1. Overview of HCV and HBV co-
infections in patients with HIV in
Serbia
Jovan Ranin

2. Course of HIV
infection
HAART – Highly Active Anti-Retroviral
Therapy – dramatically changed the course of HIV
infection
art era HAART era
 high incidence of OI  lower incidence of OI
 the incubation period of 7 - 10  the incubation period of several
years decades
 short survival period  longer survival time
 high rate of morbidity and  improved quality of life
mortality
 comorbidities:
 poor quality of life
• metabolic diseases
• non-AIDS malignancies
• ESLD caused by HCV or/and HBV co-
infections

3. Importance of HCV and HBV co-
infections in patients with HIV
infection
1. similar mode of transmission longer survival with HAART
2. high rate of chronicity
high incidence of progression of co-infections
co-infections is more frequently
increased rate of morbidity and
mortality of ESLD in HIV infection

4. 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

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

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

7. 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

8. 1. before HAART
discriminators for groups of patients with HCV and HBV co-infections
compared with HIV mono-infection: immunological, epidemiological and
clinical features
2. one - year HAART
predictors of immunological, virological and clinical effects of HAART:
HCV and HBV co-infections
3. long - term HAART
predictors of immunological, virological and clinical effects of
HAART:
HCV and HBV co-infections

9. Prevalence of HCV and HBV
co-infection in studied
patients
N = 840
HIV/HBV HIV/HCV/HBV
HIV/HCV 4,5%
1,7%
23,9%
HIV
69,4%

10. Discriminators for patients with
HIV/HCV co-infection before HAART
negative discriminators positive discriminators
95% CI
gender OR
msm heterosex
0.070 2.525 hemophilia ivdu
0.276
10.079 30.295
3.807 transfusion
1.012 ALT
1.020 AST
1.775 CD4 < 100
CD4 baseline 0.997
1.660
AIDS
0.01 0.1 1 10 100
logistic regression univariate model

11. Discriminators for patients with HIV/HCV
co-infection before HAART
negative discriminators positive discriminators
gender 95% CI
6.851
OR
heterosex 9.500 hemophilia
0.113
1.735 AIDS
0.01 0.1 1 10 100
logistic regression multivariate model

12. Discriminators for patients with HIV/HBV
co-infection before HAART
negative discriminators
95% CI
gender
OR
0.079
ivdu
0.113
0.01 0.1 1
logistic regression multivariate model

13. Predictors for
immunological failure after
one year on HAART CD4 < 350
positive predictors
no significant:
HBV co-infection
HCV/HBV co-infection
AIDS
4.122
age
1.042
95% CI
HCV
1.580 OR
1 10
logistic regression multivariate model

14. Predictors for devoloping
of IRIS after one year on
HAART
IRIS – Immune Restoration Inflammatory
Syndrome
negative predictors positive predictors
no significant:
HBV co-infection
AIDS HCV/HBV co-infection
1.545
age
1.015
STI 0.554
95% CI
1.375 HCV HR
0.1 1 10
multivariate Cox proportional hazards regression model

15. Predictors for virological-
immunological success with long-
term HAART
success – und pVL and CD4 ≥ 350
negative predictors positive predictors
no significant:
AIDS
0.733
HBV co-infection
gender
STI 0.218
0.673
HCV/HBV co-infection
HCV 0.607
CD4 < 100 95% CI
0.563 HR
1.001 CD4 prim
0.1 1 10
multivariate Cox proportional hazards regression model

16. Causes of deaths of patients
with HIV infection in Serbia
N = 113
the mortality is 13.5 %
other
AIDS 33.6%
23.9%
non-AIDS Ca
15.0%
cardio 12.5% ESLD 15.0%

17. Predictors for deaths of patients
with HIV infection on long-term
HAART
negative predictors positive predictors
95%CI
HR
age
1.032 no significant:
gender 0.574
HBV co-infection
CD4 prim 0.998 HCV/HBV co-infection
2.081 HCV
0.1 1 10
multivariate Cox proportional hazards regression model

18. 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.

19. Conclusion
(II)

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

20. It is necessery to improve treatment
of HCV infection for patient with
HIV/HCV co-infection

21. Eternal struggle of these
three viruses
LIVE TOGETHER