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1
Triglycerides,LDL cholesterol and HOMA score
predict the virological response in HIV/HCV
co-infected patients treated with Pegylated
interferon alpha 2a and Ribavirn
Paola Nasta MD Institute of Infectious and
Tropical Diseases University of Brescia P.Le
Spedali Civili, 1 25123 Brescia, ITALY Tel
39-030-3995665 E-mail paola.nasta_at_tin.it
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.
Institute of Infectious and Tropical Diseases,
University of Brescia, Italy
Results
Background
Variables correlated with Rapid (RVR), Early
(EVR) and Sustained (SVR) virologic response

• 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

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 gt 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) lt0,001 0,05(0,007-0,3) 0,001 19(32,2) lt0,001 0,04(0,009-0,2) lt0,001 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 lt400.000 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 gt 200 mg/dl n() Chol LDL mg/dl M (SD) Median (IQR) Chol HDL mg/dl M (SD) Median (IQR) Chol HDL lt40 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 gt 150 mg/dL n() 145 (87,6) 125 (82-181) 34(35,4) 112(52) 6(14,6) 0,0004 lt0,001 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 lt 3 n () 35 (46,1) 25(62,5) lt0,001 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
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

CONCLUSIONS

• Metabolic parameters as insulin resistance
  (HOMA gt3), 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-IRgt3) represents the
  key metabolic factor in lipid and glucose
  metabolism impairment
• related with HCV and HIV/HAART. HOMA-IR gt3
  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.

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 Fishers exact test Variables
possibly associated with RVREVR, SVR
achievement were evaluated using the logistic
regression model. Analyses were performed using
Epi InfoTM version 3.3.2 (February 9,2005)