Triglycerides,LDL cholesterol and HOMA score predict the virological response in HIV/HCV co-infected patients treated with Pegylated interferon alpha 2a and Ribavirn

P.Nasta MD; F. Gatti MD, G. Cologni MD, A. Matti MD, M. Mendeni MD, L. Biasi MD, M. Puoti Prof and G. Carosi Prof.

Paola Nasta MDInstitute of Infectious and Tropical Diseases

University of BresciaP.Le Spedali Civili, 1 25123 Brescia, ITALY

Tel +39-030-3995665E-mail: paola.nasta@tin.it

Institute of Infectious and Tropical Diseases, University of Brescia, Italy

CONCLUSIONS

Background

Variable A All RVR yes p AOR(95% CI) p EVR yes p OR(95% CI) p SVR yes p AOR(95% CI) p

Pts Number 96 41/96(43) 59/96(61,5) 28/77(26,4)

Age yrs M (+SD);

Median (IQR)

42,5 (5,1)

42,5 (28-45,5)

42,2(6) 0,6 41,8(6,1) 0,1 40,8(+5,1) 0,02

Female n (%) 16 (16,7) 10(25) 0,1 13(22,8) 0,1 6(23,1) 0,2

Body weight kg M (+SD);

Median (IQR)

70,1 (12,8)

68 (61-67,5)

66(11,5) 0,02 68(11,1) 0,04 69,2(13,4) 0,7

BMI Kg /m2 M (+SD);

Median (IQR)

23,6 (2,2)

23,3(21,2-25,5)

22,9(3,1) 0,05 23,2(3) 0,05 23,2(3) 0,3

IDU n (%) 85 (88,5) 36(90) 0,4 51(89,5) 0,3 24(92,3) 0,2

Smokers n (%) 48 (51,1) 24(61,5) 0,05 32(57,1) 0,1 17(65,4) 0,02

On methadone n (%) 6 (6,3) 4(10) 0,2 4(7) 0,6 1(3,8) 0,3

Alcohol users n (%) 28 (30,1,) 13(34) 0,2 18(32,7) 0,2 6(23,1) 0,3

Duration of HCV infection yrs M (+SD)

Median (IQR)

10,1 (5,2)

9 (1-21)

13,9(5,9) 0,1 10,6(5,6) 0,1 16,6(5,8) 0,5

Duration of HIV infection yrs M (+SD)

Median (IQR)

15,8 (9,5)

16 (10-20)

13,9(6,0) 0,06 14,2(6) 0,06 13,6(5,8) 0,02

CD4 nadir cell/mmc M (+SD)

Median (IQR)

197 (141)

190 (96-269)

211(151) 0,2 214(154) 0,1 217(167) 0,3

CD4 zenith M (+SD)

Median (IQR)

688 (245)

680 (507-851)

671(239) 0,6 669(228) 0,4 706(221) 0,9

CDC class C n (%) 22(22,5) 13(21) 0,4 6(23,1) 0,3 6(23,1) 0,3

ART exposure yrs M (+SD);

Median (IQR)

9,4(5,1)

10 (5-14)

8,1(5,1) 0,01 8,4(5,1) 0,009 7,9(5) 0,01

Currently On HAART n (%)

PI based n (%)

ABC based n (%)

85 (88)

73 (76)

49(16,7)

33(80,5)

39(66,1)

7(17,5)

0,03

0,08

0,5

49(83,1)

37(60,7)

9(15,3)

0,02

0,06

0,4

25(89,3)

37(61)

6(21,4)

0,5

0,06

0,3

HIV-RNA undetectable n (%) 85 (88%) 33(80,5) 0,03 49(83,1) 0,02 25(89,3) 0,5

Bl CD4 cell/mmc M (+SD)Median (IQR) CD4 > 500 cell /mmc n (%)

488 (200)

446 (327-593)

39(40,6)

457(181)

13(31,7)

0,2

0,1

468(184)

22(37,3)

0,3

0,3

492(214)

8(28,6)

0,8

0,08

Genotype 1 -4 n (%) 51(53) 12(29,3) <0,001 0,05(0,007-0,3) 0,001 19(32,2) <0,001 0,04(0,009-0,2) <0,001 10 (35,7) 0,002 0,1(0,05-0,6) 0,006

Advanced liver disease n (%) 53(57,6) 20(50) 0,1 26(48,1) 0,02 9(34,6) 0,008

Cirrhosis n (%) 28(29,2) 7(17,1) 0,01 13(22,8) 0,06 5(17,9) 0,06

HCVRNA log IU/mL M(+SD)

Median (IQR)

HCVRNA <400.000 IU/mL n (%)

6,05(6.3)

5,7(4,9-7,0)

39(40,6)

5,71(5,79)

21(51,2)

0,003

0,07

5,8(+5,9)

28(47,5)

0,02

0,1

5,7(5,8)

17(60)

0,003

0,01 4,9(1,4-17,3) 0,01

Tot Col mg/dL M (+SD);

Median (IQR)

Tot Chol > 200 mg/dl n(%)

Chol LDL mg/dl M (+SD);

Median (IQR)

Chol HDL mg/dl M (+SD);

Median (IQR)

Chol HDL <40 n(%)

161 (41,5)

159 (133-180)

14(14,6)

98(30,5)

93(74-117)

44,5 (13,5)

42 (32-52)

31(34,8)

164(40,7)

6(14,6)

106(27)

47,3(15,1)

10(26,3)

0,4

0,6

0,02

0,04

0,08

1,0(1-1,06) 0,02

160(+41)

8(14)

99(29,4)

46,5(15)

37(69,8)

0,7

0,5

0,7

0,05

0,08

162(37)

3(10,7)

102(29)

43(11)

6(25)

0,6

0,5

0,2

0,8

0,2

TGD mg/dL M (+SD);

Median (IQR)

TGD > 150 mg/dL n(%)

145 (87,6)

125 (82-181)

34(35,4)

112(52)

6(14,6)

0,0004

<0,001 0,16(0,03-0,8) 0,003

0,001

0,002 0,2(0,06-0,8) 0,02

142(111)

8(28,6)

0,07

0,1

HOMA-IR < 3 n (%) 35 (46,1) 25(62,5) <0,001 7,3(1,4-38,5) 0,01 31(67,4) 0,003 5,4(1,4-20,4) 0,01 20(71,4) 0,005 6,5(1,7-24,1) 0,004

Results Variables correlated with Rapid (RVR), Early (EVR) and Sustained (SVR) virologic response

Aim and Methods

HIV-HCV co-infected patients who started pegylated interferon alfa-2a

(180 mcg/week) and Ribavirin1000-1200 mg/die(14 mg/kg(day) from January 2005

have been enrolled.

At fasting insulin, glucose, total cholesterol, LDL (Low Density Lipoprotein),

HDL (High Density Lipoprotein) and triglycerides (TGD) plasma level were measured

in all patients on the first day of treatment with PegIFN/RBV and every three months

HOMA-IR (HOMA: HOmeostasis Model of Assessment ) has been

calculated as fasting insulin (mIU/L) × fasting glucose (mmol/L) ÷ 22.5;

(normal range 0,7-2,25).

HCV-RNA was measured by quantitative PCR assay (Versant 3.0) at baseline and HCV-RNA by qualitative PCR assay (COBAS 2.0) after 4 weeks of treatment

and every three months.

Patients with at least 3 months of anti HCV treatment entered in the analysis.

Association between lipid and glucose parameters and RVR (Rapid Virologic Response),

EVR (Early Virological Response) and SVR (Sustained Virological Response )

has been assessed

Descriptive statistics are calculated for all the variables, data are expressed as number and percentage or mean (+SD) and median (IQR). All statistical analyses will be conducted at the alpha = 0.05 level and will be two-tailed.

Baseline Variables in patients with or without RVR,EVR and SVR were compared using the Chi square test and Fisher’s exact test Variables possibly associated with RVR;EVR, SVR achievement were evaluated using the logistic regression model. Analyses were performed using Epi InfoTM version 3.3.2 (February 9,2005)

HCV positive persons had an increase risk for type 2 diabetes mellitus particularly

if cirrhotic (Knobler H et al. Mayo Clin Proc; 2000) and when older than 40 years (Mehta SH et al. Ann Intern Med; 2000)

In HIV-HCV co-infected patients, insulin resistance is caused by both HCV infection and HAART therapy particularly when based on protease inhibitors (Braitstein P et al. AIDS; 2004) and thymidine analogues (Martin A et al. J Antimicrob and Chemoter; 2005)

In HIV/HCV co-infected subjects, insulin resistance and LDL cholesterol

are emerging as important host factors in the prediction of response in non diabetic patients treated with PEG-IFN plus ribavirin (Nasta P. et al, AIDS 2008; del Valle J et al. AIDS 2008)

Metabolic parameters as insulin resistance (HOMA >3), Low Density Lipoproteins (LDL) and triglycerides are predictive factors for rapid, early and sustained virologic response in HIV/HCV co-infected patients treated with PegIFN/RBV

Insulin resistance (HOMA-IR>3) represents the key metabolic factor in lipid and glucose metabolism impairment related with HCV and HIV/HAART. HOMA-IR >3 impairs RVR,EVR and SVR.

LDL cholesterol level is usually lower in patients with viral hepatitis, in particular sustained by genotypes 2-3. Higher LDL level improves rapid virologic response in HV/HCV co-infected patients treated with PegIFN/RBV

High level of triglycerides could be related with booth insulin resistance and antiretrovirals lypodistrophic effect. Hypertriglyceridemia represents a negative predictor in rapid and early virologic response in HIV/HCV co-infected subjects.

Metabolic parameters have to be analysed and adjusted before to start treatment with PegIFN/RBV in HIV/HCV co- incfection.