Transcript HIV and Hepatitis Co

HIV and Hepatitis Co-infection
Lucille Sanzero Eller, PhD, RN
Associate Professor
Rutgers, The State University of New Jersey
College of Nursing
A Local Performance Site of the NY/NJ AETC
September 2009
Objectives (1)
1. Describe transmission, signs and
symptoms of Hepatitis A.
2. Describe transmission, signs and
symptoms, testing, and treatment of
Hepatitis B.
Objectives (2)
3. Describe transmission, signs and
symptoms, testing, and treatment of
Hepatitis C.
4. Discuss education of HCV infected patient.
Viral Hepatitis

Viruses that cause hepatitis include
hepatitis A, B, C, D, E, F and G.

Over 90% of hepatitis is caused by viruses
A, B or C.
Hepatitis A Virus (HAV)
Transmitted through contact with fecal
matter containing the virus
 Causes acute hepatitis; symptoms include

– fever
– malaise
– anorexia
– nausea
– abdominal pain
– dark urine
– jaundice
Hepatitis A Virus (HAV)
 Signs
and symptoms usually last <2
months
 10%
to 15% of those infected have
prolonged or relapsing disease (lasts
6-9 months)

Once recovered, those who have
had HAV are immune to the disease
Hepatitis B Virus (HBV) (1)

Most common hepatitis virus

A DNA virus from the Hepadnaviridae family

Transmitted through exposure to infected
blood and body fluids
– perinatal
– percutaneous
– sexual
Hepatitis B Virus (HBV) (2)
Replication begins with attachment to
hepatocytes
 Covalently closed circular DNA (CCCDNA),
the template for the eventual production of
new virus particles, is synthesized
 HBV can evade the innate immune
response; HBV specific T-cells and trace
amounts of HBV DNA in hepatocytes persist
many years after recovery from acute HBV

Hepatitis B Virus (HBV) (3)

Symptoms occur in about 70% of patients
within 9-21 weeks after exposure to HBV,
and include
– fever
– malaise
– anorexia
– nausea
– abdominal pain
– dark urine
– jaundice
Hepatitis B Virus (HBV) (4)

Chronic HBV infection (5-10% of those
infected) can cause cirrhosis, hepatocellular
carcinoma (HCC), and liver failure

The CDC estimates that 1.25 million people
in the United States are infected with HBV

HBV vaccine, available since 1982, is
recommended for all age groups to
prevent HBV
HIV/HBV Co-infection

Those co-infected 3 to 6 X more likely to develop
chronic HBV than if monoinfected with HBV.

Since HBV genetic material remains in human
cells, the virus may be reactivated as immune
function deteriorates.

About 25% of people with chronic HBV develop
liver damage including cirrhosis or HCC; rate of
liver damage is higher and hepatitis B disease
progression is more rapid in those with HIV/HBV.
Hepatitis C Virus (HCV) (1)
A single-stranded ribonucleic (RNA) virus
 Flaviviridae family
 6 major subtypes; with genotype 1
responsible for more than 70% of infections
in U. S.
 Most common bloodborne infection in the
U.S.
 There is no vaccine for HCV

Hepatitis C Virus (HCV) (2)
1.8% of Americans (3.9 million) infected with
HCV; most (2.7 million) are chronically
infected (50-80% of those infected) (CDC, 2006)
 Prevalence estimated from the third National
Health and Nutrition Examination Survey

– civilian, non-institutionalized U.S. population

NHANES III survey did not include
incarcerated, homeless
– these groups have high prevalence of HCV, so
estimate is conservative
Hepatitis C Virus (HCV) (3)
 80%
of those infected are
asymptomatic

50-80% of immunocompetent people
who become infected become
chronically infected
Hepatitis C Virus (HCV) (4)

Among the chronically infected
– 60% to 70% develop chronic hepatitis
– 10% to 20% develop cirrhosis over a
period of 20-30 years
– 1% to 5% develop HCC
– End-stage liver disease (ESLD) and HCC
cause between 10,000 and 12,000 deaths
per year in the U.S.
Sources of Infection with HCV (1)
(CDC, 2006)
Sources of Infection with HCV (2)

60% of cases due to past or current IDU

60% to 80% of IDUs injecting drugs for at least 5
years are HCV infected vs. 30% of them HIV
infected

Risk of HCV transmission through sexual
exposure is low
 However, general population’s frequency of sexual
behaviors, plus prevalence of HCV, explains the high
proportion (15%) of HCV transmitted through sexual
exposure
Sources of Infection with HCV (3)

10% due to transfusion (prior to screening)
 Viral inactivation techniques for clotting factors
introduced in 1985 (Factor VIII); 1987 (Factor IX)

By 2001, risk of infection from a unit of
transfused blood less than one per million
transfused units

Currently, all immune globulin products
undergo a virus inactivation procedure or
test negative for HCV prior to release
Sources of Infection with HCV (4)

5% of cases due to
 exposures from hemodialysis
 employment in the health care field
 birth to an HCV-infected mother

10% of cases have no recognized source of
infection
HIV/HCV Co-infection (1)

HIV increases the levels of HCV viremia and
progression to cirrhosis, liver failure and
death

Risk of liver-related mortality in the coinfected is related to HIV viral load and CD4
count
HIV/HCV Co-infection (2)


Study compared 265 with HCV/HIV, 251 with
HCV alone, 227 with HIV alone
Mortality over a 3-year period was:
 17% in those HIV/HCV co-infected
 9% in those with HIV alone
 6% in those with HCV alone

In co-infected, mortality varied by race
 Whites 31%
 Blacks 15%
(Merriman et al., 2006)
HIV/HCV Co-infection (3)

Effects of HCV co-infection on HIV
progression unknown
 accelerated clinical progression of HIV-1
(Mathurin et al., 1998; Tong, El-Farra, Reikes & Co, 1995)
 impaired CD4-cell recovery and faster HIV
disease progression in HCV co-infected patients
despite their receiving ART (Grueb, 2000)
 no impact on CD4 count, viral load, HIV
progression or survival (Hayashi et al, 1991; Thomas et
al., 1996; Mayor, 2006; Merriman et al., 2006)
HIV/HBV Co-infection

Mortality Rates:

14.2/1000 in HIV/HBV co-infected
1.7/1000 in HIV monoinfected
0.8/1000 in HBV monoinfected


HBV Testing

Recommended for specific at-risk groups
 men who have sex with men
 injection drug users
 patients on dialysis
 people with HIV
 pregnant women
 families, household members and sexual
contacts of HBV-infected persons
HBV Testing- Serologic Markers (1)

Evaluation includes serologic testing for
viral markers
 HBsAg: hepatitis B surface antigen; indicates
acute or chronic HBV infection
 HBsAb: antibody to HBV surface antigen, a
marker of HBV immunity
 HBeAg: usually positive when HBV is present; a
marker of high infectivity
HBV Testing- Serologic Markers (2)

Evaluation includes serologic testing for
viral markers
 Anti-HBc: antibody to the hepatitis B core
antigen; indicates past infection, either acute or
chronic
 Anti-HBe: antibody to the hepatitis B e antigen.
In those recovered from acute or chronic HBV
infection, anti-HBe, anti-HBc and anti-HBs will
be present
HBV Testing

HBV DNA Tests
 Used in conjunction with serologic testing for
patients being considered for treatment and to
evaluate response to treatment
 An unamplified HBV DNA assay with detection
limits of 105 to 106 copies/mL is the diagnostic
criterion for chronic HBV

Liver biopsy or alanine aminotransferase
(ALT) are recommended to assess the
degree of necroinflammation
HBV Treatment (1)

Goals of treatment
 viral suppression
 remission of liver disease
HBV Treatment (2)

First line treatment options

interferons


IFN--2a and 2b
Pegylated IFN--2a and 2b
 nucleoside/nucleotide analogs
 lamivudine
 adefovir dipivoxil
 entecavir
 telbivudine
 tenofovir
HBV Treatment (3)


Emtricitabine is effective against both HBV
and HIV but not yet FDA approved for HBV
infection
Recent data indicate that entecavir has HIV
activity and should not be used as
monotherapy for HBV in HIV-infected
patients who are not taking other ARVs
HBV Treatment (4)

Indicators of adequate response to
treatment
 undetectable serum HBV DNA
 HBeAg loss or seroconversion
 improved liver histology on biopsy
HIV/HBV Co-infection Treatment (1)

If need to treat HIV in an HIV/HBV coinfected patient: NRTI backbone of an
antiretroviral regimen could be
 tenofovir + emtricitabine
 tenofovir + lamivudine
 Monotherapy of HBV with lamivudine,
emtricitabine, or tenofovir should be avoided if
possible because of risk of resistance
HIV/HBV Co-infection Treatment (2)

If need to treat HIV and HBV
 combination of tenofovir + lamivudine or
tenofovir + emtricitabine should be considered
as first-choice NRTI backbones
 additional options include entecavir only in
combination with one of the three nucleosides
with activity against both viruses
 use of lamivudine, emtricitabine, or tenofovir as
the only active anti-HBV agent should be
avoided because of risk of HIV resistance
HIV/HBV Co-infection Treatment (3)

Treatment of HBV and not HIV
 Pegylated interferon-alpha, one option, does not
lead to development of drug-resistant HIV or
HBV mutations
 Adefovir dipivoxil is active against HBV but not
against HIV at the 10 mg dose; however, a
theoretical risk for development of HIV mutants
exists, because it is related to tenofovir.
 use of emtricitabine, lamivudine, or tenofovir
without a full HAART regimen should be
avoided because of the rapid development of
drug-resistant HIV mutations
HIV/HBV Co-infection Treatment (4)

If there is a need to discontinue lamivudine,
tenofovir, or emtricitabine
 Monitor clinical course with frequent liver
function tests, and consider the use of adefovir
dipivoxil or entecavir to prevent flares,
especially in patients with marginal hepatic
reserve
HCV Testing

Routinely test all HIV-infected patients
 First use the enzyme immunoassay (EIA) test
for anti-HCV antibodies
 if EIA is positive, use an HCV RNA assay to
document viremia
Note: Patients co-infected with HCV/HIV may have
negative HCV antibody tests because of
immunosuppression
HCV RNA Assays (1)

Used to confirm results of less sensitive
HCV antibody assay
 qualitative and quantitative assays to detect
HCV RNA use target amplification (PCR, TMA) or
signal amplification (branched DNA) techniques
 HCV RNA can be used to predict and monitor
response to treatment
 results of different assays are not easily
compared, so use same assay to monitor
response to treatment
HCV RNA Assays (2)

HCV RNA assays can be used in those with
HIV to establish HCV infection within 2
weeks of infection

HCV RNA assays can detect HCV RNA in
most patients with chronic HCV
Liver biopsy

Recommended by most experts to stage
degree of hepatic necrosis, inflammation
and fibrosis

Used to determine need for HCV treatment

False negatives can occur in 10%-30% of
cases (due to small size of biopsy
specimens and heterogeneous
distribution of liver fibrosis)
HCV RNA Genotyping



6 known genotypes of HCV
Genotype 1 most common in the U.S .
Use of genotyping
 to determine the type and duration of treatment
 to assess likelihood of response to therapy

Patients with genotype 1 have much lower
rates of response to treatment than those
with genotype 2 or 3
ALT and AST


ALT- alanine aminotransferase
AST- aspartate aminotransferase
 Markers of hepatic cell damage
 Not sensitive or specific markers of disease
progression
 Can be useful in monitoring treatment effects
HCV Treatment Goals

Goals of treatment for chronic HCV
 Viral eradication (undetectable viral load)
 Prevent progression of liver disease

Best indicator of treatment is sustained
virologic response (SVR)
Sustained Virologic Response

Serum HCV RNA is undetectable based on a
qualitative HCV RNA assay with lower limit
of detection of 50 IU/mL or less at 24 weeks
after treatment ends
HCV Treatment (1)

Combination therapy with pegylated
interferon (PEG-IFN) alfa plus ribavirin is
most effective treatment for HCV in patients
with or without HIV; with this treatment:
 50% of HCV genotype 1 monoinfected patients
achieve HCV viral clearance
 HCV/HIV-coinfected genotype 1 patients have a
22%-29% SVR rate if treated for 48 weeks
 with other genotypes, there is a 55% SVR rate
HCV Treatment (2)

Ribavirin is teratogenic

Both men and women must use
contraception during and for 6 months after
treatment with ribavirin
HCV Treatment (3)

Those who are not candidates for treatment
for HCV include:
 those actively using alcohol
 those with untreated depression
 those with renal disease
 those with advanced cirrhosis
 pregnant women
(NIH, 2002)
HCV Treatment (4)

Although pregnant women and persons with
active alcohol use should not receive HCV
treatment, certain individuals with renal
disease, depression, injection drug use, and
lower degrees of hepatic fibrosis can be
considered for HCV treatment
Considerations in HCV Treatment (1)

Ribavirin should not be given with
didanosine; drug-drug interactions can
cause pancreatitis and lactic acidosis

Some NRTIs and all NNRTIs and PIs can be
hepatotoxic, so transaminase levels should
be monitored
(Panel on Clinical Practices for Treatment of HIV Infection, 2008)
Considerations in HCV Treatment (2)

Higher rates of anemia are associated with
zidovudine combined with ribavirin

Growth factors may be needed manage IFNassociated neutropenia and ribavirinassociated anemia
(Panel on Clinical Practices for Treatment of HIV Infection, 2008)
Considerations in HCV Treatment (3)

In HIV/HCV co-infected
 Decision when to initiate HCV treatment is case
by case
 Initiating HIV treatment first can increase CD4
counts, may improve response to HCV therapy
 Initiating HCV treatment first (in those with high
CD4 counts and low viral load) can simplify
treatment and improve ART tolerability
HCV Patient Education (1)

To avoid infecting others avoid sharing:








toothbrushes
dental appliances
razors
sex toys
tattoo equipment
injection equipment
personal care items that may have blood on
them
Educate and encourage use of safer sex
practices
HCV Patient Education (2)

Recommend alcohol abstinence before and
during antiviral therapy
 Alcohol is a cofactor in progression of liver
disease to cirrhosis and HCC
 Alcohol use during therapy adversely affects
response to treatment

Assess readiness and refer to alcohol
treatment if appropriate
HCV Patient Education (3)

Assess readiness and counsel regarding
drug treatment programs if using injection
drugs

If drug treatment is not an option, provide
risk reduction education
 cleansing of injection equipment
 provide patient with a source of clean, single-
use needles if possible
HCV Patient Education (4)

Instruct to avoid exposure to hepatotoxins,
including hepatotoxic medications (eg,
acetaminophen in large doses, fluconazole,
and isoniazid)

Instruct to consult a health care
professional before taking any new
medicines, including over-the-counter,
alternative or herbal products
HCV Patient Education (5)

Instruct to avoid exposure to environmental
toxins
 solvents
 paint thinners
 pesticides

If using toxic chemicals
 work in a well-ventilated area
 wear gloves
 wear a protective face mask
HCV Patient Education (6)

If patient is pregnant or considering
pregnancy, discuss ways to decrease the
infection risk for the baby
HCV Patient Education (7)
Recommended Vaccinations:

Anyone with HCV should be tested for
immunity to HAV and HBV; those not
immune should receive the vaccines

All persons with chronic liver disease
should be vaccinated annually against
influenza and should receive
pneumoccocal vaccine
HCV Patient Education (8)

Side effects of interferon (fatigue,
depression, confusion) can interfere with
appointment and medication adherence
 Provide support to maximize adherence
 Conduct ongoing assessments and treat and
refer as needed for depression
HCV Patient Education (9)

To reduce adverse effects instruct patients
to:
 increase fluid intake
 eat small, frequent, well-balanced meals
 exercise as tolerated
 get adequate sleep and rest
 avoid crowds to prevent infection
 take interferon injections before going to bed so
will sleep through some of the adverse effects
Key Points (1)
1. Hepatitis A is transmitted through contact
with infected fecal matter.
2. Hepatitis B and C are transmitted through
exposure to infected blood and body fluids.
3. Chronic HBV (5-10% of those infected) and
chronic HCV infection (50-80% of those
infected) can cause cirrhosis, HCC and liver
failure.
Key Points (2)
4. HBV Testing
i. serologic testing for viral markers
recommended for
 men who have sex with men
 injection drug users
 patients on dialysis
 people with HIV
 pregnant women
 families, household members and sexual
contacts of HBV-infected persons
Key Points (3)
4. HBV Testing (cont.)
ii. HBV DNA tests used for patients being
considered for treatment and to evaluate
response to treatment
iii. Liver biopsy and ALT to assess degree of
necroinflammation
Key Points (4)
5.
HBV Treatment
A. First line treatment options
1) Interferons
2) Nucleoside/nucleotide analogs
B. Indicators of adequate response
1) undetectable serum HBV DNA
2) HBeAg loss or seroconversion
3) improved liver histology on
biopsy
Key Points (5)
6. HCV Testing
i.
ii.
iii.
iv.
v.
Test all HIV+ patients
Use EIA for anti-HCV antibodies
If EIA positive, confirm with HCV RNA assay
to document viremia
HCV genotying to determine type/duration
of treatment
Liver biopsy to determine need for
treatment
Key Points (6)
7. HCV Treatment
i.
ii.
PEG-IFN alfa plus ribavirin
Educate patients and assess readiness for
treatment
i. avoid infecting others
ii. avoid alcohol and drugs
iii. avoid hepatotoxins
iv. receive HAV and HBV vaccines