Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy.
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.
Department of Pediatrics, University of California Davis Medical Center, Sacramento, California 95817, USA. caroline.chantry@ucdmc.ucdavis.edu
Caroline J
CJ
Chantry
Michael D
MD
Hughes
Carmelita
C
Alvero
Joseph S
JS
Cervia
William A
WA
Meyer
Janice
J
Hodge
Peggy
P
Borum
Jack
J
Moye
D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006706:Homeostasis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D009749:Nutrition Surveys; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008078:Cholesterol, LDL; D018970:Insulin-Like Growth Factor Binding Protein 1; D008055:Lipids; D008075:Lipoproteins, HDL; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I