Tonia Poteat, MMSc, PA-CThursday, June 5, 2008

ECHO Webinar

Tonia Poteat, MMSc, PA-CThursday, June 5, 2008

ECHO Webinar

HIV and Viral HepatitisIn Oral Health SettingsHIV and Viral HepatitisIn Oral Health Settings

ObjectivesObjectives

Review basics of viral hepatitis and HIV co-infection Transmission and prevention Disease progression/oral manifestations Treatment (including drug interactions)

Describe post-exposure prophylaxis recommendations

Review basics of viral hepatitis and HIV co-infection Transmission and prevention Disease progression/oral manifestations Treatment (including drug interactions)

Describe post-exposure prophylaxis recommendations

HIV

HIV TransmissionHIV Transmission

Transmission Fluids Blood Semen Vaginal secretions Breast milk

Ports of Entry Broken skin Mucus membranes

Prevention Universal precautions Safer sex Post-exposure prophylaxis

Transmission Fluids Blood Semen Vaginal secretions Breast milk

Ports of Entry Broken skin Mucus membranes

Prevention Universal precautions Safer sex Post-exposure prophylaxis

Periodontal Disease in HIV Disease

Oral Candidiasis (Thrush)

Oral Hairy Leukoplakia

Credit: I-TECH

Bleeding gumsBleeding gums

http://www.perio.org/consumer/children.htm

Idiopathic Thrombocytopenic PurpuraIdiopathic Thrombocytopenic Purpura

Pathogenesis unknown. Pt often asx

Sx: ecchymosis, petechiae, purpura, abnl menses, blood in urine or stool, epistaxis, bleeding gums

CBC, PT/PTT are normal

May or may not have anti-platelet antibodies

Tx: HAART, steroids, WinRho, splenectomy

Avoid NSAIDS, razor shaving, mild trauma

Pathogenesis unknown. Pt often asx

Sx: ecchymosis, petechiae, purpura, abnl menses, blood in urine or stool, epistaxis, bleeding gums

CBC, PT/PTT are normal

May or may not have anti-platelet antibodies

Tx: HAART, steroids, WinRho, splenectomy

Avoid NSAIDS, razor shaving, mild trauma

Low platelets may also be a manifestation of advanced

liver disease!

Comparison of Viral HepatitidesComparison of Viral Hepatitides

Virus Type Transmission Cirrhosis Notes

A RNA Fecal-oral No Vaccination available No chronic form

B DNA Blood, sex, perinatal

Yes Vaccination available Associated with HCC

C RNA Blood, sex Yes Most common reason for liver transplant

D RNA Blood, sex Yes Dependent on HBV infection

E RNA Fecal-oral No Most dangerous in pregnancy

G RNA Blood ? Unknown relevance

Virus Type Transmission Cirrhosis Notes

A RNA Fecal-oral No Vaccination available No chronic form

B DNA Blood, sex, perinatal

Yes Vaccination available Associated with HCC

C RNA Blood, sex Yes Most common reason for liver transplant

D RNA Blood, sex Yes Dependent on HBV infection

E RNA Fecal-oral No Most dangerous in pregnancy

G RNA Blood ? Unknown relevance

HEPATITIS A

Hepatitis AHepatitis A

Transmission fecal/oral

High Risk day care, institutions, military, MSM

Incubation period last 2 - 4 weeks transmission occurs during this

asymptomatic time Laboratory diagnosis

HAV IgM indicates current or recent infection

HAV IgG indicates past infection or vaccination

Transmission fecal/oral

High Risk day care, institutions, military, MSM

Incubation period last 2 - 4 weeks transmission occurs during this

asymptomatic time Laboratory diagnosis

HAV IgM indicates current or recent infection

HAV IgG indicates past infection or vaccination

JaundiceJaundice

http://www.gideononline.com/blog/2007/05/01/easier-diagnosis-with-symptom-images/

Hepatitis AHepatitis A

Infection is self-limited (8-12 weeks) jaundice signals end of infectious period vast majority recover with lifelong

immunity (98-99%) Treatment is supportive

post exposure immune globulin available must give within 1-2 weeks of exposure

Vaccination recommended: travelers to endemic areas, people with

CLD (including HCV), MSM, day care workers, food handlers, sewage workers,

Prevention is key: WASH YOUR HANDS!!!

Infection is self-limited (8-12 weeks) jaundice signals end of infectious period vast majority recover with lifelong

immunity (98-99%) Treatment is supportive

post exposure immune globulin available must give within 1-2 weeks of exposure

Vaccination recommended: travelers to endemic areas, people with

CLD (including HCV), MSM, day care workers, food handlers, sewage workers,

Prevention is key: WASH YOUR HANDS!!!

US Prevalence 1 million 4 million 1.25 million

Annual US Deaths 16,000 10,000 6,000

GeneticMaterial RNA RNA DNA

PercutaneousTransmission

Risk

0.3% 3% 30%

HIV HCV HBVHIV HCV HBV

HIV and Chronic Viral HepatitisHIV and Chronic Viral Hepatitis

HEPATITIS B

Hepatitis BHepatitis B

Transmission sexual, blood, perinatal, occupational more infectious than HIV

can survive on surfaces 1 wk or more

High Risk health care workers unprotected sex (including oral) IN and Injection drug use

blood supply screened

Incubation period 4 weeks to 6 months average 12 weeks

Transmission sexual, blood, perinatal, occupational more infectious than HIV

can survive on surfaces 1 wk or more

High Risk health care workers unprotected sex (including oral) IN and Injection drug use

blood supply screened

Incubation period 4 weeks to 6 months average 12 weeks

Hepatitis BHepatitis B

Acute Symptoms last 2 – 10 weeks 90% recover with lifelong immunity

50-80% among PLWHIV Treatment is supportive HBsAg resolves within 6 months

Chronic Persistent HBsAg > 6 months 10-20% will develop cirrhosis 25% of these will decompensate 6-15% of those with chronic disease will

develop hepatocellular carcinoma

Acute Symptoms last 2 – 10 weeks 90% recover with lifelong immunity

50-80% among PLWHIV Treatment is supportive HBsAg resolves within 6 months

Chronic Persistent HBsAg > 6 months 10-20% will develop cirrhosis 25% of these will decompensate 6-15% of those with chronic disease will

develop hepatocellular carcinoma

HBV/HIV Co-infectionHBV/HIV Co-infection

Co-infected patients have Higher HBV DNA levels Lower ALT Lower rate of

seroconversion Higher risk of cirrhosis Immune Reconstitution Reactivation with

stopping ART

Hepatitis B vaccination recommended for all patients with HIV

Co-infected patients have Higher HBV DNA levels Lower ALT Lower rate of

seroconversion Higher risk of cirrhosis Immune Reconstitution Reactivation with

stopping ART

Hepatitis B vaccination recommended for all patients with HIV

Liver Mortaility by HIV and HBV Status

0 0.8 1.7

14.1

0

5

10

15

NoHIV orHBV

HBVonly

HIVonly

HIVandHBV

Thio C et al. Lancet 2002;360:9349.

Chronic Hepatitis B: Treatment GoalsChronic Hepatitis B: Treatment Goals

Normalize transaminases

Eliminate/Suppress HBV replication

Loss of HBsAg with seroconversion to HBsAb (anti-HBs)

Prevent progression to ESLD and HCC

Normalize transaminases

Eliminate/Suppress HBV replication

Loss of HBsAg with seroconversion to HBsAb (anti-HBs)

Prevent progression to ESLD and HCC

HBV Treatment Options in HIVHBV Treatment Options in HIV

DrugHIV Activity?

HBV potency

Resistance barrier Notes

Peg-IFN Yes High No Tx x 12 moNo use in ESLD

Lamivudine(Epivir HB)

Yes Middle Low High tolerability

Adefovir(Hepsera)

No Middle Middle Good for ESLD and 3TC failures

Entecavir(Baraclude)

YES! High High Ok for 3TC failuresTolerable

Telbivudine(Tyzeka)

No High Middle? No studies in HIV

Tenofovir*(Viread)

Yes High High Good for 3TC and adefovir failures

Emtricitabine*(Emtriva)

Yes Middle Low TDF/FTC coformula3TC equivalent

www.medscape.comwww.medscape.com

HBV Treatment in HIV PatientsHBV Treatment in HIV Patients

2008 DHHS Guidelines lists Hepatitis B

as an indication for initiation of antiretroviral therapy

If ARV naïve and require HIV treatment Tenofovir + emtricitabine or lamivudine

Individualization of therapy required in ARV experienced patients

2008 DHHS Guidelines lists Hepatitis B

as an indication for initiation of antiretroviral therapy

If ARV naïve and require HIV treatment Tenofovir + emtricitabine or lamivudine

Individualization of therapy required in ARV experienced patients

HIV-HBV consensus panel. AIDS 2005

DHHS Guidelines 2008

HIV-HBV consensus panel. AIDS 2005

DHHS Guidelines 2008

Hepatitis B: Prevention & Care Hepatitis B: Prevention & Care

PREVENTION Vaccination Universal Precautions Safer Sex

CARE Vaccination against Hepatitis A Avoidance of ETOH Caution with hepatotoxic medications Screening for HCC (+/- esophogeal

varices) for cirrhotics, high HBV DNA, >40yo, FH

PREVENTION Vaccination Universal Precautions Safer Sex

CARE Vaccination against Hepatitis A Avoidance of ETOH Caution with hepatotoxic medications Screening for HCC (+/- esophogeal

varices) for cirrhotics, high HBV DNA, >40yo, FH

HEPATITIS C

Risk factors for Hepatitis C infection

20%

10%

5%

55%

10%

IVDU CocaineExposure to infected sex partner or multiple partnersOccupational, hemodialysis, household, perinatal

No recognized source

http://www.cdc.gov/ncidod/diseases/hepatitis/c_training/edu/transmission modes; 2000

SymptomsSymptoms

Often none until decompensation

Otherwise symptoms are vague: Fatigue Mild RUQ discomfort Nausea Poor appetite Muscle and joint pains

Often none until decompensation

Otherwise symptoms are vague: Fatigue Mild RUQ discomfort Nausea Poor appetite Muscle and joint pains

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Extrahepatic Manifestations of Hepatitis CExtrahepatic Manifestations of Hepatitis C

Hematologic: Cryoglobulinemia Lymphoma

Rheumatologic: rheumatoid arthritis

Renal: Glomerulonephritis Dermatologic:

Porphyria cutanea tarda Cutaneous necrotizing vasculitis Lichen planus

CNS: depression Systemic: fatigue

Hematologic: Cryoglobulinemia Lymphoma

Rheumatologic: rheumatoid arthritis

Renal: Glomerulonephritis Dermatologic:

Porphyria cutanea tarda Cutaneous necrotizing vasculitis Lichen planus

CNS: depression Systemic: fatigue

Management of Hepatitis C. NIH Consensus Statement, 2002.

Natural History of Hepatitis C Natural History of Hepatitis C Virus (HCV) InfectionVirus (HCV) Infection

Exposure(Acute phase)

Resolved Chronic

CirrhosisStable

SlowlyProgressive

HCCTransplant

Death

20% (17)

15% (15) 85% (85)

25% (4)

80% (68)

75% (13)

HIV and Alcohol

HCC = hepatocellular carcinoma.

Alter MJ. Semin Liver Dis. 1995;15:5-14.NIH Consensus Statement. Management of hepatitis C. National Institutes of Health; March 24-26, 1997.

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HIV/HCV Co-infectionHIV/HCV Co-infection

Impact of HIV on HCV HCV Ab may be negative if low CD4 Higher HCV viral loads Accelerates progression to cirrhosis Increases risk of perinatal transmission

Impact of HCV on HAART Choices Higher risk of hepatotoxicity from HAART All classes associated with liver toxicity Hepatotoxic potential varies for each

individual antiretroviral medication

Impact of HIV on HCV HCV Ab may be negative if low CD4 Higher HCV viral loads Accelerates progression to cirrhosis Increases risk of perinatal transmission

Impact of HCV on HAART Choices Higher risk of hepatotoxicity from HAART All classes associated with liver toxicity Hepatotoxic potential varies for each

individual antiretroviral medication

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Hepatitis C LabsHepatitis C Labs

HCV antibody for screening

99% sensitive and specific

May be negative if low CD4,

HCV RNA by PCR:

qualitative PCR (dx and SVR)

quantitative PCR (likelihood of SVR)

Liver Enzymes

Do not correlate with extent of liver damage

Most patients have minimally elevated or normal liver enzymes

HCV antibody for screening

99% sensitive and specific

May be negative if low CD4,

HCV RNA by PCR:

qualitative PCR (dx and SVR)

quantitative PCR (likelihood of SVR)

Liver Enzymes

Do not correlate with extent of liver damage

Most patients have minimally elevated or normal liver enzymes

34

HCV Treatment: Standard of CareHCV Treatment: Standard of Care

Pegylated Interferon Pegasys 180 mcg/week (FDA approved for

treatment of HIV/HCV co-infection) Peg-Intron 1.5 mcg/kg/week

Ribavirin Weight based dosing (500-600mg BID) Generic available Rebetol capsules Copegus tablets

All HIV co-infected patients should be treated for at least 48 weeks if . . . 2 log reduction in HCV RNA at 12 weeks, and HCV RNA undetectable at 24 weeks

Pegylated Interferon Pegasys 180 mcg/week (FDA approved for

treatment of HIV/HCV co-infection) Peg-Intron 1.5 mcg/kg/week

Ribavirin Weight based dosing (500-600mg BID) Generic available Rebetol capsules Copegus tablets

All HIV co-infected patients should be treated for at least 48 weeks if . . . 2 log reduction in HCV RNA at 12 weeks, and HCV RNA undetectable at 24 weeks

Goals of treatmentGoals of treatment

Stable HIV disease with intact immune function (CD4 > 200) Goal to eradicate HCV

Advanced fibrosis: Stage 3 or 4 Goal to delay progression

Recurrent ARV-associated hepatoxicity Permit HAART treatment

Stable HIV disease with intact immune function (CD4 > 200) Goal to eradicate HCV

Advanced fibrosis: Stage 3 or 4 Goal to delay progression

Recurrent ARV-associated hepatoxicity Permit HAART treatment

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Contraindications to IFN/RBVContraindications to IFN/RBV

Absolute Contraindications pregnancy decompensated liver disease unstable heart disease sickle cell

Relative contraindications severe psychiatric problems active substance abuse untreated anemia/neutropenia severe comorbid diseases

Absolute Contraindications pregnancy decompensated liver disease unstable heart disease sickle cell

Relative contraindications severe psychiatric problems active substance abuse untreated anemia/neutropenia severe comorbid diseases

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Adverse Effects: InterferonAdverse Effects: Interferon

IFN related fatigue, flu

syndrome bone marrow depression, lability injection site

reaction alopecia, insomnia anorexia/weight loss thyroid dysfunction neuropathy retinopathy

IFN related fatigue, flu

syndrome bone marrow depression, lability injection site

reaction alopecia, insomnia anorexia/weight loss thyroid dysfunction neuropathy retinopathy

Management light exercise, H20 pre-injection Tylenol Epoetin, GCSF anti-depressants small, frequent

meals night time dosing most are self limited

or resolve after treatment is stopped

Management light exercise, H20 pre-injection Tylenol Epoetin, GCSF anti-depressants small, frequent

meals night time dosing most are self limited

or resolve after treatment is stopped

38

Adverse Effects: RibavirinAdverse Effects: Ribavirin

RBV related hemolytic anemia pruritic rash nausea dyspnea, dry cough teratogenic in vitro interactions

with other nucleosides increases DDI decreases AZT,

D4T

RBV related hemolytic anemia pruritic rash nausea dyspnea, dry cough teratogenic in vitro interactions

with other nucleosides increases DDI decreases AZT,

D4T

Management dose reduction or

epoetin alfa antihistamines,

topicals take with food effective birth

control careful monitoring

for lactic acidosis and HIV viral breakthrough

Management dose reduction or

epoetin alfa antihistamines,

topicals take with food effective birth

control careful monitoring

for lactic acidosis and HIV viral breakthrough

39

Ribavirin Drug InteractionsRibavirin Drug Interactions

Anti-HIV synergy with DDI Increases intracellular levels Case reports of fatal pancreatitis and

lactic acidosis. FDA issued warning

Care with overlapping toxicities Anemia with ZDV Weight loss/lipoatrophy with D4T

Data from CROI 2008 Higher rates of SVR with TDF

compared to ABC and ZDV

Anti-HIV synergy with DDI Increases intracellular levels Case reports of fatal pancreatitis and

lactic acidosis. FDA issued warning

Care with overlapping toxicities Anemia with ZDV Weight loss/lipoatrophy with D4T

Data from CROI 2008 Higher rates of SVR with TDF

compared to ABC and ZDV

CROI 2008Salmon-Céron. Lancet. 2001;357:1803. Hoggard. AAC. 1995;39(6):1376.

HCV: Prevention and CareHCV: Prevention and Care

PREVENTION Universal precautions Safer sex/Harm reduction No vaccine available

CARE

Vaccination against Hepatitis A and B

Avoid ETOH

Care with hepatotoxic medications

Screen for HCC if cirrhotic

PREVENTION Universal precautions Safer sex/Harm reduction No vaccine available

CARE

Vaccination against Hepatitis A and B

Avoid ETOH

Care with hepatotoxic medications

Screen for HCC if cirrhotic

PEP

Hepatitis BHepatitis B

MMWR, June 29, 2001

Hepatitis CHepatitis C

No evidence of efficacy of immune globulin

No CDC recommendations

Evidence of improved SVR for those starting interferon based treatment early after infection early

No evidence of efficacy of immune globulin

No CDC recommendations

Evidence of improved SVR for those starting interferon based treatment early after infection early

HIV PEP: ConsiderationsHIV PEP: Considerations

Risk level of exposure Concomitant conditions Drug-drug interactions Resistance Tolerability Start as soon as possible Continue for 4 weeks

Risk level of exposure Concomitant conditions Drug-drug interactions Resistance Tolerability Start as soon as possible Continue for 4 weeks

HIV: Mucus Membrane ExposureHIV: Mucus Membrane Exposure

MMWR, Sept 30, 2005

HIV: Needlestick ExposureHIV: Needlestick Exposure

MMWR, Sept 30, 2005

Post-exposure ProphylaxisPost-exposure Prophylaxis

National Clinician’s Consultation Linehttp://www.nccc.ucsf.edu/

Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxishttp://www.cdc.gov/MMWR/preview/MMWRhtml/rr5011a1.htm

Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxishttp://www.cdc.gov/mmwR/preview/mmwrhtml/rr5409a1.htm

National Clinician’s Consultation Linehttp://www.nccc.ucsf.edu/

Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxishttp://www.cdc.gov/MMWR/preview/MMWRhtml/rr5011a1.htm

Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxishttp://www.cdc.gov/mmwR/preview/mmwrhtml/rr5409a1.htm

Helpful ResourcesHelpful Resources

www.HIVandHepatitis.com

Hepatitis Info 1-800-223-0179

http://www.hivdent.org/

www.HIVandHepatitis.com

Hepatitis Info 1-800-223-0179

http://www.hivdent.org/