Kunjal Patel1,2, Jane Lindsey2, Konstantia Angelidou2, Grace Aldrovandi3, Paul Palumbo4. 1. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA. 2. Center for Biostatistics in AIDS Research (CBAR), Boston, Massachusetts. 3. Department of Pediatrics, University of California, Los Angeles, California. 4. Division of Infectious Diseases and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Abstract
OBJECTIVE: The aim of this study was to estimate the long-term metabolic effects of initiating a lopinavir/ritonavir (LPV/r)-based regimen as a first-line therapy for HIV-infected children less than 3 years of age in resource-limited settings. DESIGN: A prospective cohort study after conclusion of the P1060 randomized clinical trials (ClinicalTrials.gov Identifier: NCT00307151), with an overall follow-up of 7 years. METHODS:Longitudinal total cholesterol and triglyceride measures were compared between 222 and 227 children randomized to initiate LPV/r and nevirapine (NVP)-based regimens, respectively. Adipokines (adiponectin and leptin) and biomarkers of inflammation [C-reactive protein and interleukin (IL)-6], microbial translocation (lipopolysaccharide) and immune activation (sCD14), measured in 117 participants at a median of 45 weeks of follow-up, were also compared by a randomized arm. RESULTS:Mean total cholesterol and the percentage of participants with borderline or high total cholesterol was higher in the LPV/r arm from years 3 to 7 of follow-up than in the NVP arm (adjusted relative differences ranging from 10.9 to 23.4 mg/dl and adjusted relative risks ranging from a 60% increased risk to a more than four-fold increased risk for cholesterol≥170 mg/dl at 7 years of follow-up). Initiation of a LPV/r-based regimen was not associated with high triglycerides over follow-up or large differences in markers of metabolic syndrome, inflammation, microbial translocation or immune activation. CONCLUSION: Given the virologic superiority of LPV/r-based regimens in young children and open questions regarding the roll-out of dolutegravir in resource-limited settings, children are currently being maintained on LPV/r-based regimens. Our results suggest continual assessment of total cholesterol among young children initiating a LPV/r-based regimen to monitor cardiometabolic health.
RCT Entities:
OBJECTIVE: The aim of this study was to estimate the long-term metabolic effects of initiating a lopinavir/ritonavir (LPV/r)-based regimen as a first-line therapy for HIV-infectedchildren less than 3 years of age in resource-limited settings. DESIGN: A prospective cohort study after conclusion of the P1060 randomized clinical trials (ClinicalTrials.gov Identifier: NCT00307151), with an overall follow-up of 7 years. METHODS: Longitudinal total cholesterol and triglyceride measures were compared between 222 and 227 children randomized to initiate LPV/r and nevirapine (NVP)-based regimens, respectively. Adipokines (adiponectin and leptin) and biomarkers of inflammation [C-reactive protein and interleukin (IL)-6], microbial translocation (lipopolysaccharide) and immune activation (sCD14), measured in 117 participants at a median of 45 weeks of follow-up, were also compared by a randomized arm. RESULTS: Mean total cholesterol and the percentage of participants with borderline or high total cholesterol was higher in the LPV/r arm from years 3 to 7 of follow-up than in the NVP arm (adjusted relative differences ranging from 10.9 to 23.4 mg/dl and adjusted relative risks ranging from a 60% increased risk to a more than four-fold increased risk for cholesterol ≥170 mg/dl at 7 years of follow-up). Initiation of a LPV/r-based regimen was not associated with high triglycerides over follow-up or large differences in markers of metabolic syndrome, inflammation, microbial translocation or immune activation. CONCLUSION: Given the virologic superiority of LPV/r-based regimens in young children and open questions regarding the roll-out of dolutegravir in resource-limited settings, children are currently being maintained on LPV/r-based regimens. Our results suggest continual assessment of total cholesterol among young children initiating a LPV/r-based regimen to monitor cardiometabolic health.
Authors: Grace M Aldrovandi; Jane C Lindsey; Denise L Jacobson; Amanda Zadzilka; Elizabeth Sheeran; Jack Moye; Peggy Borum; William A Meyer; Dana S Hardin; Kathleen Mulligan Journal: AIDS Date: 2009-03-27 Impact factor: 4.177
Authors: Kunjal Patel; Jiajia Wang; Denise L Jacobson; Steven E Lipshultz; David C Landy; Mitchell E Geffner; Linda A Dimeglio; George R Seage; Paige L Williams; Russell B Van Dyke; George K Siberry; William T Shearer; Luciana Young; Gwendolyn B Scott; James D Wilkinson; Stacy D Fisher; Thomas J Starc; Tracie L Miller Journal: Circulation Date: 2013-12-23 Impact factor: 29.690