IAS: Early Treatment Saves HIV-infected Infants

SYDNEY, July 25 -- Starting antiretroviral therapy in the first 12 weeks of life markedly reduces mortality for infants born with HIV infection.

That message, from a study presented at the International AIDS Society meeting here, could change worldwide treatment guidelines, researchers said.

By starting treatment early, 96% of infants survived the first year of life, Amy Violari, M.D., director of clinical pediatric trials in Soweto, South Africa, reported. But for children for whom treatment was deferred until they showed signs of illness, the one-year survival was 84%.

In the deferred treatment group, there were 20 deaths after 79 person-years of follow-up, compared with 10 deaths in 167 person-years of follow-up in the early treatment group, she said. The difference between the groups reached statistical significance at P=0.0002.

"Starting antiretroviral therapy in children who are born with HIV infection reduces mortality by 75%," Dr. Violari said. "These results support the need for enhanced prophylactic mother-to-child-transmission programs, early infant diagnosis and effective transition to care."

In the CHER (Children with HIV Early Antiretroviral Therapy) trial, doctors recruited 377 children for a three-arm trial. One group of 125 children would not receive treatment until they showed signs of disease or until their CD4-positive count fell below 20%-25% of their total white blood cell count.

In the other two study arms, 252 children were begun on antiretroviral therapy as soon as their HIV status was determined. All of the children were treated with lopinavir/ritonavir, zidovudine, and lamivudine. One group was scheduled to be treated until their first birthday; the second group was to be treated until their second birthday and then drugs would be withdrawn until they became symptomatic. The children would be followed for a minimum of 3.5 years.

The trial was halted early when it became apparent to the trial's data safety and monitoring board that the untreated children were at excess risk of mortality.

"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," said Elias Zerhouni, M.D., director of the National Institutes of Health. The NIH, through the National Institute of Allergy and Infectious Diseases, sponsored the ongoing trial.

Most of the children who died did so within the first three months of life, Dr. Violari reported. Gastroenteritis and sepsis/pneumonia were the main causes of death.

"This is very important data," said Annette Sohn, M.D., of the University of California, San Francisco, who is working on pediatric HIV research in Ho Chi Minh City, Vietnam. "It shows that by withholding treatment from these infants it may be too late to reduce mortality."

However, Dr. Sohn noted, in settings with limited resources, identification of children with HIV often cannot be accomplished until the child actually shows signs of the disease.

"We are dealing with multiple layers of limitation," she said. "The most important limitations are the lack of health care personal, the inability of women in these areas to receive ante-natal care, and laboratory capacity to perform some of these tests."

She said the study may change guidelines on treating infants, but each area will develop its own guidelines based on available resources.