Download HIV - MULTIWEBCAST

COMPLICATIONS: VIRAL
INFECTIONS (HCV & HIV)
Nairobi, Kenya
June 25, 2013
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
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.
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.
HEPATITIS
Definition
“Inflammation of the liver, usually producing swelling and
tenderness and sometimes permanent damage to the liver.”
- American Liver Foundation
Types of hepatitis
• G
• A
• H
• B
• .
• C
• .
• D
• E
HEPATITIS: SIGNS & SYMPTOMS
• Fatigue, weakness
• Abdominal pain
• Mild fever
• Muscle and joint aches
• Nausea
• Weight loss
• Vomiting and diarrhea
• Changes in color of urine
and stool
• Poor appetite
• Jaundice
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 (plasmaderived)
• 1987: Hep B vaccine
(recombinant) licensed
Electron micrograph of Hepatitis B
Virions (courtesy of the CDC)
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.
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
HEPATITIS C: ROUTES OF TRANSMISSION
• IV drug use
• Transfusions/blood products
• Sexually (low frequency)
• Mother to child at birth (rarely)
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
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.
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.
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
HEPATITIS C: FACTORS PREDICTIVE OF FAVORABLE
RESPONSE TO IFN + RBV
•
•
•
•
•
Genotype 2 or 3
HCV RNA < 2 x 106 copies/ml
Age < 40 years
Minimal fibrosis stage
Female sex
Poynard, et al. Lancet. 1998; 352:1426.
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
HEPATITIS C: SERIOUS ADVERSE EVENTS WITH IFN
•
•
•
•
•
•
Seizures
Suicide attempts
Autoimmune disease: SLE, thyroiditis
Hepatic decompensation
Acute renal failure
Sudden death
HUMAN IMMUNODEFICIENCY VIRUS (HIV)
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
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
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
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
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
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
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
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
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
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
REFERENCES
Slides
HIV: The global and Indian scenario
• Dr. Kanupriya Chaturvedi
• Dr. S.K Chaturvedi
Guidelines for the management of hemophilia, 2nd edition
Prepared by the Treatment Guidelines Working Group, on behalf
of the WFH
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