1. BORDERNETwork Training on HIV and HBV Co-Infections Dr. med. Wolfgang Güthoff / Alexander Leffers, M.A. www.bordernet.eu www.aidshilfe-potsdam.de

2. This presentation arises from the BORDERNETwork project which has received funding from the European Union, in the framework of the Health Program, and co- funding of the Ministry of Environment, Health and Consumer Protection of the Federal State of Brandenburg. The sole responsibility of any use that may be made of the information lies with the authors (SPI, AIDS-Hilfe Potsdam e.V.)

3. Table of Contents Epidemiology HIV/HBV co-infection Diagnostic Treatment

4. HIV Infection and Chronic Hepatitis B Overlapping HBV and HIV Epidemics Hepatitis B HIV 350 Million Persons 35 Million Persons 3,5 Million Persons HIV/HBV co- infected

5. HIV Infection and Chronic Hepatitis B  HBV/HIV Co-infection prevalence depends on HBV epidemic  5 - 7% co-infections in low prevalence countries  10 - 20% co-infections in high prevalence countries  Despite ART - increasing risk of liver related death in this group  the natural course of HBV - infection in HIV/HBV co-infected patients is different

6. Increased Liver Mortality in HIV /HBV Co-infected Patients  Increased rates of chronic hepatitis after infection  Higher levels of HBVDNA viraemia  Faster progression to liver cirrhosis  Increased rate of liver cancer development

7. HIV / HBV Co-infection There are two main reasons for considering HBV therapy as a priority in HBV/HIV co-infected patients:  Liver disease may progress more rapidly in those patients and could lead to serious liver disease complications such as cirrhosis and liver cancer at younger ages.  There is a higher risk of developing hepatotoxicity following the initiation of antiretroviral therapy in HIV patients co-infected with HBV than in patients infected with HIV alone.

8. HIV / HBV Co-infection Because HIV infection can accelerate progression of liver disease, treatment of chronic hepatitis B is generally recommended in patients with:  HBV replication ( >2000 IU/ml )  Liver inflammation signs ( elevated ALAT )  Fibrosis ( liver biopsy Metavir 2, or high elastography )

9. HIV / HBV Co-infection Patients without ART indication:  use only substances without HIV activity (Peg Ifn, Adefovir, Telbivudine)  avoid Tenofovir, 3TC and FTC  avoid also Entecavir ( induction of HIV reverse transcriptase mutation M184V is possible )

10. Treatment of Hepatitis B in co-infected patients without ART indication Treatment with pegylated interferon should be considered in special circumstances:  HIV treatment is not needed (high number of CD4 cells)  HBe Ag positive  HBsAg genotype A  Elevated ALAT  Low level of HBVDNA ( poor data and no encouraging results )

11. Treatment of Hepatitis B in co-infected patients without ART indication Alternatively to peg. Interferon patients can be treated with HBV polymerase inhibitors:  Telbivudine  Adefovir  Telbivudine was preferred by most experts more than Adefovir (greater antiviral efficacy)  But always check possibility of early HAART including Tenofovir + FTC or 3TC (it is preferred - EACS 2011)

12. Treatment Algorithm for HBV in HIV Co-infected Patients HIV/HBV coinfection CD4 >500/µl or No indication of HAART CD4 <500/µl or symptomatic HIV or cirrhosis HBV Rx indicated (b) No HBV Rx indicated (b) Lamivudine experienced Lamivudine naive a)Early HAART including TDF + FTC/3TC® b)PEG-INF if genotype A, high ALT, low HBV DNA Monitor closely HAART including TDF ® + 3TC or FTC Add or substitute one NRTI with TDF ® as part of HAART Source: EACS 2011

13. HIV / HBV Coinfection - Treatment Algorithm for HBV in Patients with ART Indication for HIV treatment >2000 IU/µl HBV DNA Patients with cirrhosis Patients without HBV-associated 3TC resistance Patients with HBV- associated 3TC resistance HAART regimen of choice (in case of HBV polymerase inhibitor maintain full suppression) HAART including TDF + 3TC or FTC Substitute one NRTI with Tenofovir or add Tenofovir In case of liver decompensation refer for evaluation for LT <2000 IU/µl HBV DNA Source: EACS 2011

14. Treatment of HIV / HBV Co-infection Gold standard: ART contains Tenofovir +Emtricitabine or Lamivudine There is a problem in patients with virological failure to this first line ART:  if these patients are switched from Tenofovir / Emtricitabine to another drug, they will be vulnerable for hepatitis B liver inflammation flare Possibility: Continue Tenofovir and add Zidovudine

15. HIV / HBV Co-infection - Conclusions  Best solution: Early start of ART  If ART is not indicated: Limited treatment options with only Adefovir and Telbivudine  (Alternative Interferon)  Treatment of choice with patients on ART: Tenofovir  3TC or FTC mono-therapy should never be considered

16. HIV / HBV Co-infection - Conclusions Treatment of Hepatitis B follows the same rules as HIV:  full suppression of viral replication to avoid the development of drug resistance  successful therapy leads to inhibition of inflammation activity and reversion of fibrosis  final goal: immune control of infection

17. HIV / HBV Co-infection Don‘t forget:  HIV patients not infected with Hepatitis B should be vaccinated against HBV  successful response in 33% of patients with CD4 > 300/µl  successful response in 80% of patients with CD4 > 500/µl Rey D et al. Vaccine 18,116182000)