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

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.

FIGURE 1

Mean metabolic z scores at study weeks 0, 24, and 48 in the P1010 study population.