Asymptomatic HIV-infected Newborns May Benefit From Early Drug Treatment, Stanford Study Shows

"This is an important finding because there's been a lot of controversy in the literature as to whether infected but asymptomatic infants should be started on therapy right away," said the study's senior author Yvonne Maldonado, MD, a pediatric infectious disease expert at Lucile Packard Children's Hospital and an associate professor of pediatrics at Stanford's School of Medicine.

Without any kind of treatment, about 20 to 30 percent of HIV-infected infants will develop AIDS by around 4 months of age. The rest will not have advanced symptoms until they are about 6 years old. The study, published May 11 in the Journal of the American Medical Association, suggests that early treatment might be appropriate for at least some apparently healthy infected infants.

"There is a significant difference in the likelihood of disease progression [with earlier treatment], even though there is only about a month separating the initiation of therapy in the two groups," Maldonado said. "And none of the children who received triple therapy progressed to AIDS before their third birthday, regardless of the age at which they began therapy." (Therapy with a combination of three drugs, known as highly active antiretroviral therapy, or HAART, was not available when the study began in 1988.)

Current guidelines for treating HIV-infected infants leave the decision of when to begin treatment to the child's physician-in part because the long-term effects of ongoing antiretroviral treatment are not known. Concerns about the drugs' possible toxic side-effects and the development of viral resistance to available treatments must be balanced against a desire to do everything possible to keep infected children healthy.

Maldonado and her colleagues collected data from hospitals throughout northern California over a 17- year period. Statistical calculations indicate that their sample of 205 children represents nearly every HIV-infected child born in the area during that time-an unbiased sample that allowed them to analyze all infected babies, not just the sickest. "We were able to analyze children with the full spectrum of disease across many years, rather than using mathematical models to predict the development of illness in the children," said Maldonado. "We were able to see the real distribution of illness, what kinds of treatment the children were given and the ages when they started treatment."

The researchers divided the HIV-infected newborns into three groups: those born from 1988 to 1991, from 1992 to 1995 and from 1996 to 2001 based on the types of therapy available in those years. Members of the early group were usually evaluated for infection by their first birthday; those in the middle and late groups were assessed within the first month. Those in the late group benefited from the introduction of a special type of antiretroviral drug called a protease inhibitor. They followed the children for the first three years of life, tracking at what age they developed AIDS and the rate of survival through their third birthday.

As might be expected, infants born later in the study period were more likely to receive triple therapy and less likely to experience AIDS-related complications or death. In fact, none of the 23 children who received triple therapy died or developed AIDS before their third birthday. In contrast, about 55 percent of the children in the first two groups died of AIDS. When the researchers compared the outcomes in the first two groups, they found that any type of antiretroviral therapy delayed disease progression and enhanced survival.

"We've clearly shown that early treatment of asymptomatic infants-no matter what it is-makes a big difference in preventing or delaying the progression of the disease," said Maldonado. "Now we have to move forward to figure out if this treatment is going to be appropriate for everyone."

Clinical trials are needed to determine if every infected newborn should be treated or if some subsets of infants will benefit more than others, Maldonado explained. In the meantime, the findings emphasize the importance of testing pregnant women for HIV and watching for signs of infection in the newborns of women who have tested positive for HIV.

The study was supported by funding from the Office of AIDS at the California Department of Health Services. Researchers from 10 institutions participated in the study, including Maldonado and three others from Stanford's Department of Pediatrics.