Emma Hitt, PhD

July 20, 2011

July 20, 2011 (Rome, Italy) — Immediate antiretroviral therapy (ART) initiation in children of at least 1 year of age with HIV infection and moderate immunodeficiency did not significantly increase AIDS-free survival or improve neurodevelopmental outcome compared with when ART initiation was deferred until the child had a CD4 cell count lower than 15%, suggest new findings from 144 weeks of follow-up of the PREDICT study.

Thanyawee Puthanakit, MD, from the Thai Red Cross AIDS Research Center in Bangkok, Thailand, and colleagues presented the findings here at the 6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, during a late-breaking poster session.

Dr. Thanyawee Puthanakit

"The results from the PREDICT study suggest that HIV-infected children who survive their first year of life without [ART] have slow disease progression to AIDS," Dr. Puthanakit told Medscape Medical News at the meeting.

The PREDICT study included 300 children aged 1 to 12 years with CD4 counts between 15% and 24%. Participants were randomly assigned to receive ART initiated either at enrollment (immediate; n = 150) or when CD4 count fell below 15% or CDC category C events developed (delayed; n = 150).

The researchers found that during approximately 3 years of follow-up, only 5 CDC category C (or AIDS) events developed among the 300 HIV-infected children in the study. AIDS-free survival among HIV-infected children aged 1 to 12 years who started ART at CD4 cell counts between 15% and 24% was 98% compared with 99% among children who were closely monitored for CD4 levels every 3 months and who started ART when CD4 fell below 15% (delayed).

According to Dr. Puthanakit, the PREDICT study found different results than the Children with HIV Early Antiretroviral Therapy trial, which showed that initiating ART before 3 months of age significantly improved survival. "The differences could be explained by a bimodal disease progression in HIV-infected children," she said. "About 20% of children seem to have a rapid disease progression during the first year of life, while the rest have slower disease progression."

Dr. Puthanakit noted that because of limited access to early infant diagnosis with HIV polymerase chain reaction testing, the majority of HIV-infected infants in resource-limited settings are not diagnosed during the first year of life.

"Close CD4 monitoring every 3 months and starting lifelong therapy when CD4 counts drop below 15% can be an option for circumstances when initiating ART immediately is not feasible," she said. "Furthermore, the difficulty of accurately administering the right dose to young children both increases the risk of either overdosing, leading to toxicity, or underdosing, leading to potential drug resistance," she said. "For this reason there may be an advantage in delaying treatment, when possible, until children whose disease is progressing slowly are older."

Independent commentator Paul E. Palumbo, MD, professor of medicine and pediatrics and director of the International Pediatric HIV program at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, noted that these are "much-awaited data, which reintroduced and reinforces the concept of observing children who are doing well with deferred therapy."

"The results need to be interpreted with caution since the study is small and ideally would benefit from confirmation by another cohort," he told Medscape Medical News. "However, the current cohort has a full 3 years of follow-up, the study is ongoing, and overall it opens the door for consideration of deferred pediatric therapy in controlled settings" he pointed out.

The study was not commercially funded. Drugs were supplied by multiple commercial sources. Dr. Puthanakit and Dr. Palumbo have disclosed no relevant financial relationships.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TULBPE023. Presented July 19, 2011.


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