Treat HIV-positive babies from the start

Babies infected with HIV from birth should be given powerful drugs to fight the virus as soon as possible, researchers in South Africa find. In a comparison of treatment strategies, the team reports that babies getting medication, even when they are just weeks old, showed dramatically better survival in subsequent months than those treated only after HIV-related symptoms appeared later. The study appears in the Nov. 20 New England Journal of Medicine.

“I think it’s a landmark trial,” says Edward Handelsman, a pediatrician at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “It’s the first large, randomized clinical trial which absolutely, positively establishes this benefit to early treatment. And it provides a path — as far as I’m concerned a mandate — to start improving our methods of identifying [HIV-positive] infants early.” NIAID partly funded the study.

Preliminary results from this trial were made available to scientists in 2007. The early findings, now bolstered by final data, have led to a wholesale change in medical guidelines for treating infants who acquire HIV from their mothers in utero or during birth. The new treatment guidelines went into effect during the past year worldwide. They call for virus testing within three weeks after birth and immediate treatment for HIV-positive babies regardless of their immune CD4 T cell counts or symptoms.

Previously, HIV-positive babies were routinely treated only when their CD4 T cell count dropped sharply or when clear medical problems arose. But at that point the babies often plunged into a downward spiral.

“If you have a strong virus attack, the immature immune system not only loses CD4 T cells — other immune cells get depleted,” says study coauthor Avy Violari, a pediatrician at the University of the Witwatersrand in Johannesburg. This cascade weakens the body’s ability to fight other infections. HIV in an infant, she says, “is the worst-case scenario.”

Even so, the question of when to start treating a baby born HIV-positive had been mired in controversy, says Peter Havens, a pediatrician at the Medical College of Wisconsin in Milwaukee. Earlier guidelines had recommended that doctors wait until clear symptoms arose because of worries that early treatment might contribute to viral resistance to drugs or cause side effects in infants.

“But a lot of people have felt that, because HIV progresses so rapidly in young children, you might be better off treating everybody under a year of age,” Havens says. “This study clearly documents that.”

To clarify the value of early medication, Violari and her colleagues identified 377 infants in Cape Town and Soweto who were HIV-positive but whose CD4 T cell counts were still in the safe range. Starting in 2005, researchers began to assign infants of an average age of 7 weeks to one of two different regimens. One group of 125 infants got the standard treatment, in which medication was delayed until an infant’s T cells plunged or other symptoms arose. The other 252 infants were started on the cocktail of antiretroviral drugs promptly.

The children were then monitored at regular visits to clinics. But in June 2007, the scientists stopped assigning children to the delayed treatment group when evidence became clear that those treated earlier were benefiting. At that point, the children had been in the trial for 40 weeks, on average. During this time, 16 percent of the delayed-treatment infants died, compared with only 4 percent of those who had started receiving medication earlier. The most common infections striking both groups were gastrointestinal ailments, pneumonia, tuberculosis and meningitis. Babies getting treated earlier were more apt to experience a drop in neutrophils, a kind of white blood cell. But even with this side effect, their survival rates remained much higher.

As children grow, they become better able to live with an HIV infection. Thanks to improved drugs, the outlook for HIV-positive children has changed dramatically in the past two decades, Havens says. “The life expectancy for children with an HIV infection who can take their medicines … is unknown,” he says. “They’re not just growing into adulthood; [they are] running businesses and finishing college.”

But children born HIV-positive in Africa face a different reality, says Violari. “There are other disease, for example, and more challenges [such as] limited availability of drugs,” she says. The death rate during the first year of life for infants born with HIV in Africa is roughly 35 percent. By two years, it’s 52 percent, a 2004 study found.

She and her colleagues will continue to monitor the children in their study until 2011.