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Session 99 Poster Abstracts
Pathogenetic Mechanisms of Abnormalities of Glucose, Insulin, Lipid, and Mitochondrial Metabolism
Monday, 1:30 - 3:30 pm
Poster Hall


704    
Insulin Resistance and Apolipoprotein B Kinetics: A Comparison of Protease Inhibitor-, Efavirenz-, or Nevirapine-containing Antiretroviral Regimens
M Shahmanesh*1, S Das1, M Stolinski2, W Jefferson2, N Jackson2, G Gilleran1, R Cramb1, and M Umpleby2
1Univ. Hosp. Birmingham, Natl. Hlth. Svc. Trust, UK and 2Guy’s Kings Coll. and St Thomas’ Hospitals’ Schs. of Med., London, UK

Background:  Insulin resistance is seen in HIV patients taking protease inhibitor (PI) containing regimens but little information is available in non-PI-containing antiviral regimens. We studied insulin resistance in HIV-negative control and 3 HIV-positive patient groups and related this to apolipoprotein B (Apo-B) kinetics.

Methods:  We performed a cross sectional 9-hour tracer kinetic study with 13C-leucine to measure VLDL and IDL Apo-B absolute secretion rate and fractional catabolic rate. Insulin resistance was calculated by the homeostatic model (HOMA). Subjects were HIV negative (control, n = 12), treatment naïve HIV-positive patients (n = 15) or taking HAART containing PI (n = 14), efavirenz (EFV n = 14), or nevirapine (NEV n = 12). Groups had comparable body mass index but controls were significantly younger than PI-treated and treatment-naïve patients. EFV-treated patients were on anti-viral treatment for a significantly shorter time than the other treatment groups. All subjects underwent a whole body DEXA scan. Regional fat distribution was expressed as peripheral fat/body mass index or trunk fat/body mass index ratio. Comparison between groups was by Mann-Whitney test.

Results:  Differences in lipoprotein kinetics between groups is shown in the table. NEV-treated subjects has significantly lower glucose than those on PI or EFV (p <0.03) and also had lower HOMA compared to PI-treated (p <0.03) but not EFV-treated patients (p = 0.06). On a linear stepwise forward regression model trunk fat/body mass indes ratio (p <0.0001), VLDL cholesterol (p = 0.001), age (p = 0.005), and free fatty acids (p <0.05) correlated with HOMA, but not peripheral fat/body mass index ratio, VLDL absolute secretion rate, VLDL fractional catabolic rate, IDL absolute secretion rate and IDL fractional catabolic rate. There was no difference in peripheral fat or trunk fat among the antiviral treatment groups.

 

 

Age

Months on treatment (mean)

Glucose

mmol/L

HOMA

VLDL ApoB ASR

mg/kg/d

VLDL ApoB FCR

Pools/d

IDL ApoB ASR mg/kg/d

IDL ApoB FCR pools/d

Control (12)

31*

0

4.9

1.1

4.3

15.5***

3.3

10 ****

HIV Rx naive (15)

38.1

0

4.9

1.4

6

10.1

3.6

6.6

PI (14)

43.4

47.1

5.2

2.3

7.7

6.2

7.4

4.3

EFV (14)

36.9

24.1**

5.3

1.7

4.3

6.6

2.2

4.0

NEV (12)

39.7

40.8

4.7

0.9

3.9

7.2

1.6

3.1

* p <0.04 vs HIV treatment naïve and p = 0.006 vs PI, ** p <0.0001 vs PI and <0.005 vs NEV, *** p = 0.005 compared to all the other groups, **** p = 0.03 compared to the HIV treatment groups

Conclusions:  Nevirapine-containing regimens have a more favourable glucose-insulin profile than antiviral regimens containing efavirenz or protease inhibitors.

Keywords: Insulin resistance; lipoprotein; antiretroviral complications