1. COMPLICATIONS: VIRAL INFECTIONS (HCV & HIV) Nairobi, Kenya June 25, 2013

2. OBJECTIVES Explore the history of blood-borne viral infections Discuss two viral infections seen in hemophilia patients: HCV and HIV Distinguish types and subtypes of each virus Examine exposure risk with each virus List ways to minimize exposure Share treatment approaches for infected patients

3. HISTORY OF BLOOD-BORNE VIRUSES Transmission of blood-borne diseases occurs after exposure to blood-derived treatment therapies (factor concentrates developed in the mid-1960s): Hepatitis B: HBV Hepatitis non-A, non-B, later called “C” HIV (late 1970s to mid-1980s) Mannucci PM, et al. J Clin Pathol. 1975;28(8):620-624. Schramm W, et al. Blut. 1989;59(4):390-392.

4. HISTORY OF BLOOD-BORNE VIRUSES (CONT’D) In earlier years of treatment, hepatitis B and non-A, non-B (now called hepatitis C) were considered “acceptable risks” for patients receiving plasma-derived factor concentrates Hepatitis B usually resulted in immunity after exposure (90% of cases) Non-A, non-B considered “non-problematic” due to long latency period with few symptoms noted until late in disease process We now know about 85% of patients infected with hepatitis C develop chronic hepatitis Seeff LB. Am J Med. Dec. 1999;107[6B]:10S-15S.

5. HEPATITIS Definition “Inflammation of the liver, usually producing swelling and tenderness and sometimes permanent damage to the liver.” - American Liver Foundation G H. Types of hepatitis A B C D E

6. HEPATITIS: SIGNS & SYMPTOMS Fatigue, weakness Mild fever Nausea Vomiting and diarrhea Poor appetite Abdominal pain Muscle and joint aches Weight loss Changes in color of urine and stool Jaundice

7. HEPATITIS B VIRUS: HBV Lipid-enveloped DNA virus Replicates within liver cells Transmitted by exchange of bodily fluids 90% recover with immunity; 10% develop chronic HBV of which 20-30% progress to cirrhosis Sensitive to heat and solvent/detergent 1981: Hep B vaccine (plasma- derived) 1987: Hep B vaccine (recombinant) licensed Electron micrograph of Hepatitis B Virions (courtesy of the CDC)

8. HEPATITIS C VIRUS: HCV Lipid-enveloped RNA virus Replicates within infected liver cells Transmitted by the exchange of bodily fluids 85% or more with acute HCV infection progress to chronic hepatitis * Sensitive to heat and solvent/detergent No vaccine available * Seeff LB. Am J Med. Dec. 1999;107[6B]:10S-15S.

9. HEPATITIS C: OVERVIEW 150,000 new cases per year ~4 million Americans with chronic HCV 8,000-10,000 deaths annually Leading cause of liver transplantation 20% of cases develop cirrhosis ~8% develop hepatocellular carcinoma (HCC) Progression to severe disease may take decades

10. HEPATITIS C: ROUTES OF TRANSMISSION IV drug use Transfusions/blood products Sexually (low frequency) Mother to child at birth (rarely)

11. HEPATITIS C: TESTING Detection of virus Antibodies against HCV (EIA-3, RIBA) Presence of virus (RT-PCR, qualitative) # of copies of virus (RT-PCR, quantitative) Liver function tests ALT (alanine aminotransferase) AST (aspartate aminotransferase) Alkaline phosphatase Albumin PT (prothrombin time) Bilirubin

12. HEPATITIS C: GENOTYPES I a, b, c II a, b III a, b IV V VI McHutchison et al. N Engl J Med. 1998;339:1485.

13. HEPATITIS C IN HEMOPHILIA PATIENTS >80% of people with hemophilia in US are HCV positive Significant cause of morbidity and mortality 30-50% co-infected with HIV Co-infection accelerates progression to end-stage liver disease (ESLD) Contreras Jorge MS. Ann of Hepatology. 2006; 5(Suppl 1): S56-S57. Fried MW. Am J Med. 1999; 107: 85S-89S.

14. HEPATITIS C: THERAPY Pegylated interferon (Peg-IFN) Non-pegylated interferon a-2b (rarely used anymore) Used in combination with ribavirin (800-1200 mg daily) 24-48 weeks of therapy Intermediate goals Normalization of liver function Reduction of viral load Improvement in liver cells Long-term goal Sustained viral response (SVR): negative viral load six months after therapy complete

15. HEPATITIS C: FACTORS PREDICTIVE OF FAVORABLE RESPONSE TO IFN + RBV Genotype 2 or 3 HCV RNA < 2 x 10 6 copies/ml Age < 40 years Minimal fibrosis stage Female sex Poynard, et al. Lancet. 1998; 352:1426.

16. HEPATITIS C: COMMON SIDE EFFECTS OF IFN Flu-like symptoms Mood changes Nausea, diarrhea Abdominal pain Decreased WBCs (leukopenia), platelet count (thrombocytopenia) & RBCs (anemia) Teratogenic Proteinuria

17. HEPATITIS C: SERIOUS ADVERSE EVENTS WITH IFN Seizures Suicide attempts Autoimmune disease: SLE, thyroiditis Hepatic decompensation Acute renal failure Sudden death

18. HUMAN IMMUNODEFICIENCY VIRUS (HIV)

19. HIV AND AIDS H = Infects only Humans I = Immunodeficiency: weakening of the immune system → increased risk of infection V = Virus that attacks the body A= Acquired, not inherited I = Weakens the Immune system D = Creates a Deficiency of CD4+ cells S = Syndrome

20. HIV AND AIDS (CONT’D) When the immune system becomes weakened by HIV, the illness progresses to AIDS Some blood tests, symptoms or certain infections indicate progression of HIV to AIDS

21. HIV-1 AND HIV-2 HIV-1 and HIV-2 are –Transmitted through the same routes –Associated with similar opportunistic infections HIV-1 is more common worldwide HIV-2 is found in West Africa, Mozambique, and Angola

22. HIV: TRANSMISSION Direct contact with infected blood Sexual contact: oral, anal, or vaginal Direct contact with semen or vaginal and cervical secretions HIV-infected mothers to infants during pregnancy, delivery, or breastfeeding

23. HIV: PREVENTION OF TRANSMISSION Public health strategies to prevent HIV transmission Screen all blood and blood products Follow universal precautions Educate in safer sex practices Identify and treat STIs/other infections Provide referral for treatment of drug dependence Apply the comprehensive PPTCT approach to prevent vertical transmission of HIV

24. HIV: NATURAL HISTORY OF INFECTION Immune suppression HIV attacks white blood cells, called CD4 cells, that protect body from illness Over time, the body’s ability to fight common infections is lost Opportunistic infections occur Progression of HIV disease is measured by: CD4+ count −Degree of immune suppression −Lower CD4+ count means decreasing immunity Viral load –Amount of virus in the blood –Higher viral load means more immune suppression

25. HIV IN HEMOPHILIA 1980 to early 1990 many PWH died due to HIV, HBV, and HCV infections This risk has decreased dramatically and has been almost eliminated worldwide (blood banking and testing) Recombinant factor has reduced infections May be new viruses so must always test and PWH should be managed in HTCs

26. MANAGEMENT OF HIV IN PWH We use information obtained from the non-PWH population All PWH who use plasma-derived products that have not been virally inactivated i.e., FFP and cryoprecipitate, need to be tested for HIV & hepatitis B and C every 6-12 months Diagnosis, monitoring, and treatment of HIV need to be the same as the non-PWH population All current drugs used to treat HIV can be used in PWH Ref: Guidelines for the management of haemophilia, WFH working group, A Srivastava, J Mahlangu et el et el haemophilia 2012 P 62

27. PRINCIPLES OF MANAGEMENT OF BACTERIAL INFECTION IN HEMOPHILIA Risks of infection are more possible in PWH with venous catheter or port access and surgical procedures. Aspiration of joints needs to be avoided unless done early with strict aseptic technique and factor coverage Bleeding will delay healing and make the infection worse The infection must be treated with adequate antibiotics

28. SUMMARY Patients treated with blood products can be exposed to blood-borne pathogens PWH historically have been affected by blood-borne viruses HCV and HIV are susceptible to viral inactivation steps used to produce factor concentrates Improvements in blood donor screening and viral safety measures to produce clotting factors have greatly reduced blood-borne infections Treatments are available for those affected by HCV and HIV Education about viral infections continues to be a key role for hemophilia nurses

29. REFERENCES Slides HIV: The global and Indian scenario Dr. Kanupriya Chaturvedi Dr. S.K Chaturvedi Guidelines for the management of hemophilia, 2 nd edition Prepared by the Treatment Guidelines Working Group, on behalf of the WFH

30. ADDITIONAL WFH RESOURCES The Tragic History of AIDS in the Hemophilia Population, 1982–1984 New Approaches to the Management Of Hepatitis C In Hemophilia HIV and HCV Co-Infection in Hemophilia HCV-Related Liver Cancer in People with Hemophilia Conception in HIV-Discordant Couples Visit the Publications Library at www.wfh.org/publications for free copies www.wfh.org/publications