Impact of Protease Inhibitor-Containing Combination Antiretroviral Therapies on Height and Weight Growth in HIV-Infected Children

Abstract

ABSTRACT. Objective. To examine beneficial or detrimental effects of protease inhibitor (PI)-containing antiretroviral regimens on height and weight growth in children with human immunodeficiency virus (HIV) infection.Methods. A prospective cohort study was conducted of 906 HIV-infected children, from pediatric research clinics in the United States, who were between 3 months and 18 years of age and who had height and weight assessed in 1995 (before introduction of PIs in this population) and at least once more through 1999. Changes in age-and gender-adjusted height and weight growth associated with PI use were assessed.Results. Compared with a healthy reference population, children were more affected in height (mean z score: ؊0.90 [18th percentile]) than in weight (mean z score: ؊0.42 [34th percentile]) at baseline (1995). Two thirds of children received at least 1 PI during 1996 to 1999. In the multivariate mixed effects regression models adjusted for baseline log 10 CD4 cell count, baseline age, gender, and race/ethnicity, the use of PIs was associated with per-year gains of 0.13 z scores in height and 0.05 z scores in weight relative to the expected growth with non-PIcontaining regimens (eg, after 1 year of PI use, a representative 6-year-old boy in our study would be approximately 0.7 cm taller and 0.1 kg heavier than if he had not received PIs). No significant differential effects of PIs on height or weight growth according to specific agents or children's sociodemographic or clinical characteristics were found.Conclusions. Although the use of PI-containing regimens was not associated with growth retardation, it was associated with only small annual increments in height and weight growth in HIV-infected children. Pediatrics 2001;108(4). URL: http://www.pediatrics.org/cgi/content/ full/108/4/e72; HIV-1, protease inhibitor, growth, children.ABBREVIATIONS. PI, protease inhibitor; HIV, human immunodeficiency virus; PACTG, Pediatric AIDS Clinical Trials Group; HAZ, height-for-age-and-gender z score; WAZ, weight-for-ageand-gender z score. P rotease inhibitors (PIs) have been used increasingly in the treatment of human immunodeficiency virus (HIV)-infected children since the mid-1990s. However, little is known about the longterm effects of PI-containing combination antiretroviral therapies on height and weight growth in pediatric populations. HIV-infected children fall behind HIV-uninfected children who are born to HIVinfected mothers in age-and gender-appropriate height and weight in the first few years of life. [1][2][3] Studies that examined the effect of zidovudine on height and weight gain in HIV-infected children were limited by sample size and produced mixed results. 2,4 Some small clinical studies [5][6][7][8] suggested that PI treatments may have beneficial effects on weight and/or height growth in HIV-infected children, but other studies found no improvements in growth associated with the use of PI-containing regimens. 9 -11 The hope is that PI treatments may reverse some of the negative effects of HIV ...

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

“…For example, for a 6-year-old boy with a WAZ score of −0.78 (median at the time of database freeze), the 0.25 difference in z scores at year 5 predicted by adjusted ITT analyses translates to a weight difference of approximately 0.7 kg. Reasons for these findings may include the poor palatability ( particularly with liquid formulations), appetite suppression, and metabolic effects associated with LPV/r and other protease inhibitors [23][24][25]. Interestingly, despite the reputation of liquid LPV/r formulations for challenging administration, the IM-PAACT P1060 trial demonstrated remarkable acceptability and adherence among these young infants, with desirable short-and long-term outcomes.…”

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

“…PACTG 219 was designed to assess late outcomes of in utero and neonatal exposure to antiretroviral drugs in clinical trials, as well as the long-term effects of antiretroviral treatment among children with HIV-1 infection, as described previously. 11,13,18 Human-subject research review boards at participating sites in the United States and Puerto Rico approved the research protocol. Before enrollment, written informed consent was obtained from participants' parents or legal guardians or from participants who were above the legal age limit.…”

“…Studies showed that PI therapy was initiated sooner among children with lower CD4 ϩ cell counts and lower height and weight z scores, which introduces the need to control for confounding by severity of illness with indication for treatment. 11,13,17 Mean differences in QOL scores between treatment groups were initially estimated with univariate linear regressions. Multivariate regressions were then used to estimate differences between treatment groups while controlling for clinical factors associated with receipt of PI therapy and sociodemographic characteristics.…”

“…10 The use of PI therapy has been found to reduce morbidity and mortality rates among HIV-infected children and adolescents 11,12 and has been shown to increase height and weight growth. 13,14 To date, however, studies have not examined the association of PI therapy with children's health-related quality of life (QOL).…”

The Use of Second-Generation Antipsychotics and the Changes in Physical Growth in Children and Adolescents with Perinatally Acquired HIV

“…20 The main effect of PI use was significant in all final models (except for the long-term model for risperidone, which may be a function of small sample size) and is consistent with the findings in other studies. 35,36 However, the presence of a significant interaction between PI use and prescribed SGA= risperidone that was found in investigative modeling of both the short-term and long-term models provides some evidence that the effect of simultaneous SGA and PI exposure on change in BMI z score may be stronger than the sum of the individual effects of these two classes of drugs. This enhanced effect of the two medication classes, with known metabolic abnormalities in pediatric populations, might be due to CYP 450 interaction between the PIs and SGAs, particularly risperidone, which is metabolized primarily through the CYP 450 2D6, an enzyme blocked by the PIs indinavir and ritonavir.…”