Transcript Session 16 - Teaching Slides

Hepatitis B and Hepatitis C
in Patients with HIV
Infection
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
1
Learning Objectives
By the end of this session, participants
will be able to:
 Explain how liver disease affects PLHIV
 Explain the mechanics of HIV/HBV and
HIV/HCV interactions
 Describe how to prevent HBV and HCV
 Explain treatment options for HIV/HBV
and HIV/HCV co-infection
2
Mortality (%)
Mortality from End-stage Liver Disease as a
Percentage of all Deaths Among HIV Patients
60
Pre-ART era
50
ART era
40
35%
50%
45%
30
20
13%
10
0
12%
5%
Italy
(Brescia)
Spain
(Madrid)
USA
(Boston)
3
Hepatitis B Virus (HBV)
4
HBV Basics


Hepatitis B is a
viral infection that
attacks the liver
It can cause both
acute and chronic
disease

Symptoms of acute
infection include:
• yellowing of skin and
eyes (jaundice)
• dark urine
• extreme fatigue
• nausea, vomiting
• abdominal pain

Chronic liver infection
can lead to:
• liver fibrosis (cirrhosis)
• liver cancer
5
HBV Transmission
Infected
Person
IDU/Blood
Unsafe Sex
Occ. Exposure
Infected
Mother
Infected Adult
30-50%
symptomatic
0.5-1%
mortality
Infected
Baby
(< 10%
symptomatic)
90%
Resolve
Infection
5-10%
90%
Chronic
Infection
Global Epidemiology of HBV
2 billion HBV
infections
6 billion people
in the world
25% mortality from
HCC or cirrhosis
300–400 million
chronic HBV
7
Global Epidemiology of Chronic HBV
HBsAg prevalence
> = 8% - High
2% - 8% - Medium
< 2% - Low
8
Epidemiology of HBV Infection
in Vietnam


Vietnam is a country with a high
prevalence (>8%) of chronic HBV
HBV prevalence (HBsAg+) in
different populations includes:
• General population: 10-20%
• Healthcare workers: 8-18%
• HIV +: 10-15%
Nguyen TTM. Liver International 2008
Nguyen TC. CROI Abstract 2010
9
HBV Prevention



HBV is preventable with a safe, effective
vaccine
All infants should receive HBV vaccine series
Adults in high risk groups should also be
vaccinated, including:
• persons with high-risk sexual behavior
• partners and household contacts of HBV
infected persons
• injecting drug users
• HIV-infected patients
• Health care workers
Have you been vaccinated?
10
HBV Diagnosis
HBsAg
AntiHBs
AntiHBc
IgM
AntiHBc
Interpretation
-
-
-
Susceptible
-
+
+
Immune due to
natural infection
-
+
-
Immune due to
vaccination
+
-
+
+
Acutely infected
+
-
+
-
Chronically
infected 11
HBV/HIV Interaction

Compared to HIV- individuals, patients
with HIV and HBV are more likely to:
• Develop chronic infection (21% vs. 7%)
• Be “e antigen” positive and have higher
levels of HBV DNA
• Experience faster progression of liver
disease with increased rates of cirrhosis
and liver cancer

HBV does not appear to affect
progression of HIV infection
12
HIV/HBV Treatment (1):
When to Treat

Treatment of chronic HBV in a PLHIV
is indicated when:
• HIV treatment is indicated
AND / OR
• HBV treatment is indicated
13
HIV/HBV Treatment (2):
Criteria for HBV Treatment

Elevated HBV DNA and elevated ALT
HBeAg
positive
HBeAg
negative
•
•
•
•
HBV DNA
ALT > 2X
HBV DNA
ALT > 2X
> 20,000 IU/ml and
normal
> 2,000 IU/ml and
normal
Presence of HBsAg and repeatedly
elevated liver enzymes suggests active
disease and need for HBV therapy
14
Dose
HBV Treatment Drug
Lamivudine 100 mg/day (HBV
Options
mono-infection)
(3TC,
Epivir)

3TC, TDF,
Entecavir
have activity
against both
HIV and HBV
300 mg/day (HIV coinfection)
Tenofovir
(TDF,
Viread)
300 mg/day
Adefovir
(Hepsera)
10 mg/day
0.5 mg/day
Entecavir
(Baraclude) 1 mg/day if 3TC
resistant
Telbivudine 600 mg/day
Peg180 mcg SQ/wk
Interferon
HIV/HBV Treatment Options (1)
Indication
Treatment
If HIV treatment
is indicated
Start ART and include anti-HBV
drugs (TDF+3TC)
If HIV treatment
is not indicated
and HBV
treatment is
indicated
Consider early ART and include
anti-HBV drugs (TDF+3TC)
or
Treat with anti-HBV drug (without
ART) that has no effect against
16
HIV
HIV/HBV: Treatment Options (2)
These drugs also
fight/treat HIV:
Drugs that do not
work against HIV:

Lamivudine

Adefovir

Tenofovir

Telbivudine

Entecavir

Interferon-alpha

Do not use as
monotherapy for HBV
due to risk of HIV
developing resistance

OK to use as
monotherapy for
HBV: no risk of HIV
resistance to ARV
17
ART Drug Selection for HIV/HBV
Co-Infection

TDF and 3TC for all patients with
HIV/HBV co-infection
• Work against both HIV and HBV
• High rate of HBV drug resistance if 3TC
alone is used

Efavirenz preferred over Nevirapine
• Due to risk of hepatotoxicity

In Vietnam, preferred 1st line
regimen is TDF + 3TC + EFV
18
HIV/HBV Treatment Algorithm
HBsAg Positive
Meets criteria for ART according to
MOH guidelines?
No
Yes
Meets criteria
for HBV
treatment?
Start ART
TDF+3TC+EFV
Yes
Consider early ART
No
Reassess need for HIV
and/or HBV treatment
every 3-6 months
Clinical Consideration: HBV
Flares on ART


HBV flare: rapid increase in liver
enzyme levels, with signs and
symptoms of hepatitis
Caused by:
• Immune reconstitution inflammatory
syndrome (IRIS)
• Discontinuation of anti-HBV drugs (3TC,
TDF) when ART is stopped
• Development of resistance to anti-HBV
drugs
20
Clinical Consideration: HBV
Flares and IRIS




HBV flares secondary to IRIS - first few
months of treatment
Can be difficult to distinguish from ARTinduced hepatic toxicity
Drugs active against HBV should be
continued during a suspected flare
If no way to distinguish serious HBV
flare from grade 4 ART toxicity, then
withhold all ARV drugs until condition
improves
21
HBV Flares When ART is
Stopped

Stopping anti-HBV drugs in a patient
with HIV/HBV can lead to severe
HBV flares
• Fatal cases of acute HBV have occurred
in this setting

HIV/HBV patients who need to stop
the HBV-active drugs in the HIV
treatment regimen (3TC, FTC or
TDF) should be monitored closely
22
Hepatitis C Virus (HCV)
23
HCV Basics


Hepatitis C is a viral infection that
attacks the liver
Like HBV, it can cause both acute
and chronic disease.
• Most patients have mild or no
symptoms at the time of infection but
go on to have chronic life-long infection

There are 6 genotypes of HCV
• Genotype affects treatment response
24
HCV Transmission
25
Source: WHO 1999
HCV: A Global Health Problem
170 Million Carriers Worldwide, 3-4 MM new cases/year
FAR EAST ASIA
60 M
WEST
EUROPE 9 M EAST
MEDITERRANEAN
20M SOUTH EAST
ASIA
30 M
AFRICA
32 M
U.S.A.
4M
SOUTH
AMERICA
10 M
AUSTRALIA
0.2 M
HCV Prevalence in Vietnam



General population: 1-5%
Hemodialysis patients: 54%
IV drug users: 60-90%
Nakata S: J Gastroenterol Hepatol. 1994 Jul-Aug;9(4):416-9.
Nguyen VTT. Hepatol Int (2007) 1:387–393
27
HCV Prevention

No currently available medications or
vaccines are protective against HCV
infection
28
HCV Progression (1)



Rarely fulminant and fatal
Acute infection causes symptoms in
<20%
After acute infection:
• 15% clear virus from blood and have
full recovery
• Other ~ 85% have viremia that persists
for life

Seroconversion may take 3 months
29
HCV Progression (2)
Chronic HCV
Infection
20
years
Annual rate
Factors that
Speed HCV
Progression:
• HIV
• HBV
• Alcohol
• Male sex
• Age > 40
Cirrhosis 20 %
Decompensation
6%
HCC
4%
Death
4%
Hoofnagle, Hepatology, 1997; Di Bisceglie, Hepatology, 2000
Clinical Course of HCV

Disease progression cannot be
predicted by laboratory tests
• Pattern of ALT elevation does not
correlate well with disease outcome
• Neither does HCV RNA (viral load)

Liver biopsy the best predictor of
disease course
31
HIV/HCV Interaction
Effects of HIV
on HCV



Faster progression to
fibrosis, liver failure
and liver cancer than
patients with HCV
alone
Higher HCV viral loads
Higher rate of MTCT of
HCV
Effects of HCV
on HIV


No effect on natural
progression of HIV,
but
Increased risk of
hepatotoxicity from
ARV
32
HCV Treatment: Indications






Positive HCV RNA
Persistent  ALT
Liver biopsy with fibrosis and at least
moderate inflammation
Stable HIV infection
No contraindications for use of PEGinterferon or ribavirin
Treatment available
33
HCV Treatment: Regimen
Drug
Dosing
Pegylated
Interferon
alpha
α2a: 180 mcg SQ
once per week
Ribavirin
Common Side
Effects
• Myelosuppression
• Depression
• Myalgias
α2b:1.5 mcg/kg SQ • Fevers
once per week
PLUS
800-1200 mg daily • Hemolytic anemia
• Teratogenicity
• Duration: 48 weeks
• Response rates vary by genotype
HIV/HCV Treatment:
Considerations
Combination
Risk
Ribavirin and ddI
Increased risk of
combination
mitochondrial toxicity
contraindicated
(pancreatitis, lactic acidosis)
Avoid Ribavirin and AZT if Increased risk of anemia
possible
EFV and Interferon can
Increased risk of
be used together but:
neuropsychiatric side effects
Interferon therapy is associated with a
decline in CD4 count (CD4% not affected)
35
HCV Treatment Algorithm for
HIV/HCV Co-infection
Decision made to treat patient based on clinical and laboratory data
Initiate pegylated interferon + ribavarin
Obtain quantitative HCV RNA after 12 weeks of therapy
HCV RNA undetectable or
detectable with
≥ 2 log10 reduction
HCV RNA detectable with
< 2 log10 reduction
Reassess HCV RNA
at 24 weeks
Stop Therapy
HCV RNA undetectable
No
Stop Therapy
Yes
Complete 48 weeks of therapy
HIV/HCV: Important
Recommendations


Abstain from all alcohol intake
Vaccinate against HAV and HBV, if
not immune already
37
Case Study
38
Key Points




HBV and HCV are both prevalent in
Vietnam
HIV accelerates HBV and HCV induced
liver disease
HBV/HIV can both be treated with ARV
using tenofovir and lamivudine
In Vietnam, most patients do not have
access to HCV treatment
• important to minimize liver damage by
avoiding alcohol
39
Thank You
Questions?
40