The Effect of Protease Inhibitor Therapy on Growth and Body Composition in Human Immunodeficiency Virus Type 1-Infected Children

Abstract

ABSTRACT. Objective. To determine the effect of protease inhibitors (PIs) on growth and body composition in children with human immunodeficiency virus type 1 (HIV-1) infection.Background. HIV-1-infected children have chronic problems with both linear growth and weight gain. Viral load may directly influence growth and nutritional status of HIV-1-infected children with reduction of viral load improving the nutritional condition.Design/Methods. Data from 67 patients who initiated PI therapy between 1996 and 1999 and who were enrolled in a prospective, longitudinal study of growth and nutrition in HIV-1-infected children were analyzed. Outcomes included pre-PI versus post-PI measures of height, weight, weight-for-height, triceps skinfold thickness, and arm muscle circumference. Predictor covariates included age, race, gender, Tanner stage, CD4 z score, Centers for Disease Control and Prevention stage, route of infection, plasma HIV-1 RNA, other antiretroviral therapy, recommended daily allowances for calories, treatment with megestrol acetate, and PI therapy.Results. Sixty-seven children were followed for a median of 2.4 years with a total of 362 visits (median: 5 visits; range: 1-12). During follow-up, they received PIs for a median of 5 months. Fifty-one percent were girls, 54% black, 15% Hispanic, and 25% white. The mean age at first visit was 6.8 years. In a univariate analysis, weight z score (؊0.67 to ؊0.35) and weight/height z score (0.25-0.76) improved on PI therapy. Using repeated-measures regression analysis, controlling for the above named covariates, PI treatment showed a significant effect on weight z score (increase in z score by 0.46), weight/height z score (increase in z score by 0.49), and arm muscle circumference (increase in percentile by 11.5). A borderline effect was found for height z score (increase in z score by 0.17) and no effect was found for triceps skinfold thickness. In a separate analysis, PI therapy increased CD4 counts twofold and reduced plasma HIV-1 RNA copies by 79%.Conclusion. In addition to a significant reduction in viral load, PI therapy in children has a positive effect on several growth parameters, including weight, weight/ height, and muscle mass. 1 Survival time and quality of life for children living in countries with access to highly active antiretroviral therapy (HAART) have improved because of advances in medical therapy. Indeed, the goal of therapy in the United States has shifted from delayed disease progression to indefinite viral suppression. 2-4 With these developments, new questions relating to longterm changes in growth and body composition in both adults and children have arisen.Understanding the link between nutrition and the new therapeutic options available is critical, because nutritional status has been shown to be associated with pediatric HIV-1 disease progression. 5,6 Growth patterns before HAART therapy of HIV-1-infected children in developed countries are fairly well established, 7-11 although the exact mechanisms of these growth abnormalities are n...

Treatment With Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Children Is Associated With a Sustained Effect on Growth

“…However, in a recent study in HIV-1-infected children, protease inhibitors were found to cause a significant increase in weight-for-height and a dramatic improvement in lean body mass over a short interval and had no immediate influence on fat mass, although there was a trend toward increased fat mass, with longer follow-up time. 28 This suggests that in the children whose BMI increased in our study, namely the children with an advance stage of clinical infection and responders to HAART with a high increase in CD4 ϩ T-cell count, lean body mass also increased. The difference of the effect of HAART on body composition between children and adults could be attributed to the fact that children are still growing so their metabolism is different, but additional research is needed.…”

“…28,30,31 However, the follow-up time of these studies was only 24 weeks. A positive influence on growth has been observed as a result of NRTI mono therapy or dual therapy during this same period.…”

Maternal and Infant Factors Associated With Failure to Thrive in Children With Vertically Transmitted Human Immunodeficiency Virus-1 Infection: The Prospective, P2C2 Human Immunodeficiency Virus Multicenter Study

“…Yet there is evidence that protease inhibitor therapy positively influences nutritional status, including improving body composition. 43 There may have been other factors, such as neurologic deficits, that can influence growth yet were not recorded in the study because it was not designed with growth changes as a primary outcome. However, this study included a large, systematically studied group of HIV-1-infected infants, tracked from birth with close follow-up of important clinical variables.…”

Síndrome da lipodistrofia e fatores de risco cardiovasculares em crianças e adolescentes infectados pelo HIV/AIDS em uso de terapia antirretroviral de alta potência

“…Such finding is in agreement with a prospective study conducted with children according to which, after the regression model analysis, the therapy with PI improved weight, weight/height, and upper-arm circumference, with significant increased weight since the first assessments. 14 However, a retrospective study found an increase in weight and height after the use of HAART without changes in the BMI. 15 The low height found in the adolescents included in the present study may have been caused by the longer exposure to HIV before the HAART started to be used.…”