BORDERNETwork Training on

HIV and HBV Co-Infections Dr. med. Wolfgang Güthoff / Alexander Leffers, M.A.

www.bordernet.eu

www.aidshilfe-potsdam.de

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.)

Table of Contents

Epidemiology

HIV/HBV co-infection

Diagnostic

Treatment

HIV Infection and Chronic Hepatitis B

Overlapping HBV and HIV Epidemics

Hepatitis BHIV

350 Million Persons

35 Million Persons

3,5 Million Persons HIV/HBV co- infected

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

> 8 % High

< 2 % Low 2 - 8 % Intermediate

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

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.

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 )

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 )

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 )

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)

Treatment Algorithm for HBV in HIV Co-infected Patients

HIV/HBV coinfection

CD4 >500/µl orNo 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 closelyHAART including TDF ® + 3TC or

FTC

Add or substitute one NRTI with TDF ® as part of HAART

Source: EACS 2011

HIV / HBV Coinfection - Treatment Algorithm for HBV in Patients with ART

Indication for HIV treatment

>2000 IU/µl HBV DNAPatients 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

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

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

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

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

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)