell count declined to 350 cells/mm3. On average, participants
in the study were followed for three years.
The study measured a combination of outcomes that included serious AIDS events (such as AIDS-related
cancer), serious non-AIDS events (major cardiovascular, renal and liver disease and cancer), and death.
Based on data from March 2015, the DSMB found 41 instances of AIDS, serious non-AIDS events or death
among those enrolled in the study’s early treatment group compared to 86 events in the deferred treatment group. The DSMB’s interim analysis found risk of developing serious illness or death was reduced by 53 percent among those in the early treatment group, compared to those in the deferred group.
Rates of serious AIDS-related events and serious non-AIDS-related events were both lower in the
early treatment group than the deferred treatment group. The risk reduction was more pronounced
for the AIDS-related events. Findings were consistent across geographic regions, and the
benefits of early treatment were similar for participants from low- and middle-income
countries and participants from high-income countries.
“The study was rigorous and the results are clear,” said INSIGHT principal investigator James D. Neaton,
Ph.D., a professor of biostatistics at the University of Minnesota, Minneapolis. “The definitive findings
from a randomized trial like START are likely to influence how care is delivered to millions of
HIV-positive individuals around the world.” The University of Minnesota served as the trial’s
regulatory sponsor and statistical and data management center.
Prior to the START trial, there was no randomized controlled trial evidence to guide initiating
treatment for individuals with higher CD4+ cell counts. Previous evidence to support early
treatment among HIV-positive people with CD4+ cell counts above 350 was limited to data
from non-randomized trials or observational cohort studies, and on expert opinion.
START is the first large-scale randomized clinical trial to offer concrete scientific evidence to
support the current U.S. HIV treatment guidelines, which recommend that all asymptomatic HIV-infected individuals take antiretrovirals, regardless of CD4+ cell count. Current World Health Organization HIV treatment guidelines recommend that HIV-infected individuals begin antiretroviral therapy when CD4+ cell counts fall to 500 cells/mm3 or less.
In light of the DSMB findings, study investigators are informing all participants of the interim
results. Participants will be offered treatment if they are not already on antiretroviral therapy,
and they will continue to be followed through 2016.
The HIV medicines used in the trial are approved medications donated by AbbVie, Inc., Bristol-Myers
Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and
Merck Sharp & Dohme Corp.
In addition to NIAID, funding for the START trial came from other NIH entities, including the National
Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Mental Health;
the National Institute of Neurological Disorders and Stroke; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the NIH Clinical Center; and the National
Institute of Arthritis and Musculoskeletal and Skin Diseases. Funding was also provided
by the National Agency for Research on AIDS and Viral Hepatitis (ANRS) in France,
the Federal Ministry of Education and Research in Germany, the European AIDS
Treatment Network and government organizations based in Australia, Denmark, and the United Kingdom.
The Medical Research Council Clinical Trials Unit at University College London; the Copenhagen HIV Program
at the Rigshospitalet, University of Copenhagen in Denmark; the Kirby Institute at the University of New
South Wales in Sydney, Australia; and the Veterans Affairs Medical Center affiliated with George
Washington University in Washington, D.C. coordinated the work of the 215 START sites.
For more information about the START trial, see the Questions and Answers or
visit ClinicalTrials.gov using study identifier NCT00867048 .
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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.
Source: National Institute of Allergy and Infectious Diseases (NIAID) http://www.niaid.nih.gov/news/newsreleases/2015/Pages/START.aspx#
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