Abstract and Introduction
Abstract
Objectives: To describe 5-year growth, survival, and long-term safety among children exposed to nevirapine or zidovudine in an African perinatal prevention trial, HIVNET 012.
Methods: All study children who were alive at the age 18 months were eligible for an extended follow-up study. Children whose families consented were enrolled and evaluated every 6 months from 24 to 60 months. At each visit, history, physical examination, and growth measures were taken. From these measurements, Z scores based on World Health Organization (WHO) standards were computed. Serious adverse event data were collected. Data from the initial and extended follow-up cohorts were included in the analysis.
Results: Five hundred twenty-eight study children were alive at the age 18 months, and 491 (426 HIV uninfected and 65 infected) were enrolled into the follow-up study. Both exposed but uninfected children and HIV-infected children were substantially below WHO growth standards for weight and height. Head circumference Z scores for uninfected children were comparable with WHO norms. Five-year survival rates were 93% for uninfected children versus 43% for infected children. Long-term safety and growth outcomes in the 2 study arms were similar.
Conclusions: Both infected and uninfected children in the 5-year HIVNET 012 follow-up showed poor height and weight growth outcomes, underscoring the need for early nutritional interventions to improve long-term growth of all infants born to HIV-infected women in resource-limited settings. Similarly, the low 5-year survival among HIV-infected children support the importance of early initiation of antiretroviral therapy. Both peripartum nevirapine and zidovudine were safe.
Introduction
HIV/AIDS continues to have a profound effect on the health of children worldwide. Despite advances in prevention of mother-to-child HIV transmission (MTCT), an estimated 330,000 children become infected through MTCT in resource-limited settings (RLSs) each year.
In the United States and Europe, the effects of HIV on pediatric growth, morbidity, and mortality have been studied extensively among both HIV-infected and exposed uninfected children through prospective perinatal cohort studies. These studies have longitudinally tracked the growth and development, complications of HIV and treatment, hospitalizations, quality of life, and survival of children born to HIV-infected women, before and after the availability of potent combinations of pediatric antiretroviral treatment (ART).
However, in RLSs, with the largest pediatric HIV burden, there is a paucity of literature addressing the long-term growth and survival of infants born to HIV-infected women, including whether there are any late sequelae of exposure to perinatal antiretroviral (ARV) interventions. The limited numbers of published research studies have focused primarily on comparisons of infant morbidity and mortality in children aged younger than 36 months born to HIV-infected mothers.
The HIVNET 012 clinical trial, which followed up HIV-exposed infants from birth to the age 18 months, and its companion rollover protocol, which followed up participant children from 24 months up to age 5 years, provided a unique opportunity to address longer-term growth, morbidity, and survival and to assess potential late sequelae from short peripartum ARV exposure. The overall aim of this analysis was to compare the long-term growth and survival among the HIV-infected and -uninfected children in the HIVNET 012 cohorts during a time period when ART was not widely available. In addition, we examined the most common causes of hospitalizations in HIV-uninfected and -infected infants. Finally, we monitored for any late sequelae over the first 5 years of life among children born to mothers in the short course zidovudine (ZDV) compared with the nevirapine (NVP) study arms of HIVNET 012.