Paper # 867 
Effect of Lopinavir/Ritonavir on Lipids in HIV-infected Children
Natella Rakhmanina*1,2, J van den Anker1,2, M K Scott3, S Soldin4, K Williams1, and M Neely5
1Children’s Natl Med Ctr, Washington, DC, US; 2George Washington Univ, Washington, DC, US; 3Loyola Univ Chicago, IL, US; 4Georgetown Univ, Washington, DC, US; and 5Univ of Southern California, Los Angeles, US
Background: Lopinavir/Ritonavir (LPV/RTV) is widely
used in HIV-infected children. In adults LPV and RTV exposure has been
associated with elevated total cholesterol (TCH) and triglycerides (TG). The
aim of this study was to determine how LPV/RTV exposure affects the lipid
profiles of pediatric treatment-experienced patients.
Methods: Data were prospectively (52 weeks)
collected from HIV-infected children (4 to 17 years) receiving single PI-based
therapy with LPV/RTV. The area under the concentration-time curves (AUCs) were
estimated for LPV and RTV using non-parametric population models fitted to 7
concentrations measured by a published mass-spectrometry assay over a single 12
hr interval with an observed dose intake within 2 months after enrollment. TCH
(including LDL and HDL) and TG were measured during the pharmacokinetic study
after overnight fasting prior to administration of LPV/RTV. Lipids were
classified according to the National Cholesterol Education Program (NCEP)
guidelines. Multivariate linear regression models were used to estimate primary
associations between plasma lipids or ordered NCEP category and LPV/RTV AUCs,
with inclusion of LPV/RTV treatment duration, body mass index (BMI), age, sex,
or HIV RNA viral load (VL) <400 copies/mL during the study period as
covariates if they changed the primary association by >20%.
Results: In this study, 52 children were enrolled
(median age 11.6 years (5.3 to 17.7); male/female = 1:1). The majority of
patients had a healthy weight (75%) with 9.6% overweight and 7.7% obese
children. The median BMI was 17.5 (14 to 23.5). Median duration of LPV/RTV
treatment was 2.6 years (0.2 to 6.6 years); 27 (52%) had a VL<400 at least
once during the study. Number of patients in each NCEP category is below.
|
NCEP Category
|
Total CH
|
HDL
|
LDL
|
TG
|
|
Normal
|
26
|
11
|
29
|
20
|
|
(50.0%)
|
21.2%
|
(56.9%)
|
(39.2%)
|
|
Borderline
|
16
|
27
|
14
|
8
|
|
(30.8%)
|
(51.9%)
|
(27.5%)
|
(15.7%)
|
|
Abnormal
|
10
|
14
|
8
|
23
|
|
(19.2%)
|
(26.9%)
|
(15.7%)
|
(45.1%)
|
No association was found between NCEP category and LPV or
RTV AUC, nor was any association found between lipids and LPV AUC. In contrast
for every increase in RTV AUC of 10 mg*h/L, when adjusted for age and duration
of LPV/RTV therapy, there was a mean TCH rise of 21 mg/dL (P =0.04)
and HDL rise of 8 mg/dL (P =0.006).
Conclusions: RTV, but not LPV, AUC was significantly
associated with elevated TCH in HIV-infected children, largely driven by
RTV-associated increases in HDL. Further studies on RTV associated lipid
abnormalities in children are warranted.
|
