HIV and Hepatitis Co-infection

1
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

2
Objectives (1)

• 1. Describe transmission, signs and symptoms of
  Hepatitis A.
• 2. Describe transmission, signs and symptoms,
  testing, and treatment of Hepatitis B.

3
Objectives (2)

• 3. Describe transmission, signs and symptoms,
  testing, and treatment of Hepatitis C.
• 4. Discuss education of HCV infected patient.

4
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.

5
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

6
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

7
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

8
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

9
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

10
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

11
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.

12
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

13
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

14
Hepatitis C Virus (HCV) (3)

• 80 of those infected are asymptomatic
• 50-80 of immunocompetent people who become
  infected become chronically infected

15
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.

16
Sources of Infection with HCV (1) (CDC, 2006)
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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 populations frequency of sexual
  behaviors, plus prevalence of HCV, explains the
  high proportion (15) of HCV transmitted through
  sexual exposure

18
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

19
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

20
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

21
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)

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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)

23
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

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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

25
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

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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

27
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

28
HBV Treatment (1)

• Goals of treatment
• viral suppression
• remission of liver disease

29
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

30
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

31
HBV Treatment (4)

• Indicators of adequate response to treatment
• undetectable serum HBV DNA
• HBeAg loss or seroconversion
• improved liver histology on biopsy

32
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

33
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

34
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

35
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

36
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

37
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

38
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

39
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)

40
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

41
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

42
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)

43
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

44
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

45
HCV Treatment (2)

• Ribavirin is teratogenic
• Both men and women must use contraception during
  and for 6 months after treatment with ribavirin

46
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)

47
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

48
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)

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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)

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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

51
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

52
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

53
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

54
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

55
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

56
HCV Patient Education (6)

• If patient is pregnant or considering pregnancy,
  discuss ways to decrease the infection risk for
  the baby

57
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

58
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

59
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

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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.

61
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

62
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

63
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

64
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
  treatment
• Liver biopsy to determine need for treatment

65
Key Points (6)

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