9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV


19-21 July 2007, Sydney, Australia

DYSLIPIDAEMIA IN VERTICALLY INFECTED CHILDREN AND YOUTH ON PROTEASE INHIBITOR (PI)-CONTAINING ANTIRETROVIRAL THERAPY (ART): PRELIMINARY RESULTS OF PACTG 1045

Antiviral Therapy 2007; 12(Suppl. 2):L6 (abstract no. O-04)

GM Aldrovandi1, JC Lindsey2, D Jacobson2, B Heckman3, A Zadzilka3, E Sheeran4, J Moye5, P Borum6, WA Meyer III7, D Hardin8, E DeCarlo9 and K Mulligan10
1Children’s Hospital of Los Angeles, Los Angeles, CA, USA; 2Harvard School of Public Health, Boston, MA, USA; 3Frontier Science and Technology Research Foundation, Amherst, NY, USA; 4Social and Scientific Systems, Inc., Silver Spring, MD, USA; 5National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA; 6University of Florida, Gainesville, FL, USA; 7Quest Diagnostics, Inc., Baltimore, MD, USA; 8The Ohio State University, Columbus, OH, USA; 9National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA; 10University of California San Francisco, San Francisco, CA, USA

AIM: To determine the prevalence of lipid and glucose abnormalities and their association with ART among vertically infected youth.

METHODS: HIV+ subjects, 7–24 (median 12) years, stratified by sex, race/ethnicity and Tanner stage, were randomly selected at 37 sites and enrolled in groups on PI≥12 months (PI; n=161 [90M/71F]) or non-PI containing ART (NoPI; n=79 [37M/42F]). Matching seronegative controls (HIVneg; n=146 [84M/62F]) were recruited in the same clinics. Measurements included fasting lipids, insulin and glucose, a 2-h oral glucose tolerance test, fat distribution by DXA and ART and medical histories. Medians were compared with HIVneg by Wilcoxon rank sum tests.

RESULTS: The PI group tended to have longer total exposure to ART (10.0 versus 9.0 years; P=0.055 versus NoPI). There were no differences in current CD4 and HIV RNA, but subjects on PI had lower nadir CD4 and higher peak HIV RNA (P<0.001 versus NoPI). Lopinavir/r and nelfinavir were the most commonly used PIs at the time of study. Both HIV+ groups had lower z-scores for height and weight, as well as total, trunk and limb fat, compared with HIVneg. Triglycerides (TG) were significantly higher in both HIV+ groups. The PI group, but not NoPI, had higher total, LDL and non-HDL cholesterol and lower HDL cholesterol than HIVneg. A greater proportion of subjects on PI had abnormal values for each lipid parameter. Fasting insulin and HOMA-IR were higher in both HIV+ groups (insulin 10.0, 10.5 and 7.0 mIU/ml in PI, NoPI, and HIVneg, P<0.025 for both groups versus HIVneg; HOMA-IR 2.0, 2.3 and 1.5, respectively, P=0.049 and 0.019 versus HIVneg). Fewer than 5% of subjects in any group had abnormal 2 h glucose.

Table 1. (Abstract O-04)
  P-value versus
HIVneg
  PI No PI HIVneg PI No PI
TG, mg/dl 134 82 67 <0.001 0.004
  % ≥150 45 11 8  
Total chol, mg/dl 174 153 153 <0.001 0.479
  % ≥200 29 7 10  
LDL-C, mg/dl 99 89 89 0.002 0.323
  % ≥130 19 3 6  
HDL-C, mg/dl 44 46 49 <0.001 0.112
  % <40 M/50F 46 38 32  
Non HDL-C, mg/dl 130 109 105 <0.001 0.952
  % ≥160 24 3 3  

CONCLUSION: In this large study of randomly selected youth, there was a high prevalence of lipid abnormalities among those on PI. Insulin and HOMA-IR were higher in both PI and NoPI, but the prevalence of glucose intolerance was relatively low. Dyslipidaemia and insulin resistance may accelerate lifetime risk of cardiovascular disease in vertically infected youth with extensive exposure to ART.

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2007-07-24
O-04

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