Treating HIV-Infected Infants Early Helps
Them Live Longer
South African Clinical Trial Modified
Because of Initial Data
Hundreds of thousands of babies around the world are born each
year with HIV — more than half a million in 2006 alone. Caring
for these children is complicated by the fact that their immune
systems are not fully developed in the first year of life, which
makes them especially susceptible to rapid HIV disease progression
and death. The current standard of HIV care in many parts of the
world is to treat infants with antiretroviral therapy — but
only after they show signs of illness or a weakened immune system.
Now the initial results of an ongoing clinical trial sponsored
by the National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health (NIH), suggests that
more HIV-infected infants survive if they are given therapy early
on, regardless of their apparent state of health.
This trial, called the “Children with HIV Early Antiretroviral
Therapy” (CHER) study, is a phase III, randomized clinical trial
led by Avy Violari, M.D., FCPaed (SA), of the University of the
Witwatersrand in Johannesburg, South Africa, and Mark Cotton, MBChB,
MMed, of the University of Stellenbosch in Cape Town, South Africa.
Dr. Violari will present these findings on Wednesday, July 25 at
the 2007 International AIDS Society Conference in Sydney, Australia.
“Children with HIV infection frequently show rapid disease progression
within the first year of life due to their developing immune systems
and susceptibility to other serious infections,” says NIH Director
Elias A. Zerhouni, M.D. “This is the first randomized clinical
trial that shows that infants treated before three months of age
will do better than infants who have their treatment delayed.”
“The results of this trial could have significant public health
implications worldwide,” says NIAID Director Anthony S. Fauci,
M.D. “Because these findings will cause experts to consider changes
in standards of care in many parts of the world, NIAID has released
details of the interim results to the World Health Organization,
local ethics committees, regulatory authorities and other key stakeholders
for their consideration and evaluation for possible implementation.”
These initial results also highlight the importance of diagnosing
HIV infections early — within the first six to twelve weeks
of life,” says Edward Handelsman, M.D., chief of the Pediatric
Medicine Branch in NIAID’s Division of AIDS, which is overseeing
the CHER study. Dr. Handelsman stresses, however, that the study
results cannot necessarily be generalized to asymptomatic adults
or older children because young infants are very different in immune
function, time since HIV infection and susceptibility to other
serious illnesses.
The evidence came to light last month after a routine review by
the trial’s data and safety monitoring board (DSMB), an independent
committee composed of clinical research experts, statisticians,
ethicists and community representatives from Africa, Europe and
the United States that regularly reviews interim data from the
CHER study to ensure the safety of study participants.
CHER had begun two years earlier to evaluate whether early antiretroviral
therapy given over a limited period of time would delay disease
progression. The idea was that this approach might allow the immune
system to develop and possibly allow the child to stop treatment
for a period of time and therefore avoid continuous therapy from
an early age.
Starting in July 2005, HIV-infected infants between 6 and 12 weeks
old without immune suppression or severe symptoms of clinical disease
were enrolled at the Perinatal HIV Research Unit in Soweto and
Tygerberg Children’s Hospital in Cape Town. By early 2007, 377
babies were enrolled in one of three groups — those receiving
immediate antiretroviral therapy for 40 weeks, those receiving
immediate antiretroviral therapy for 96 weeks, and a control group
whose treatment was initiated after doctors observed signs of clinical
or immunological progression toward the development of AIDS (the
current standard of HIV care in many parts of the world).
The trial is designed to continue through 2011, but after reviewing
early trial data on June 20, 2007, the DSMB found a significant
increase in survival among infants who received immediate antiretroviral
therapy. At the time of the DSMB review, 96 percent of these children
were alive, compared to only 84 percent of the children in the
control group. Based on this finding, the DSMB concluded that providing
early antiretroviral therapy to infants is more effective in preventing
early death than delaying treatment until clinical or immunological
disease triggers are observed.
The DSMB recommended that no additional infants be placed in the
deferred-treatment arm of the study and infants previously enrolled
in this arm be evaluated for potential initiation of antiretroviral
therapy. NIAID accepted these recommendations and informed the
study investigators at each site. The doctors at those sites have
been contacting the parents and legal guardians of the infants
involved in the study to inform them of the interim findings and
call them in for evaluation. The DSMB also recommended that all
infants enrolled in the study be followed for the planned duration
of approximately 3.5 years and those in the 40- and 96-week treatment
groups continue with the study.
For more information about the CHER study, see http://www3.niaid.nih.gov/news/QA/cher_qa.htm.
NIAID is sponsoring the CHER trial through the Comprehensive International
Program of Research on AIDS (CIPRA) program, which supports research
and development efforts in resource-limited areas to create practical,
affordable and acceptable ways to prevent and treat HIV/AIDS in
adults and children The trial is part of the CIPRA-SA collaborative
research program, led by James McIntyre, MBChB, FRCOG, of the Perinatal
HIV Research Unit, with additional support provided by the MRC
Clinical Trials Unit in London Departments of Health of the Western
Cape and Gauteng, South Africa, and GlaxoSmithKline.
U.S. and International Reporters: Data from the
CHER study will be presented on Wednesday, July 25 at the 2007
International AIDS Society Conference in Sydney, Australia. The
presentation will be at 1:30 p.m. local time in the Bayside Auditorium
B of the Sydney Convention and Exhibition Centre.
The Kaiser Family Foundation will webcast portions of conference,
including the CHER presentation. Reporters should sign up in advance
at www.kaisernetwork.org/ias2007.
NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies. News releases, fact sheets and
other NIAID-related materials are available on the NIAID Web site
at http://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.
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