Viral Hepatitis Prevention Board Meeting€¦ · 3 041 13 147 Female Male CVEDT 30 ‐ 09 ‐ 2010....

Viral Hepatitis Prevention Board Meeting

Epidemiology of coinfection (HIV, HCV) in Portugal

Rui Sarmento e Castro

Infectious Diseases Depart., Hosp. Joaquim UrbanoHealth Sciences School, University Minho Portuguese Study Group on Coinfection, PresidentLisbon, 19 Nov 2010

Burden and Prevention of Viral Hepatitis in Portugal

0

500

1000

1500

2000

2500

3000

83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

3 6 41 78156

258369

522664

9481040

1314

1656

2131

2444

26242764 2763

24262334

21582081

1902191518621820

1398

116

AC (n = 18 182)

ARC (n = 3 739)

AIDS (n = 15 872)

CVEDT 31‐03‐2010N = 37793

Num

ber of cases

PORTUGAL HIV and AIDS cases reported by year and stage of infection

Year of diagnosis

3 041

13 147

FemaleMale

CVEDT

30‐09‐2010

81,2%

18,8%

PORTUGAL AIDS cases by gender

0

1000

2000

3000

4000

5000

6000

7000

< 1 1 a 4 5 a 14 15 a 24 25 a 34 35 a 44 45 a 54 55 a 64 > 64

52 32 47

1410

6227

4733

2142

996

483

AgeCVEDT

30‐09‐2010

PORTUGAL AIDS cases by age

CVEDT 30‐09‐2010

PORTUGAL

AIDS cases by transmission category

0

1000

2000

3000

4000

5000

6000

7000

8000

MSM IVDU MSM‐IVDU Transf‐Hemof Hetero M/Child Unknown

2012

7390

123 199

6001

101363

Total = 16 189

34,0

36,542,1

45,2

50,7

45,9

50,6

59,756,9

59,6

7,6 6,3 7,08,4 7,6 7,9 9,2 8,7

12,013,1

55,954,0

48,7

43,7 43,2 44,0 38,3

30,127,4

23,6

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

HETERO

MSM

IVDU

PORTUGALNew AIDS cases: trends by transmission category

%

Year of diagnosis CVEDT 31‐12‐2009

PORTUGALAIDS cases: death by transmission category

0

500

1000

1500

2000

2500

3000

3500

4000

1084

3259

66 112

1556

15207

0

523

0 33

565

20 35

1084

3782

66 145

2121

35242

MALE

FEMALE

ALL

CVEDT 31‐12‐2009N = 7475

PORTUGALAIDS cases: mortality by opportunistic disease

CVEDT 31‐03‐2010

6809

2563

745

4236

567139

372165 198

21 57

3108

1210

489

1926

276 94 21784 115 3 9

0

1000

2000

3000

4000

5000

6000

7000

8000

Cases

Deaths

Regions:SouthCentralNorthEast

South: 695 = 41.4 %

North: 359 = 23.2 %

Central: 293 = 19.6 %East: 613 = 46.9 %

Rockstroh et al. J Inf Dis 2005;192:992–1002

Prevalence of hepatitis C in the HIV population (1960/5957 patients = 33%)

• Estimated HCV prevalence: 1.0 to 1.4% 100.000-140.000

Rui Tato Marinho, DGS

• Number of reported cases of HIV Infection: 38.000CNLCS, 2009

• Estimated prevalence in the South of Europe: 41.4%Eurosida, 2005

• Estimated number of coinfected patients (HCV/HIV): 15.732

Epidemiology of HCV in Portugal

• AIM and Methods• Evaluation of differences between HIV negative and HIV positive

patients infected with HCV

• Retrospective, transversal, multicentric survey• Participation of 10 hospitals (ID, IM, Gastroenterology)

Monoinfected 783 pts Coinfected 1650 pts

Epidemiology of HCV in Portugal

HCV monoinfected versus HCV /HIV coinfected patients

Organized by the Portuguese Study Group on HIV/Hepatitis coinfection

Data were analyzed for statistical significance by student t test or non parametric test

HCV/HIV- HCV/HIV+ TOTALMale 627 (80.1%) 1294 (78.4%) 1952 (78.7%)

Female 156 (19.9%) 356 (21.6%) 512 (21.0%)Mean age, ♂ 39.8 years 39.3 years 39.5 years Mean age, ♀ 42.3 years 37.1 years 38.8 years

HCV monoinfected versusHCV/HIV coinfected patients

Transmission

IVDU Sexual Transfusion Unknown

78.8% (1955)

9.3% (231) 2.3% (58) 7.8% (193)


Transmission by HIV status

5.4%

HIV ‐ HIV +


IVDUUnknowTransfSexual

IVDUUnknowTransfSexual


54,0% 1,5% 25,9% 18,4% 0,2% 0,0%0,0%

10,0%

20,0%

30,0%

40,0%

50,0%

60,0%

1 2 3 4 5 6

Genotype distribution

N = 542

Genotype

N = 1130 N = 32 N = 384 N = 4 N = 1

Freq

uency

HCV/HIV - HCV/HIV+ TOTALHCV Genotype 1 384 (52.7%) 728 (54.9%) 1112 (54.0%)HCV Genotype 2 12 (1.6%) 20 (1.5%) 32 (1.5%)HCV Genotype 3 209 (28.7%) 321 (24.2%) 530 (25.9%)HCV Genotype 4 123 (16.9%) 255 (19.3%) 378 (18.4%)


52,70%

1,60%

28,70%

16,90%

54,90%

1,50%

24,20%

19,30%

0%

10%

20%

30%

40%

50%

60%

HCV Genotype 1 HCV Genotype 2 HCV Genotype 3 HCV Genotype 4

HCV/HIV ‐

HCV/HIV+

Distribution of genotype by gender and mode of transmission

Gender Mode of transmission


Genotype Genotype

IVDUSexual

RiskSex

Genotype distribution by HIV status and gender

HIV negative HIV positive

P = 0.03

Genotype Genotype


BASELINE ALT BY GENOTYPE, HIV STATUS AND CD4 CELLS

p<0.0001 P<0.001 p=0.05

n=908

n=29

n=436

n=313

n=740

n=1235

n=444

n=274

n=229n=177

n=63


HCV VIRAL LOAD BY GENOTYPE, HIV STATUS AND CD4 CELLS

p=ns (0.795) p<0.001 p=ns (0.244)

n=892

n=24

n=431 n=311

n=702

n=1132

n=422n=259

n=210

n=152

n=44


Genotype CD4 cellsHIV neg (n=702) HIV + (n=1132)

Main reasons to treat chronic HCV in HIV-infected patients

HIV patients live longer

HIV increases viral load of HBV and HCV

Faster progression to liver cirrhosis1

Increased mortality due to end-stage liver

disease (ESLD)2

Higher risk of hepatotoxicity following treatment with

antiretroviral therapy (ART) drugs

1. Poynard et al. J Hepatol 2003;38:257–65; 2. Rosenthal et al. J Viral Hepatitis 2007;14:183–188

CD4+ T cells count <200/mm³ 26,8% (n=30) Precarious socioeconomic conditions 3,6% (n=4)

Severe psychiatric disease* 17,9% (n=20) Patient refusal 2,7% (n=3)

Chronic alcohol abuse 16,1% (n=18) Recent immunological recovery 1,8% (n=2)

Active intravenous drug use 14,3% (n=16) Active opportunistic infections / Infectious diseases 2,7% (n=3)

Previous unsuccessfull HCV treatment 10,7% (n=12) Absence of liver biopsy 3,6% (n=4)

Nonadherence with medical visits 8,9% (n=10) Decompensated hepatic cirrhosis 1,8% (n=2)

Thrombocytopenia <70 000 7,1% (n=8) Concomitant medication with rifampin/rifabutin, isoniazide, pyrazinamide

2,7% (n=3)

Serum creatinine level >1,5x ULN 2,7% (n=3) Anatomic splenectomy 0,9% (n=1)

Hgb<12(M) ou <11 (F) [mg/dl] 1,8% (n=2) Pregnancy 0,9% (n=1)

Age >50 years 2,7% (n=3) Nonadherence to HAART 3,6% (n=4)

Severe pulmonary disease 0,9% (n=1) Unidentified reasons 11,6% (n=13)

Only 10‐15% of HCV/HIV co‐infected patients were treated

Reasons for non‐treatment of chronic hepatitis C in HIV infection

Marques, N. 3rd Internat. Workshop on HIV and Hepatitis. Paris 2007

Treatment of coinfection in Portugal

39,5

20 18,3

5,2

11,5

Patient desire Concomitant disease

Drug abuse Decompensated liver disease

Other

Barriers to HCV Antiviral Treatment Among IDUs

Patient desire = fear of therapy and lack of understanding regarding importance of therapy

Zehnter E et al. AASLD 2007. Abstract 276

Barriers to HCV Antiviral Treatment Among IDU

• Concern side effects

• Don’t feel sick

• Other health problems

• Don’t want to make liver biopsy

• Inadequate information

• Length of treatment

Clinical decision based inprobable lower adherence in IDUs

47,0%

53,0%

HIV POS

RVS

NO


Sustained Virological Response

69,3%

30,7%

HIV NEG

62 % Genotype 1 25.9%84% Genotype 3 78%

n = 296 n = 290

Deaths in a cohort of 23,441 HIV patientson antiretrovirals

Weber et al. Liver-related deaths in persons infected with HIV: the D:A:D study. Arch Intern Med 2006; 166: 1632-41.

• Hep B, C, D• Drug-related toxicity

0

5

10

15

20

25

30

35

HCVTotal

0

5

10

15

20

25

HCVTotal

Causes of Death in 2000 and 2009 in HIV-infected PatientsAdmmitted in ID Service (HJU)

N = 52 HCV/HIV 71%

2000 2009

N = 43HCV/HIV 70%

CONCLUSIONS

The prevalence of HCV in the HIV-infected population ishigher than 40%

The number of new cases of HCV/HIV coinfection isdecreasing in recent years

Male/female ratio in coinfected patients is ≈ 4:1

Mean age of coinfected patients is, at the moment of diagnosis, 38-39 years

IVDU is the most important mode of acquisition of bothviruses


In patients infected with genotype 3 mean baseline ALT values were higher than in patients with other genotypesBaseline ALT values were lower in coinfected versusmonoinfected patientsIn coinfected patients ALT levels were directely associatedwith CD4 cell count

CONCLUSIONS

Genotype 1 (55%) and genotype 3 (26%) are the mostprevalent genotypes in coinfected patientsGenotype 4 (18.5%) is also relevant is this population


CONCLUSIONS

Mean baseline HCV viral load was higher in coinfectedpatients when compared with monoinfected

In coinfected patients, HCV viral load was inverselyassociated with CD4 cells count

SVR was lower in coinfected patients with genotype 1 (when compared with monoinfected patients) butresponse to treatment was good in patients withgenotype 3

All efforts must be done to treat coinfected patients toprevent the rising mortality registered in this population


• Hospital Joaquim Urbano– Tavares AP– Méndez J– Sarmento e Castro

• Hospital Egas Moniz– Borges F– Alfaiate D– Mansinho K

• Hospital de Santa Maria– Badura R– Valadas E– Afonso C– Santos C– Janeiro N– Antunes F

• Centro Hospitalar de Coimbra– Valente C– Vieira A– Faisca R

AKNOWLEDGMENTS

• Hospital Curry Cabral– Machado J

– Maltez F

• Hospitais da Universidade de Coimbra– Alves H

– Serra E

– Saraiva Cunha J

• Hospital São João– Serrão R

– Sarmento A

• Hospital Garcia de Orta– Aguas MJ

– Azuaje C

• Hospital Vila Real– Presa J

• Centro Hospitalar Lisboa Central– Lampreia F

– Germano I

– Calinas F

– Corte Real R

Viral Hepatitis Prevention Board Meeting€¦ · 3 041 13 147 Female Male CVEDT 30 ‐ 09 ‐ 2010....

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