COMMENTARY

HIV and Hepatitis C Co-infection: Guideline and Commentary

Douglas G. Fish, MD

Disclosures

January 05, 2011

In This Article

Deciding Whether to Treat HCV in HIV-Infected Patients

Recommendations. When performing a medical evaluation for anti-HCV treatment in HIV/HCV co-infected patients, clinicians should consult with a hepatologist or other provider with experience in treating HCV. (AIII)

Clinicians should individualize the decision to treat HCV based on the following factors (AIII):

  • Contraindications and relative contraindications to therapy (see Table 2)

  • Whether the patient has acute HCV

  • Likelihood of response to treatment of chronic HCV (see Table 3)

  • Likelihood of progression of fibrosis in the absence of treatment (see Table 3)

  • Immune status

  • Extent of liver damage

  • HCV and HIV viral loads

  • Risk for adverse effects of treatment

  • Motivation for treatment and barriers to adherence to therapy

  • CD4 count

Patients with acute HCV who remain positive for HCV RNA 12 weeks after infection should be treated with combination pegylated interferon and ribavirin. (BIII)

Consideration of the factors used to guide the decision to treat HCV infection, including contraindications for HCV treatment, likelihood of progression of fibrosis without treatment, and the medical evaluation for potential anti-HCV treatment, should be in consultation with a hepatologist or other clinician with experience in HCV treatment.

Contraindications to Anti-HCV Therapy

Recommendations. Clinicians should not prescribe anti-HCV treatment for HIV/HCV co-infected patients with any of the absolute contraindications listed in Table 2.

Clinicians should address any of the relative contraindications listed in Table 2 before prescribing anti-HCV therapy.

Among the considerations for anti-HCV therapy, assessment for contraindications to therapy is essential. Table 2 lists contraindications that would prevent initiation of anti-HCV treatment in HIV/HCV co-infected patients, as well as relative contraindications that, once addressed, would not affect the decision to treat.

Table 2. Contraindications for HCV Treatment in Patients with HIV/HCV Co-infection

Contraindications

  • Allergy to interferon/ribavirin

  • Patients on dialysis or with creatinine clearance <50 mL/min

  • Hemoglobinopathies (eg, thalassemia major and sickle cell anemia)

  • Autoimmune hepatitis

  • Uncontrolled thyroid disease

  • Pregnant/nursing women, women unable to practice contraception, or men with pregnant partners

  • Current suicidal behavior or uncontrolled severe psychiatric illness

  • Severe cardiac disease (eg, unstable angina, unstable arrhythmias)

  • Decompensated cirrhosis

  • Sarcoidosis or unexplained pulmonary infiltrates

  • Heart, lung, and kidney transplants

  • Neonates and infants

  • Patients receiving didanosine a

Relative Contraindications

  • Hb <10 g/dL b

  • White blood cells <1500 cells/mm3b

  • Platelets <90,000/mm3

  • CD4 <100 cells/mm3

  • Uncontrolled diabetes mellitus

  • Other autoimmune disorders (eg, lupus, rheumatoid arthritis)

  • Ongoing heavy alcohol use c

  • Active substance use if adherence to treatment is a concern d

  • Untreated mental health disorder e

  • Previous suicidal behavior e

Hb, hemoglobin.
See package inserts for pegylated interferon and ribavirin for full details.
a The combination of ribavirin and didanosine has demonstrated an increased risk for pancreatitis, lactic acidosis, hepatic decompensation, and death in patients with cirrhosis. Therefore, the combination is contraindicated.
b These hematologic deficiencies can be corrected with hematopoietic growth factors. For example, patients receiving zidovudine may develop correctable granulocytopenia or severe anemia. Once corrected, such patients may be eligible for treatment.
c Patients with alcohol dependence should be referred for alcohol-dependency treatment before initiation of anti-HCV therapy. For more information regarding alcohol dependence in HIV-infected patients, see Clinical Management of Alcohol Use and Abuse in HIV-Infected Patients .
d Active substance use is not a contraindication to anti-HCV treatment unless the clinician determines that it could interfere with adherence. Such a determination may be established on a case-by-case basis with the patient’s adherence to HIV treatment as a guide.
e Patients with a history of mental health disorders may safely complete a course of treatment if the disorder is in remission and there is sufficient interdisciplinary support.[44] Treatment of these individuals should be undertaken in consultation with a psychiatrist.

Untreated Mental Health Disorders

Recommendations. When untreated mental health disorders are identified in HIV/HCV co-infected patients, clinicians should make appropriate referrals for mental health treatment before initiating anti-HCV therapy. (AII)

For patients with a suspected mental health disorder that is untreated, clinicians should refer the patient for mental health evaluation and treatment before consideration of anti-HCV therapy. See Section 5: Evaluation and Initial Management of Confirmed Hepatitis C Infection.

Heavy Alcohol and Substance Use

Recommendations. Clinicians should screen patients for alcohol and substance use dependence before initiating anti-HCV treatment. (AII)

When untreated alcohol dependence is identified in HIV/HCV co-infected patients, clinicians should make appropriate referrals for substance-dependency treatment before initiating anti-HCV therapy. (AII)

One study found an inverse correlation between rates of response to interferon treatment and levels of alcohol intake during therapy.[45] Furthermore, there are reports of acute alcoholic hepatitis in several individuals consuming alcohol during interferon treatment.[46] Heavy drinkers are unlikely to achieve SVR. (See Section 5: Evaluation and Initial Management of Confirmed Hepatitis C Infection.)

Key Point

Unlike heavy alcohol use, active substance use does not induce hepatotoxicity when combined with anti-HCV treatment. Active substance use, including injection drug use, is not a contraindication to anti-HCV treatment unless the clinician determines that it could interfere with adherence to treatment. Such a determination may be established on a case-by-case basis, using the patient’s adherence to HIV treatment as a guide.


Assessment for Treatment of Acute HCV Infection. Treatment of acute infection is an important consideration for HIV-infected patients. The greater risk for chronic infection among HIV-infected patients co-infected with HCV, and the excellent treatment responses in mono-infected patients with acute HCV,[12] argue for consideration of anti-HCV therapy in HIV-infected patients who develop acute HCV. Good treatment responses have been seen even in patients infected with HCV genotypes 1 and 4. In general, if patients acutely infected with HCV are still positive for HCV RNA by 12 weeks after infection, treatment should be considered.

Assessment of Patients at Greatest Risk for Cirrhosis. Patients at greatest risk for progression to cirrhosis should be considered candidates for anti-HCV therapy (see Table 3). Patients who are most likely to progress to cirrhosis include those with persistently elevated serum ALT and those with a liver biopsy that reveals greater than stage 2 fibrosis (ie, patients with at least periportal fibrosis on biopsy). However, because HIV itself is a risk factor for increased progression of HCV, serious consideration should be given to treatment of patients with minimal fibrosis or portal fibrosis (ie, an Ishak score of F1). Table 4 outlines National Institutes of Health recommendations[13] for HIV/HCV co-infected patients with minimal fibrosis or portal fibrosis.

Table 3. HCV Treatment Considerations For Patients With HIV/HVC Co-infection

Factors associated with progression to cirrhosis without treatment
  • Male sex

  • Alcohol use >30 g/day for men and >20 g/day for women

  • Infected at ≥40 years of age

  • Portal or bridging fibrosis or at least moderate inflammation or necrosis

  • HIV/HCV/HBV tri-infection

  • Elevated serum AST and ALT levels

Factors associated with favorable response to therapy
  • HCV genotype 2 or 3 and, to a lesser extent, genotype 4 (rather than 1a or 1b)

  • Low level of serum HCV RNA before treatment (<800,000 IU/mL)

  • Age <40 years

  • Duration of disease <5 years

  • Absence of cirrhosis or only minimal histologic evidence of fibrosis

  • Low concentrations of iron in liver tissue before treatment

  • Rapid clearance of HCV RNA

  • Abstinence from alcohol or avoidance of heavy alcohol use

  • Absence of hepatosteatosis

  • Insulin responsiveness

HCV-induced extrahepatic disorders that indicate need for therapy
  • Cryoglobulin vasculitis

  • Glomerulonephritis

Table 4. Current Treatment Guidelines for Patients With HIV/HVC Co-infection*

Patient Characteristics

Treatment Recommendations

Minimal fibrosis on liver biopsy
  • Treat with pegylated interferon plus ribavirin if there are no contraindications

or

  • Observation, serial ALT and AST levels every 6 months, liver biopsy every 3 to 5 years

Persistent HCV viremia and liver biopsy showing portal or bridging fibrosis, compensated cirrhosis, or moderate inflammation or necrosis Treat with pegylated interferon plus ribavirin if there are no contraindications (assess risks and benefits on a case-by-case basis)
Decompensated cirrhosis Consider evaluation for liver transplant
* Decisions to treat should be individualized.


ALT Levels in HIV/HCV Co-infected Patients. Patient motivation, age, duration of infection, degree of fibrosis, viral genotype, and HCV RNA may be considered when deciding whether to treat HIV-infected patients with normal ALT levels.[47] A higher prevalence of liver fibrosis has been found in HIV/HCV co-infected patients with a normal ALT, and in 2 studies, cirrhosis was found on liver biopsy in 12% to 14% of patients with a normal ALT.[48,49] According to the 2007 updated recommendations from the HCV-HIV International Panel, co-infected patients with normal ALT levels should be considered for treatment if there are no contraindications.[50] Some experts consider increased ALT levels over baseline to be abnormal for HCV-infected patients, even when the increased levels are within the upper limit of normal.[51]

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