HIV and Hepatitis C Coinfection

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HIV and Hepatitis C Co-infection

• Amy Kindrick, M.D., M.P.H.
• San Francisco AIDS Education and Training Center
• National HIV/AIDS Clinicians Consultation Center

February 21, 2003
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The Hepatitis C Virus
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Is There Only One Kind of Hepatitis?
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HCV Has Broad Global Prevalence
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HCV Infection Epidemiology

• 50 million infected worldwide
• 5 million in Europe
• 4 million in USA
• Contributes to 12,000 deaths/yr

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Hepatitis C Virus Infection

• U.S. Overall antibody prevalence 1.8
• 64 positive for HCV RNA
• Estimated 2.7 million persons chronically
  infected
• Parenteral transmission route
• Current risk of transfusion lt 1 in 1,000,000

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How Is HCV Transmitted?

• Infected blood
• Occupational percutaneous or mucosal exposure
• Est. 1.8 transmission rate after needle stick
• Needle sharing
• Transfusion (very rare since mid 1990s)
• Infected body fluids
• Amniotic fluid
• Perinatal transmission rate est. 3 - 5
• ? Genital secretions
• Inefficient sexual transmission

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HCV Diagnosis

• Enzyme immunoassays (EIA)
• Initial screening test for patients with liver
  disease
• False positives in low risk patients
• Occasional false negatives, esp. With HIV
• Recombinant immunoblot assays (RIBA)
• Confirmatory test if EIA positive in low risk pt
• HCV RNA by PCR or bDNA
• Confirmatory if RIBA is indeterminant

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Who Should Be Tested?

• Drug users
• Recipients of blood products or organ transplant
  before 1992
• HIV-infected individuals
• Children born to HCV-infected mothers
• Persons with occupational exposures
• Long-term partners of infected individuals

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Consider Testing For

• Persons with tattoos or body piercing
• Persons with multiple sexual partners

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Acute Hepatitis C Virus Infection

• Incubation period 2-26 weeks
• Acute infection may be asymptomatic
• Relatively long window period

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Acute Hepatitis C
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Hepatitis C Virus Infection Natural History

• Clinical course is variable
• Chronic infection in 70 85
• Cirrhosis in 10 20 of chronically infected
• Develops in 15 25 years
• Hepatocellular carcinoma
• 1 5 after 20 years
• 1 4 per year once cirrhosis is established

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Vaccinate, Vaccinate, Vaccinate
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Stigmata of Chronic Liver Disease
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Esophageal Varices
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Chronic HCV Infection With Cirrhosis
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Hepatocellular Carcinoma
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Hepatocellular Carcinoma
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Extrahepatic Manifestations of HCV

• Arthritis
• Glomerulonephritis
• Mixed cryoglobulinemia

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Mixed Cryoglobulinemia
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HCV/HIV Co-infectionGeneral Issues

• 150,000 300,000 prevalent cases in U.S.
• Average prevalence 35
• Varies geographically and by HIV risk behavior
• 80 90 in HIV IDUs
• gt 50 in incarcerated persons with HIV
• lt 10 in MSM
• Major transmission route is IDU
• Enhanced HCV vertical transmission
• 15-35 in co-infected vs 3-5 in HCV
  mono-infected
• ? Enhanced sexual HCV transmission

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Diagnosis of HCV in HIV-infected Patients

• Co-infection may reduce sensitivity of HCV
  antibody tests (EIA or RIBA)
• 9 19 Ab negative, RNA positive
• Measure HCV RNA if history or clinical symptoms
  are suggestive

George, et al. JAIDS 31154, 2002
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Impact of HIV on HCV

• HIV infection worsens HCV-related liver disease
• 2.9 fold increase in risk of progressive liver
  disease
• ALT levels higher
• Fibrosis more severe
• Time to fibrosis shorter
• Cirrhosis, liver failure, and HCC more common
• Liver-related death rates higher
• Vertical HCV transmission enhanced
• Impaired Th1 function in HIV infection may affect
  immune response to HCV

Graham, et al. CID 33562, 2001
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Impact of HCV on HIV

• Conflicting clinical results
• More rapid progression to AIDS or death for HCV
  genotype 1
• Increasing HIV RNA and decreasing CD4 more likely
  in co-infected pts
• May interfere with optimal HAART

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Treating Hepatitis C
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HCV Treatment Rationale

• Viral eradication
• Better HCV outcomes
• Decrease fibrosis
• Decrease rate of fatal hepatocellular carcinomas
• Increase T-cell responsiveness to HCV antigens
• Better HIV outcomes
• Reduce hepatic toxicity of ARVs

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HCV Treatment Options

• Interferon monotherapy
• Sustained response rates similar to HCV-infected
  alone
• Weak correlation with CD4 counts
• Interferon-ribavirin combination therapy
• Superior to monotherapy
• Co-infection trials ongoing
• Preliminary findings encouraging

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Combination Therapy Vs. Monotherapy

• Randomized placebo controlled trial of
• 110 co-infected pts
• Standard IFN plus ribavirin or placebo
• Combo superior to mono at 12 weeks
• HCV RNA undetectable in 23 vs 5 (P0.016)
• Discontinuation for toxicity similar (23 vs 18)

Kostman, et al. 1st IAS Conf., Buenos Aires 2001
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PEG vs Standard IFN RIBAVIC Trial

• Randomized open-label trial
• 416 co-infected pts
• CD4 gt 200
• Stable HIV RNA (on or off HAART)
• PegIFN/RBV vs standard IFN/RBV for 48 weeks
• Peg/RBV superior to standard/RBV
• 48 vs 27 response rates (P0.009)
• Adverse event profiles similar
• 28 vs 20

AIDS 2002 Barcelona, LbOr 16
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Interferon-Ribavirin Toxicity

• Flu-like symptoms
• Depression
• Leukopenia
• Anemia
• ? Reduced effectiveness of ARV therapy with
  ribavirin
• May inhibit intracellular AZT and d4T
  phosphorylation
• Not substantiated with clinical data

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Contraindications For HCV Treatment

• Absolute
• Hypersensitivity to IFN or RBV
• Autoimmune disease
• Decompensated liver disease
• Pregnancy
• Hemoglobinopathies
• Active OI

• Relative
• Severe psychiatric disorder
• Coronary artery disease
• Pancreatitis
• Uncontrolled diabetes
• Seizure disorder

Expert Perspectives III Strategies for the
Management of HIV/HCV Coinfection, 2002.
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What About OTC Medications?
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Complementary Therapies

• For liver disease
• Milk thistle (silymarin)
• Licorice root (glycyrrhizin)
• Toxicity possible with high doses
• gt100 mg glycyrrhizin/day OR
• gt3 grams licorice root/day for gt 6 weeks
• Ginseng
• For treatment-related symptoms
• Ginger

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HCV Future Treatment Options

• HCV-specific viral enzyme inhibitors
• Helicase
• Protease
• RNA polymerase
• Internal ribosomal entry site inhibitors
• Antisense nucleotides
• Vaccination

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Clinical Case

• 34 y/o HIV-infected man
• HIV in 1991
• H/O IDU and alcohol use
• Persistent transaminitis (ALT 160-280)
• Negative HBV and HCV serologies

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Clinical Case HIV Therapy

• Initial CD4 50, HIV RNA 100,000
• 6/98 d4T, 3TC, ADF (renal toxicity)
• 8/98 ABC, 3TC, NLF, EFV
• 11/98 NLF stopped for rash
• 12/98 transaminitis
• 3/99 all ARVs stopped (despite VLgt1 mil)
• 6/99 d4T, 3TC, ABC, NLF (jaundice)

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HCV Clinical Evaluation

• HCV antibody
• HCV viral load
• HCV genotype
• Liver function tests
• Liver biopsy
• Gold standard for assessing disease status
• ALT and AST do not predict liver histology
• HCV RNA does not predict liver histology or
  outcomes

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Clinical Case Diagnosis

• Liver biopsy
• Fibrous expansion of portal areas, portal
  inflammation, piecemeal necrosis, activity in
  gt2/3 of lobules

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Clinical Case Management Challenge

• Hold ARVs until LFTs normalize, then restart with
  different agents
• Stop ARVs and treat HCV
• Continue ARVs and treat HCV

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Co-Infection Summary

• Natural course of chronic HCV accelerated by
  concurrent HIV infection
• Counsel alcohol and hepatotoxin avoidance
• Vaccinate!!
• Consider treatment for coinfected patients with
  stable HIV and good clinical, functional status
• New treatment options for chronic HCV should be
  urgently explored

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Consultation Services for Clinicians Caring for
Patients with HIV/AIDS

• Local expert clinicians
• Regional and local AIDS Education and Training
  Centers
• National HIV Telephone Consultation Service
  (Warmline)
• [phone]
• National Clinicians Post-Exposure Prophylaxis
  Hotline (PEPline)
• (888) HIV-4911

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National HIV/AIDS Clinicians Consultation Center

• A Joint Program of UCSF
• and San Francisco General Hospital
• Supported by HRSA and CDC
• http//www.ucsf.edu/hivcntr
• PEPLine [phone]
• Warmline [phone]