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HIV and Hepatitis Co-infection


HBsAg: hepatitis B surface antigen; indicates acute or chronic HBV infection ... Recent data indicate that entecavir (Baraclude) has HIV activity and should not ... – PowerPoint PPT presentation

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Title: HIV and Hepatitis Co-infection

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
  • June 2008

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 lt2 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,
  • 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

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
  • Risk of HCV transmission through sexual exposure
    is low
  • However, general populations 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

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
    co-infected is related to HIV viral load and CD4

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
  • 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
  • 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
  • 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

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 Epivir
  • adefovir dipivoxil Hepsera
  • entecavir Baraclude)
  • telbivudine Tyzeka

HBV Treatment (3)
  • Tenofovir (Viread) and emtricitabine (Emtriva)
    are ARVs effective against both HBV and HIV but
    not FDA approved for HBV infection
  • Recent data indicate that entecavir (Baraclude)
    has HIV activity and should not be used as
    monotherapy for HBV in HIV-infected pts. 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 co-infected
    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
  • 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

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

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
  • 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
  • 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- alanine aminotransferase
  • AST- aspartate aminotransferase
  • Markers of hepatic cell damage
  • Not sensitive or specific markers of disease
  • 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

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
  • (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
    IFN-associated neutropenia and ribavirin-associate
    d 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
  • 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
  • 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
  • All persons with chronic liver disease should be
    vaccinated annually against influenza and should
  • 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

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
  • 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
  • Liver biopsy to determine need for treatment

Key Points (6)
  • 7. HCV Treatment
  • PEG-IFN alfa plus ribavirin
  • Educate patients and assess readiness for
  • avoid infecting others
  • avoid alcohol and drugs
  • avoid hepatotoxins
  • receive HAV and HBV vaccines