In the first prospective study in the United States to look at the effect of combination therapy that includes protease inhibitors on HIV-1 infected children and adolescents, researchers from the Pediatric AIDS Clinical Trials Group (PACTG) and the Harvard School of Public Health (SPH) found that mortality rates among the study participants were dramatically reduced. The study appears in the latest issue of the New England Journal of Medicine.
Combination therapy including protease inhibitors has been available since 1996 for adults and has slowed the progression of HIV-1 and drastically reduced the rate of mortality. In 1993, PACTG researchers undertook the development of the “Pediatric Late Outcomes Protocol, PACTG 219,” to prospectively collect data on HIV-infected and uninfected children who had been exposed to antiretroviral drugs. According to 1996 study data, only 7 percent of the children were receiving combination therapy including protease inhibitors. That rate steadily grew and by 1999, 73 percent were receiving the therapy. Within that time mortality declined among the group from 5.3 percent in 1996, to 2.1 percent in 1997, 0.9 percent in 1998, and 0.7 percent in 1999. The study participants were composed of 1,028 HIV-1 positive children and adolescents who were enrolled in PACTG research sites throughout the United States prior to 1996 and were followed through 1999.
The researchers took into account specific variables among the study’s participants, such as ethnicity, height, weight, sex, age, and parent’s education level, and found that the results of the combination therapy including protease inhibitors remained uniformly successful. Other studies indicate that combination therapy not only decreases the risk of death but improves growth and immune function, and lowers the incidence of infectious complications.
Among adults, combination therapy including protease inhibitors has been associated with side effects such as hyperglycemia, lipodystrophy (odd distribution of fat), bone mineral loss, and other complications, issues that the authors suggest need to be addressed so that children who undergo the combination therapy in their formative years are not adversely affected.
“The study documents very substantial reductions in mortality among children and adolescents. Prior to this we had evidence of improvements in viral loads, and a sense of reduced death – but now we have clear evidence,” said Steven Gortmaker, senior lecturer in the department of health and social behavior at the School of Public Health and lead author of the study. “Perhaps most importantly, we see large and equivalent reductions in mortality among all parts of the study population – boys and girls, from households with different socioeconomic background, among different ethnic groups, and across the children’s age groups. Given concerns about households and children being able to adhere to these regimens, this is reassuring news. We do still need to be aware of complications, side effects, and equal access to the medical centers that provide combination therapy with protease inhibitors.”
The research was supported by grants from the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases and the Pediatric-Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development.