Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy

Caroline J Chantry, Michael D. Hughes, Carmelita Alvero, Joseph S. Cervia, William A. Meyer, Janice Hodge, Peggy Borum, Jack Moye

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Abstract

OBJECTIVE. The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS. Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log 10 HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS. Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS. In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.

Original languageEnglish (US)
JournalPediatrics
Volume122
Issue number1
DOIs
StatePublished - Jul 2008

Fingerprint

HIV
Lipids
Glucose
Reverse Transcriptase Inhibitors
Protease Inhibitors
HIV-1
Somatomedins
RNA
Therapeutics
HDL Cholesterol
Intercellular Signaling Peptides and Proteins
Insulin
Dietary Cholesterol
Insulin-Like Growth Factor Binding Protein 1
Apolipoproteins
Nutrition Surveys
Dietary Fats
Centers for Disease Control and Prevention (U.S.)
Viral Load
Growth Hormone

Keywords

  • Apolipoprotein
  • Children
  • Cholesterol
  • Glucose
  • HIV
  • Immune reconstitution
  • Insulin
  • Insulin like growth factor binding protein
  • Insulin like growth factor-1
  • Insulin resistance
  • Triglycerides
  • Viral load

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy. / Chantry, Caroline J; Hughes, Michael D.; Alvero, Carmelita; Cervia, Joseph S.; Meyer, William A.; Hodge, Janice; Borum, Peggy; Moye, Jack.

In: Pediatrics, Vol. 122, No. 1, 07.2008.

Research output: Contribution to journalArticle

Chantry, CJ, Hughes, MD, Alvero, C, Cervia, JS, Meyer, WA, Hodge, J, Borum, P & Moye, J 2008, 'Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy', Pediatrics, vol. 122, no. 1. https://doi.org/10.1542/peds.2007-2467
Chantry, Caroline J ; Hughes, Michael D. ; Alvero, Carmelita ; Cervia, Joseph S. ; Meyer, William A. ; Hodge, Janice ; Borum, Peggy ; Moye, Jack. / Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy. In: Pediatrics. 2008 ; Vol. 122, No. 1.
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abstract = "OBJECTIVE. The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS. Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4{\%} were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4{\%} and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4{\%}, log 10 HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS. Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4{\%} increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS. In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4{\%} increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.",
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AU - Meyer, William A.

AU - Hodge, Janice

AU - Borum, Peggy

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N2 - OBJECTIVE. The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS. Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log 10 HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS. Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS. In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.

AB - OBJECTIVE. The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS. Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log 10 HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS. Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS. In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.

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KW - Immune reconstitution

KW - Insulin

KW - Insulin like growth factor binding protein

KW - Insulin like growth factor-1

KW - Insulin resistance

KW - Triglycerides

KW - Viral load

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