Treating HIV-infected infants early helps them live longer

[Guest guest]

Treating HIV-Infected Infants Early Helps Them Live LongerSouth 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 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 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.

http://www.nih.gov/news/pr/jul2007/niaid-25.htm

Kumara Singaravelu, M.B.B.S., M.P.H

School of Public Health

State University of New York - Albany.

e-mail: <kcvel@...>