Landmark Study Defines Benefits of Early
HIV Testing and Treatment for Infected Infants
Testing very young babies for HIV and giving antiretroviral therapy
(ART) immediately to those found infected with the virus dramatically
prevents illness and death, according to a report in the New
England Journal of Medicine. The study found that giving ART
to HIV-infected infants beginning at an average age of 7 weeks
made them four times less likely to die in the next 48 weeks, compared
with postponing ART until signs of illness or a weakened immune
system appeared — the standard of care when the study began.
These findings come from the "Children with HIV Early Antiretroviral
Therapy" (CHER) study, the first Phase III randomized clinical
trial to study the best time to begin ART in infants. Launched
in South Africa in July 2005, CHER is sponsored by the National
Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health, and the departments of health of
the Western Cape and Gauteng in South Africa.
"HIV devastates the nascent immune systems of infants very
quickly, yet too many HIV-infected infants do not get tested for
the virus, get tested too late or get tested but lack access to
lifesaving antiretroviral drugs," says Anthony S. Fauci, M.D.,
the director of NIAID. "The results of CHER are a clarion
call to scale up widespread early HIV testing of at-risk infants
and to make ART immediately accessible to all infants who test
Preliminary results of CHER, released in July 2007, showed that
HIV-infected infants were four times less likely to die if given
ART immediately after HIV diagnosis (http://www3.niaid.nih.gov/news/newsreleases/2007/cher.htm).
This finding helped influence the World Health Organization (WHO)
to change its guidelines for treating HIV-infected infants. The
new guidelines, issued in April 2008, strongly recommend starting
ART in children under age 1 immediately after HIV diagnosis, regardless
of their state of health. An NIAID study to identify the best drug
regimen for these highly vulnerable children is under way.
"The new WHO guidelines will profoundly improve the survival
rate and quality of life of infants born with HIV," says Ed
Handelsman, M.D., chief of the Pediatric Medicine Branch in NIAIDís
Division of AIDS. "We are excited that we know the best time
to begin treating HIV-infected infants; the challenge now for the
global community is to ensure that all HIV-infected infants who
need ART receive it soon enough."
The CHER study team, lead by Avy Violari, FCPaed, and Mark F.
Cotton, MMed PhD, recruited and enrolled 377 infants between 6
and 12 weeks of age who had confirmed HIV infection but normal
immune system development. Originally, the infants were randomly
assigned to one of three regimens: start ART immediately and continue
for 40 weeks; start ART immediately and continue for 96 weeks;
or defer ART until signs of clinical or immunological progression
to AIDS appeared. The ART regimen consists of ritonavir-boosted
lopinavir, zidovudine and lamivudine, provided by GlaxoSmithKline
PLC of Britain and the South African Department of Health. CHER
is being conducted at two locations in South Africa: the Perinatal
HIV Research Unit of the University of Witwatersrand; and the Childrenís
Infectious Diseases Clinical Research Unit of Tygerberg Childrenís
Hospital and Stellenbosch University. These sites are collaborating
with the Medical Research Council Clinical Trials Unit in London.
In June 2007, a data and safety monitoring board (DSMB) overseeing
CHER found that the babies who received immediate ART were four
times less likely to die than the babies whose treatment was deferred.
This was true even though 66 percent of those in the deferred treatment
arm had met the criteria for ART during the first 32 weeks of the
trial and already had begun treatment. Consequently, the DSMB recommended,
and NIAID agreed, to assess all the children in the deferred-treatment
arm for potential initiation of ART.
The study measured the effectiveness of the treatment strategies
by counting the number of babies who died or whose immune systems
were not protected by the original ART regimen. After a median
of 48 weeks, 10 of 252 infants (4 percent) in the immediate-treatment
arms had died, as had 20 of 125 (16 percent) infants in the deferred-treatment
arm. Thus, immediate ART reduced deaths by 75 percent. As a secondary
measure of success or failure, CHER counted the number of infants
who developed HIV-related disease. Such disease developed in 16
babies (6.3 percent) in the immediate-treatment arms and 32 babies
(26 percent) in the deferred-treatment arm. Thus, the infants who
received treatment immediately were more than four times less likely
to develop HIV-related disease.
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 http://www.niaid.nih.gov.
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.
A Violari et al. Early antiretroviral therapy reduces mortality in
HIV-infected infants: evidence from the CHER trial. New England
Journal of Medicine DOI 10.1056/NEJMoa0800971 (2008).