HIV and Hepatitis Co-infection by Bj84Hy8l

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									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 <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 co-
    infected 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 [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 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 IFN-
    associated neutropenia and ribavirin-
    associated 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.     Test all HIV+ patients
    ii.    Use EIA for anti-HCV antibodies
    iii.   If EIA positive, confirm with HCV RNA assay
           to document viremia
    iv.    HCV genotying to determine type/duration
           of treatment
    v.     Liver biopsy to determine need for
           treatment
                  Key Points (6)
7. HCV Treatment
    i.    PEG-IFN alfa plus ribavirin

    ii.   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

								
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