NIH
Study Examines Best Time for Healthy
HIV-infected People to Begin Antiretrovirals
A
major new clinical trial seeks to determine whether HIV-infected
asymptomatic individuals have less risk of developing AIDS
or other serious illness if they begin taking antiretrovirals
sooner rather than later, based on their level of CD4+ T-cells.
An HIV-infected individual's level of CD4+ T-cells -- commonly
referred to as their CD4 count -- is a key measure of immune
system health. The study is co-funded by the National Institute
of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health.
While data from randomized clinical trials exist to support
starting antiretroviral treatment when CD4 counts fall below
350 cells per cubic millimeter (mm3), well-designed clinical
trials have not been conducted to guide decisions to support
starting treatment above that threshold. As a consequence,
guidelines differ with regard to if and when to begin antiretroviral
treatment in asymptomatic HIV-infected individuals with
CD4 counts above 350 cells/mm3. Current U.S. guidelines
recommend that these individuals should begin antiretrovirals
when their CD4 counts fall below 500 cells/mm3, whereas
the World Health Organization recommends this group start
treatment only when their CD4 count falls to or below the
350 cells/mm3 cutoff.
The new Phase IV study, known as the Strategic Timing of
Antiretroviral Treatment (START) clinical trial, is a randomized
clinical trial designed to provide definitive evidence of
the risks and benefits of early antiretroviral treatment
to more clearly define the optimal time to begin medication.
It seeks to determine if immediate antiretroviral therapy
among HIV-infected individuals with CD4 levels above 500
cells/mm3 is better than deferring treatment until CD4 counts
fall below 350 in terms of potential benefits and risks,
such as developing AIDS and other serious illnesses, including
cardiovascular disease, cancer, kidney failure, and liver
disease, or death. The launch of the START trial follows
the successful completion of a pilot study involving more
than 1,000 participants.
"Some epidemiological evidence suggests that HIV-infected
patients remain healthier when they begin treatment at higher
CD4 counts. However, there are also concerns about the health
complications and side effects associated with lifelong
antiretroviral use and the possibility that the virus may
become resistant to medication," says NIAID Director
Anthony S. Fauci, MD. "The START trial will provide
a more clear-cut answer as to the best time for HIV patients
to begin treatment, taking into account both the risks and
benefits associated with early versus deferred treatment."
START will be conducted in 30 countries. It will enroll
4,000 HIV-infected men and women 18 years of age and older
who have CD4 counts above 500 cells/mm3 and who have never
taken antiretroviral therapy. Once entered into the study,
half of the participants will be assigned randomly to receive
immediate antiretroviral therapy. The other half of the
study group will not receive antiretroviral therapy until
their CD4 counts fall below 350 cells/mm3 or an AIDS-related
event occurs.
Study clinicians will select the appropriate antiretroviral
regimen for each participant from a pre-approved list based
on U.S. Department of Health and Human Services treatment
guidelines. The HIV medicines being used in the trial are
approved medications donated by Abbott Laboratories, Bristol-Myers
Squibb, Gilead Sciences, GlaxoSmithKline, Merck & Co.
and Tibotec Pharmaceuticals.
Participants will be followed for up to five years. Once
enrolled, they will return to the clinic to be seen by study
staff at one month, four months and then every four months
thereafter. At each visit, participants will provide a medical
update and undergo a brief medical exam, and CD4 cell counts
and viral load (the amount of HIV in the blood) will be
recorded.
The study is being conducted by the International Network
for Strategic Initiatives in Global HIV Trials (INSIGHT),
an HIV/AIDS clinical trial network funded by NIAID. The
University of Minnesota in Minneapolis is the trial sponsor
with primary funding from NIAID and additional funding provided
by 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, and the National Institute of Arthritis
and Musculoskeletal and Skin Diseases. Additional support
comes from four government organizations based in Australia,
France, Germany, and the United Kingdom.
Although START will primarily look at major health outcomes
associated with immediate and deferred antiretroviral therapy,
the study will also examine HIV transmission risk behaviors,
treatment adherence, drug resistance, health care utilization
and the cost of care. "The intent is to fully evaluate
the individual and the broader public health implications
of earlier antiretroviral treatment," according to
James D. Neaton, PhD, of the University of Minnesota, principal
investigator for INSIGHT.
START will also feature several sub-studies to be conducted
across some of the 200 study sites. These sub-studies include
examining the effect of genetic variants of the virus on
the progression of untreated HIV, as well as the response
of patients to antiretroviral therapy; comparing the early
and deferred antiretroviral groups for neurocognitive function
and measures of vascular function, pulmonary function, and
bone mineral density; and evaluating participant understanding
of study information and satisfaction with the consent process
to better inform future research guidelines.
START is identified on www.clinicaltrials.gov
as NCT00867048.
For more information about NIAID's HIV/AIDS research, go
to: www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx.
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 Web site at www.niaid.nih.gov.
The National Institutes of Health (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. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and
cures for both common and rare diseases. For more information
about NIH and its programs, visit www.nih.gov.
