jovan ranin - overview of HCV and HBV co-infections in patients with HIV in Serbia

Overview of HCV and HBV co-infections in patients with HIV

in Serbia

Jovan Ranin

high incidence of OI

the incubation period of 7 - 10 years

short survival period

high rate of morbidity and mortality

poor quality of life

lower incidence of OI

the incubation period of several decades

longer survival time

improved quality of life

comorbidities:

• metabolic diseases

• non-AIDS malignancies

• ESLD caused by HCV or/and HBV co-infections

art era HAART era

Course of HIV infectionHAART – Highly Active Anti-Retroviral

Therapy – dramatically changed the course of HIV infection

1. similar mode of transmission

2. high rate of chronicity

high incidence of co-infections

longer survival with HAART

progression of co-infections is more frequently

increased rate of morbidity and mortality of ESLD in HIV infection

Importance of HCV and HBV co-infections in patients with HIV infection

Prevalence of HCV and HBV co-infections in the world

number of cases

•HIV – 33 million (60 million) 1

•HCV – 170 million 2

•HBV – 500 million 3

prevalence of HCV and HBV co-infections

•HIV/HCV – 15 – 33 % 4

•HIV/HBV – 6 – 14 % 5 • up to 90 % of HIV patients are seropositive for HBV antibodies 5

1 Del Rio C PPID 2010; 2 WHO 2007; 3 Koziel MJ PPID 2010; 4 Alberti A J Hepatol 2005; 5 Alter MJ J Hepatol

2006

HIV infection 1, 2

• increased the frequency of viral persistence after acute infection

•higher level of HCV RNA in peripheral blood

•more frequently reappearance of HBV markers

• faster progression to cirrhosis

•higher prevalence of devolopment of ESLD and HCC

•higher rate of mortality HAART 3, 4

•hepatotoxicity of HIV drugs

•“flare” of HCV or HBV infection - IRIS

• immune reconstitution improve surveillance of HCV and HBV co-infections

Impact of HIV infection and HAART on the course of HCV and HBV co-infections

1 Goedert JJ i sar J Infect Dis 2000; 2 Goedert JJ i sar Blood 2002; 3 Qurishi N i sar Lancet 2004; 4 Mehta SH i sar Hepatology 2005

remains unclear controversial results of the studies

• interfere with immune reconstitution induced by HAART 1

•no influence on immune reconstitution 2

• interfere with immune reconstitution, but without influence on progression of HIV infection to AIDS 3

•no impact on rate of mortality in patients with HIV infection 3

• interaction with HAART 4

• decreased drug metabolism

• decreased HCV – specific immune reconstitution

• increased susceptibility to mitochondrial dysfunction

Impact of HCV and HBV co-infections on the course of HIV infection

1 Greub G i sar. Lancet 2000; 2 Sulkowski MS i sar. JAMA 2002; 3 Sullivan PS i sar. AIDS 2006; 4 Wit FW i sar. J Infect Dis 2002

Design of study

longitudinal cohort study

840 patients with HIV infection were followed

study period was 1997 – 2010

patients were included into the study until June 2009

mean time of follow-up was 71,9 ± 42,2 months

inclusion criteriums:

• HIV infection diagnosed accordingly with CDC clasification system from 1993 and revised in 2008

• using HAART

logistic regression and Cox proportional hazards regression models within SPSS

three parts of study

before HAART

one - year HAART

long - term HAART

1.

2.

3.

discriminators for groups of patients with HCV and HBV co-infections compared with HIV mono-infection: immunological, epidemiological and clinical features

predictors of immunological, virological and clinical effects of HAART:

HCV and HBV co-infections

predictors of immunological, virological and clinical effects of HAART:

HCV and HBV co-infections

HIV

69,4%

HIV/HCV/HBV

1,7%HIV/HCV

23,9%

HIV/HBV

4,5%

Prevalence of HCV and HBV co-infection in studied patients

N = 840

1.020

1.012

0.997

0.2760.070 2.525

30.29510.079

3.807

1.775

1.660

0.01 0.1 1 10 100

95% CI

ORgendermsm heterosex ivduhemophilia

transfusion

CD4 < 100AIDS

ALT AST

CD4 baseline

negative discriminators positive discriminators

Discriminators for patients with HIV/HCV co-infection before HAART

logistic regression univariate model

Discriminators for patients with HIV/HCV co-infection before HAART

logistic regression multivariate model

6.851

0.113

9.500

1.735

0.01 0.1 1 10 100

95% CI

OR

gender

hemophiliaheterosex

AIDS

negative discriminators positive discriminators

Discriminators for patients with HIV/HBV co-infection before HAART

0.113

0.079

0.01 0.1 1

95% CI

ORgender

ivdu

negative discriminators


Predictors for immunological failure after one year on HAART


4.122

1.580

1.042

1 10

95% CI

OR

AIDS

age

HCV

positive predictorsno significant:

HBV co-infection

HCV/HBV co-infection

CD4 < 350

Predictors for devoloping of IRIS after one year on HAART

1.545

0.554

1.375

1.015

0.1 1 10

95% CI

HR

negative predictors positive predictors

AIDS

age

STI

HCV

multivariate Cox proportional hazards regression model

no significant:

HBV co-infection


IRIS – Immune Restoration Inflammatory Syndrome

Predictors for virological-immunological success with long-term HAART

0.733

0.218

0.563

0.673

1.001

0.607

0.1 1 10

95% CI

HR



AIDS

genderSTI

HCV

CD4 < 100

CD4 prim

no significant:

HBV co-infection


success – und pVL and CD4 ≥ 350

other

23.9%AIDS 33.6%

non-AIDS Ca

15.0%ESLD 15.0%cardio 12.5%

Causes of deaths of patients with HIV infection in Serbia

N = 113

the mortality is 13.5 %

Predictors for deaths of patients with HIV infection on long-term HAART

1.032

0.574

2.081

0.998

0.1 1 10

95%CI

HR

age

CD4 prim

HCV

gender



no significant:

HBV co-infection


Conclusion (I)

prevalence of HCV and HBV co-infection in Serbia • similar as in other Europian countries

• HCV – 23,9 %

• HBV – 4,5 %

• HCV/HBV – 1,7 %

mortality of HIV patients in Serbia• mortality is 13,5 %

• ESLD caused 15 % of deaths which is higher rate compared with era before HAART (12 %) 1

• HCV co-infection is predictor for mortality, while HBV co-infection is not associated with risk for death

1 Brmbolić B. Phd 1992.

HCV co-infection • intensify CD4 limfopeny in natural history of HIV infection

•cause faster progression of natural history of HIV infection to AIDS

• interfere with immune reconstitution in first year of HAART

•provocate devolopment of IRIS

•cause immunological-virological failure of long-term HAART

•has negative effect on survival of patient with HIV infection

HBV co-infection

• it is not associate with immunological, virological and clinical characteristics of simultaneous HIV infection

Conclusion (II)

It is necessery to improve

treatment of HCV infection for

patient with HIV/HCV co-infection

Eternal struggle of these three viruses

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jovan ranin - overview of HCV and HBV co-infections in patients with HIV in Serbia

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