1. Prepared by the AETC National Coordinating Resource Center based on recommendations from the CDC, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Hepatitis C Virus Disease Slide Set

2. 2 July 2013www.aidsetc.org These slides were developed using recommendations published in July 2013. The intended audience is clinicians involved in the care of patients with HIV. Certain sections have been updated to reflect changes in the published guidelines. Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. – AETC National Coordinating Resource Center http://www.aidsetc.org About This Presentation

3. 3 July 2013www.aidsetc.org  Epidemiology  Clinical Manifestations  Diagnosis  Preventing Exposure  Preventing Disease  Treatment  Preventing Recurrence  Considerations in Pregnancy Hepatitis C Virus

4. 4 July 2013www.aidsetc.org  HCV disease is a leading non-AIDS cause of death in HIV-infected persons  20-30% of HIV-infected U.S. patients have HCV coinfection  HCV is a single-stranded RNA virus  7 genotypes  Genotype 1: ~75% of HCV infections in United States; ~90% of HCV infections in U.S. blacks HCV Disease: Epidemiology

5. 5 July 2013  Transmission: percutaneous exposure, sexual exposure, perinatal, contaminated blood products or medical equipment  Percutaneous transmission:  HCV is 10 times more infectious than HIV through percutaneous blood exposures  Injection drug use is most common risk in the U.S. (via syringes or injection paraphernalia)  HCV can survive for weeks in syringes  Other risks: intranasal cocaine use, tattoo placement HCV Disease: Epidemiology (2) www.aidsetc.org

6. 6 July 2013www.aidsetc.org  Sexual transmission  HIV appears to increase risk of sexual transmission of HCV  In HIV-infected MSM, multiple outbreaks of acute HCV  Risk factors: unprotected receptive anal sex, sex toys, recreational drug use, concurrent STD  In HIV-uninfected MSM, HCV transmission inefficient  Heterosexual transmission uncommon; increased risk if partner is HIV/HCV coinfected HCV Disease: Epidemiology (3)

7. 7 July 2013www.aidsetc.org  Perinatal transmission  HIV appears to increase transmission risk  HCV incidence:  1-3% if HCV-infected mothers had detectable plasma HCV  4-7% if mothers had detectable plasma HCV RNA  10-20% if mothers had HIV/HCV coinfection HCV Disease: Epidemiology (4)

8. 8 July 2013www.aidsetc.org  HIV infection speeds progression of HCV to cirrhosis, especially if CD4 count is <200 cells/µL  HIV speeds progression from cirrhosis to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) HCV Disease: Epidemiology (5)

9. 9 July 2013www.aidsetc.org  Acute hepatitis C:  Usually asymptomatic or mildly symptomatic; usually not recognized  <20% have symptoms of acute hepatitis (eg, fever, right upper quadrant pain, nausea, vomiting, anorexia, jaundice)  Liver transaminases may be elevated  Recognizing possible acute HCV is important, given greater efficacy of treatment in early HCV HCV Disease: Clinical Manifestations

10. 10 July 2013www.aidsetc.org  Chronic hepatitis C:  Often asymptomatic  Fatigue is common  With progression, stigmata of portal hypertension (eg, spider angiomata, temporal wasting, splenomegaly, caput medusa, ascites, jaundice, pruritus, encephalopathy)  May see skin abnormalities (leukocytoclastic vasculitis, porphyria cutanea tarda), renal disease HCV Disease: Clinical Manifestations (2)

11. 11 July 2013www.aidsetc.org  Screen all HIV-infected patients for HCV at entry into care: sensitive immunoassay  For at-risk HCV uninfected, retest annually or as indicated by risk exposure  To confirm infection: HCV RNA by sensitive quantitative assay  HCV RNA does not correlate with HCV disease; should not be monitored serially unless on HCV treatment  HCV RNA correlated with likelihood of response to HCV treatment HCV Disease: Diagnosis

12. 12 July 2013www.aidsetc.org  False-negative HCV antibody results are possible in HIV- infected persons with advanced immunosuppression (<1%)  Negative HCV antibody result can occur during acute infection  Window period before seroconversion is 2-12 weeks  Test for HCV RNA if risk of HCV, high ALT, but negative or indeterminate serologic test HCV Disease: Diagnosis (2)

13. 13 July 2013  Encourage injection drug users to enter substance abuse treatment program  Advise IDUs not to share needles or drug preparation equipment if unable to stop using  Needle exchange may facilitate access to sterile equipment  Inform patients of risks associated with nonsterile body piercing, tattooing  Encourage safer sex, especially condom use, to reduce sexual transmission of HCV HCV Disease: Preventing Exposure www.aidsetc.org

14. 14 July 2013www.aidsetc.org  No vaccine or recommended postexposure prophylaxis  After acute HCV, treatment within 6-12 months may prevent chronic infection; high rates of HCV clearance  Acutely infected patients should be offered treatment, unless contraindications  Peginterferon (PegIFN) +/– ribavirin (RBV)  Some experts recommend observation for ~3-6 months to see if HCV will clear spontaneously HCV Disease: Preventing Disease

15. 15 July 2013www.aidsetc.org  Prevent liver damage:  Avoid alcohol consumption  Avoid hepatotoxins; limit acetaminophen intake (<2 g/day)  Avoid iron supplementation unless iron deficiency  Vaccinate against HAV, HBV if nonimmune  If cirrhosis, consult with specialist  Serial screening for HCC:  Optimal strategy unknown; some recommend ultrasound every 6-12 months  AFP has poor specificity and sensitivity; should not be used as the only screening method HCV Disease: Preventing Disease (2)

16. 16 July 2013www.aidsetc.org  Liver transplant is not absolutely contraindicated in HIV/HCV coinfection  May refer coinfected patients with well-controlled HIV and liver decompensation or early HCC  ART associated with reduced risk of liver disease progression  Treat with ART in accordance with usual ART guidelines  Dosage adjustment of some ARVs may be needed for patients with decompensated cirrhosis HCV Disease: Preventing Disease (3)

17. 17 July 2013www.aidsetc.org  Goals of treatment, therapy regimens, and monitoring parameters generally are the same for HIV/HCV- coinfected patients as for HCV monoinfected  HCV treatment is evolving rapidly and a number of new drugs are now available, with more expected within the next few years  See most recent HCV treatment guidelines (http://www.hcvguidelines.org) for current recommendations HCV Disease: Treatment

18. 18 July 2013www.aidsetc.org  No protective immunity after infection; reinfection possible if new exposure to HCV (eg, via injection drug use or unprotected sex)  Patients who achieve SVR should be counseled to avoid reinfection  Methods that prevent sexual transmission of HIV should prevent sexual transmission of HCV HCV Disease: Preventing Recurrence

19. 19 July 2013www.aidsetc.org  All HIV-infected pregnant women should be tested for HCV  Evaluation, including liver biopsy, can be delayed ≥3 months after delivery (pregnancy-related changes in HCV activity should resolve)  Hepatitis A and hepatitis B vaccination can be given; should be given if not immune HCV Disease: Considerations in Pregnancy

20. 20 July 2013www.aidsetc.org  HCV treatment with PegIFN and ribavirin is contraindicated during pregnancy  IFN: has antigrowth and antiproliferative effects; is abortifacient in monkeys  Ribavirin: FDA category X; teratogenic at low dosages in many animal species  Both women and men must be counseled about risks and need for consistent and effective contraception during ribavirin therapy and for 6 months after completion of therapy  BOC, TPV: pregnancy category B, but must be used with IFN and ribavirin, which are contraindicated HCV Disease: Considerations in Pregnancy (2)

21. 21 July 2013www.aidsetc.org  Perinatal HCV transmission: higher risk for HIV- coinfected women  Limited data on efficacy of medical or surgical preventive measures  Cesarean delivery does not decrease risk of perinatal HCV transmission, and may increase risk of maternal morbidity in HIV-infected women  Cesarean delivery in HIV/HCV-coinfected women can be considered based on HIV-related indications; data insufficient to support routine use for prevention of HCV transmission HCV Disease: Considerations in Pregnancy (3)

22. 22 July 2013www.aidsetc.org  http://www.aidsetc.org  http://aidsinfo.nih.gov Websites to Access the Guidelines

23. 23 July 2013www.aidsetc.org  This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in July 2013.  See the AETC NRC website for the most current version of this presentation: http://www.aidsetc.org About This Slide Set