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CROI 2012: Infants with HIV Who Receive Early ART Can Safely Stop Treatment

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HIV-infected infants who start antiretroviral therapy (ART) immediately after birth can interrupt treatment after 1-2 years and still do better than babies who delayed ART initiation until they developed symptoms, researchers reported at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this month in Seattle.

A related study found that among children older than 1 year who were not diagnosed as HIV-infected HIV at birth, those who started ART at the time of diagnosis and those who waited until they showed symptoms had similar rates of neurocognitive and behavior problems, but both groups were at higher risk than children who were diagnosed and started therapy soon after birth.

Below is an edited excerpt from a media announcement issued by the National Institutes of Health, which funded the CHER and PREDICT studies, describing the findings presented at CROI.

NIH-Funded Studies Show Benefits of Immediate Antiretroviral Treatment for HIV-Infected Infants

March 6, 2012 -- Results from two studies presented today at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle demonstrate the importance of identifying and treating HIV-infected infants within the first year of life both to prevent harm to the immune system and to enable normal neurological development.

Although immediate ART during infancy benefits HIV-infected babies, the prospect of lifelong treatment raises numerous concerns, including the risk of drug side effects and the potential for resistance to develop to available treatments.

The "Children with HIV Early Antiretroviral Therapy" (CHER) trial, funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, launched in South Africa in 2005. It tested a novel strategy of giving immediate ART to HIV-infected infants (babies under 3 months of age) but stopping it after the period of infancy when the risks of consequences from HIV and other infections decreases. Treatment was not resumed until there was some evidence of health decline.

The study initially compared immediate versus delayed treatment, but the delayed treatment arm was stopped in 2007 after a data and safety monitoring board found that infants given ART beginning at an average age of 7 weeks had a significantly lower risk of death within 48 weeks compared with infants in the deferred treatment group. Based on these findings, in 2008 the World Health Organization revised its treatment guidelines to recommend that in HIV-infected children under the age of one, ART be started immediately after HIV diagnosis, regardless of their state of health.

Study results presented [March 6] by Mark Cotton, MD, PhD, of Stellenbosch University in South Africa, showed that infants could safely stop ART after 1 to 2 years and continue to fare significantly better than those infants in whom the initiation of therapy was delayed until signs of illness or a weakened immune system appeared. Importantly, very few infants who received immediate ART had significant disease progression or died after treatment was stopped. Many of the infants who stopped therapy were able to remain off treatment for a long time. In follow up of the 375 study participants, 33 percent of infants who received 2 years of initial ART and 25 percent of the infants who received 1 year of initial therapy were still well and, therefore, able to remain off treatment for roughly 5 years after the study officially ended.

Another presentation highlighted new results from the PREDICT [Pediatric Randomized Early vs. Deferred Initiation in Cambodia and Thailand] study. This Phase III clinical trial among HIV-infected children in Thailand and Cambodia examined the question of when to begin ART in children who were not diagnosed with HIV during infancy and, therefore, did not present for medical treatment until they became mild to moderately sick.

The study, which began in 2006 and involved 299 children ages 2 to 12, compared beginning treatment immediately or delaying treatment until levels of CD4+ T cells, a key indication of immune system health, fell to a certain threshold.

Jintanat Ananworanich, MD, PhD, of the HIVNAT Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, presented findings at CROI today demonstrating that both study groups experienced comparably low rates of disease progression, while higher rates of drug toxicities and resistance were found in the immediate treatment group. Neurological development problems were frequent and equally prevalent in both groups.

Taken together, both the CHER and PREDICT studies illustrate the importance of identifying and treating HIV-infected infants as soon as possible to preserve the immune system and ensure healthy brain development. If the treatment in infancy window is missed, ART in older HIV-infected children, whether begun immediately or delayed, can still provide comparable health benefits but it does not prevent or reverse neurological damage.

The PREDICT study was sponsored by NIAID, with further neurological analysis of the study participants supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, also part of the NIH.

3/9/12

References

M Cotton, A Violari, D Gibb, et al. Early ART followed by Interruption Is Safe and Is Associated with Better Outcomes than Deferred ART in HIV+ Infants: Final Results from the 6-Year Randomized CHER Trial, South Africa. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 28LB.

T Puthanakit, J Ananworanich, S Vonthanak, et al. Neurodevelopmental Outcome among HIV+ Children >1 Year of Age Randomized to Immediate vs Deferred ART: The PREDICT Study (NCT00234091). 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 24.

Other Sources

National Institutes of Health. NIH-Funded Studies Show Benefits of Immediate Antiretroviral Treatment for HIV-Infected Infants. Press release. March 6, 2012.

National Institute of Mental Health. NIH-funded study defines treatment window for HIV-positive children infected at birth. Press release. March 7, 2012.