Clinical Management of Hepatitis C Virus Infection in the HIV-Infected Patient

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Clinical Management of Hepatitis C Virus
Infection in the HIV-Infected Patient
Kathleen A. Clanon, MD
The International AIDS SocietyUSA
KA Clanon, MD. Presented at RWCA Clinical
Conference, June 2003.
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Starting Assertions

• HCV is a common comorbidity for HIV patients
  (approx 25-40 in U.S.).
• Liver disease is a significant and rising cause
  of death among HIV patients.
• Current treatment for HCV is poor, and we only
  use it when inaction is even more dangerous.
• HIV clinicians are struggling with how much of
  the care of HCV co-infected patients they can and
  should take on themselves.

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Prognosis in HIV/HCV Can We Ignore HCV?

• Retrospective study of 240 coinfected pts who
  died in 2000.
• Causes of death
• 33 End-stage liver disease
• 28 AIDS related
• At death
• 38 had CD4 gt200 cells/mm3
• 37 had undetectable HIV viral load

Dominique, S. et al, 42nd ICAAC, San Diego, 2002,
1719
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Prognosis in HIV/HCV Can We Wait for Better
Treatment?

• European Collaborative Study, 492 HIV/HCV pts.
• 50 severe liver fibrosis (F3 or F4) after 15 yrs
  HCV infection. 1
• The PANFIBROSIS Group, 4,852 pts with CLD, 180
  with HIV/HCV.
• Most rapid rate of progression to fibrosis of the
  8 top chronic liver diseases.
• 50 cirrhosis percentile at age 52.2
• 1. Martin-Carbonero, L et al. 10th CROI,
  Abstract 830, 2/03.
• 2. Poynard, T et al. J Hepatol 38(3)257-265.
  3/03.

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Goals for HCV Treatment

• Eradicate HCV (if HIV is stable and CD4gt200).
• Delay progression of liver disease and death (if
  CD4lt200).
• Make HAART safer, more tolerable by reducing
  liver toxicity.
• Reduce pain, offer hope, stave off transplant.

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Phase I Screening and Diagnosis

• Test every HIV-positive patient for anti-HCV EIA
  ab.1
• False-negative ab has been reported in HIV (3.4
  in one cohort).2 If high risk and neg HCV ab, but
  abnl ALT, check HCV PCR.
• If HCV pos., check PCR to confirm active
  infection (10-15 spontaneous clearance in
  monoinfected).

1. USPHS Guidelines for Preventing OI in PWHIV,
1999. 2. Boyle B and Vaamonde C. DDW, May 2002,
San Francisco, Abs 106665.
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Phase II Counseling and HCM

• Counseling Topics
• Prognosis of HCV/HIV co-infection and basics of
  treatment.
• Importance of avoiding EtOH (and hepatotoxic
  meds).
• How to prevent further transmission (sex, drugs,
  needle exchange).

NIH Consensus Statement 2002.
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Phase II Counseling and HCM

• Health Care Maintenance
• Alcohol and drug treatment referral.
• Referral to peer support resources.
• Hep A and B vaccines, for those not yet immune.
• Intensified monitoring of ALT/AST for those on
  HAART.

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Phase III Evaluation for IFN/RBV Rx of HCV

• Medical assessment
• HCV genotype (Type 1 most common in U.S., also
  most difficult to treat).
• ALT/AST, PT/PTT, alb, bili, CBC
• TSH and ANA
• AFP, ferritin
• Pregnancy test, urine tox?
• Liver biopsy to assess fibrosis and inflammation
  scores. (Neither ALT nor HCV PCR is predictive.)

www.va.gov/hepatitisc
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Phase III Evaluation for IFN/RBV Rx of HCV

• Medical factors Strong indications for Rx
• Pt has portal or bridging fibrosis and mod
  inflammation or necrosis on biopsy or
• Clinical signs of compensated cirrhosis and
• Persistently elevated ALT and detectable HCV RNA.
• High CD4 and patient not yet on HAART.

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Phase III Evaluation for IFN/RBV Rx of HCV

• Medical factors Contraindications
• Signs of decompensated cirrhosis
• (Varices, encephalopathy, ascites, etc.)
• HIV is unstable, recent O.I.s.
• Severe anemia, pltlt75K, or WBClt1.5k.
• Severe or uncontrolled depression.
• Pt is pregnant, breastfeeding, or may get someone
  else pregnant.

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Phase IV Supervising INF/RBV Rx

• Choice of therapy and duration
• Peginterferon alfa plus ribavirin has best
  efficacy, once a week injection.
• Duration
• 48 weeks for genotype 1 or 4.
• 24 weeks for other genotypes.

www.va.gov/hepatitisc
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Phase IV Supervising INF/RBV Rx

• Monitoring efficacy, signs of success
• Normalization of ALT
• Undetectable HCV RNA at
• 24 weeks (consider stopping if still detectable
  by then)
• End of Treatment (ETR)
• Sustained 6 months after Rx (SVR)

www.va.gov/hepatitisc
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Phase IV Supervising INF/RBV Rx

• Complications and monitoring
• Hemolytic anemia and leukopenia are rapid,
  profound in HIV.
• CBC with diff. at wk 1, then q 2 weeks initially.
  
• Low threshold for epo and/or G-CSF.
• Reduce RBV dose by 200 mg/d if Hgb drops gt4 gm.
• Depression very common, consider pre-treatment
  SSRI.
• Be alert for signs of lactic acidosis, no
  screening recommended as yet.
• Recheck TSH q 6 months.
• Pregnancy test q month during and for 6 months
  after Rx.

www.va.gov/hepatitisc
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HCV Websites

• For providers
• www.cdc.gov/ncidod/diseases/hepatitis
• www.hivandhepatitis.com
• www.va.gov/hepatitisc
• For clients/patients
• www.thebody.com
• www.hcvadvocate .org