HIV and Hepatitis Co-infection Lucille Sanzero Eller, PhD, RN Associate Professor Rutgers, The State University of New Jersey College of Nursing A Local.

HIV and Hepatitis Co-infectionHIV and Hepatitis Co-infectionLucille Sanzero Eller, PhD, RN

Associate Professor

Rutgers, The State University of New Jersey College of Nursing

A Local Performance Site of the NY/NJ AETC

September 2009

Objectives Objectives (1)(1)

1. Describe transmission, signs and symptoms of Hepatitis A.

2. Describe transmission, signs and symptoms, testing, and treatment of Hepatitis B.

Objectives Objectives (2)(2)

3. Describe transmission, signs and symptoms, testing, and treatment of Hepatitis C.

4. Discuss education of HCV infected patient.

Viral HepatitisViral Hepatitis

Viruses that cause hepatitis include hepatitis A, B, C, D, E, F and G.

Over 90% of hepatitis is caused by viruses A, B or C.

Hepatitis A Virus (HAV)Hepatitis A Virus (HAV)

Transmitted through contact with fecal matter containing the virus

Causes acute hepatitis; symptoms include – fever– malaise– anorexia– nausea– abdominal pain– dark urine– jaundice

Hepatitis A Virus (HAV)Hepatitis A Virus (HAV)

Signs and symptoms usually last <2 months

10% to 15% of those infected have prolonged or relapsing disease (lasts 6-9 months)

Once recovered, those who have had HAV are immune to the disease

Hepatitis B Virus (HBV)Hepatitis B Virus (HBV) (1) (1)

Most common hepatitis virus

A DNA virus from the Hepadnaviridae family

Transmitted through exposure to infected blood and body fluids – perinatal– percutaneous – sexual

Hepatitis B Virus (HBV)Hepatitis B Virus (HBV) (2) (2)

Replication begins with attachment to hepatocytes

Covalently closed circular DNA (CCCDNA), the template for the eventual production of new virus particles, is synthesized

HBV can evade the innate immune response; HBV specific T-cells and trace amounts of HBV DNA in hepatocytes persist many years after recovery from acute HBV

Hepatitis B Virus (HBV)Hepatitis B Virus (HBV) (3) (3)

Symptoms occur in about 70% of patients within 9-21 weeks after exposure to HBV, and include– fever– malaise– anorexia– nausea– abdominal pain– dark urine– jaundice

Hepatitis B Virus (HBV)Hepatitis B Virus (HBV) (4) (4)

Chronic HBV infection (5-10% of those infected) can cause cirrhosis, hepatocellular carcinoma (HCC), and liver failure

The CDC estimates that 1.25 million people in the United States are infected with HBV

HBV vaccine, available since 1982, is recommended for all age groups to

prevent HBV

HIV/HBV Co-infectionHIV/HBV Co-infection

Those co-infected 3 to 6 X more likely to develop chronic HBV than if monoinfected with HBV.

Since HBV genetic material remains in human cells, the virus may be reactivated as immune function deteriorates.

About 25% of people with chronic HBV develop liver damage including cirrhosis or HCC; rate of liver damage is higher and hepatitis B disease progression is more rapid in those with HIV/HBV.

Hepatitis C Virus (HCV) Hepatitis C Virus (HCV) (1)(1)

A single-stranded ribonucleic (RNA) virus Flaviviridae family6 major subtypes; with genotype 1

responsible for more than 70% of infections in U. S.

Most common bloodborne infection in the U.S.

There is no vaccine for HCV

Hepatitis C Virus (HCV) Hepatitis C Virus (HCV) (2)(2)

1.8% of Americans (3.9 million) infected with HCV; most (2.7 million) are chronically infected (50-80% of those infected) (CDC, 2006)

Prevalence estimated from the third National Health and Nutrition Examination Survey – civilian, non-institutionalized U.S. population

NHANES III survey did not include incarcerated, homeless– these groups have high prevalence of HCV, so

estimate is conservative

Hepatitis C Virus (HCV) Hepatitis C Virus (HCV) (3)(3)

80% of those infected are asymptomatic

50-80% of immunocompetent people who become infected become chronically infected

Hepatitis C Virus (HCV) Hepatitis C Virus (HCV) (4)(4)

Among the chronically infected– 60% to 70% develop chronic hepatitis– 10% to 20% develop cirrhosis over a

period of 20-30 years– 1% to 5% develop HCC – End-stage liver disease (ESLD) and HCC

cause between 10,000 and 12,000 deaths per year in the U.S.

Sources of Infection with HCVSources of Infection with HCV (1) (1) (CDC, 2006)(CDC, 2006)

Sources of Infection with HCVSources of Infection with HCV (2) (2)

60% of cases due to past or current IDU

60% to 80% of IDUs injecting drugs for at least 5 years are HCV infected vs. 30% of them HIV infected

Risk of HCV transmission through sexual

exposure is low However, general population’s frequency of sexual

behaviors, plus prevalence of HCV, explains the high proportion (15%) of HCV transmitted through sexual exposure

Sources of Infection with HCVSources of Infection with HCV (3) (3)

10% due to transfusion (prior to screening) Viral inactivation techniques for clotting factors

introduced in 1985 (Factor VIII); 1987 (Factor IX)

By 2001, risk of infection from a unit of transfused blood less than one per million transfused units

Currently, all immune globulin products undergo a virus inactivation procedure or test negative for HCV prior to release

Sources of Infection with HCVSources of Infection with HCV (4) (4)

5% of cases due to exposures from hemodialysis employment in the health care field birth to an HCV-infected mother

10% of cases have no recognized source of infection

HIV/HCV Co-infection HIV/HCV Co-infection (1)(1)

HIV increases the levels of HCV viremia and progression to cirrhosis, liver failure and death

Risk of liver-related mortality in the co-infected is related to HIV viral load and CD4 count

HIV/HCV Co-infection HIV/HCV Co-infection (2)(2)

Study compared 265 with HCV/HIV, 251 with HCV alone, 227 with HIV alone

Mortality over a 3-year period was: 17% in those HIV/HCV co-infected 9% in those with HIV alone 6% in those with HCV alone

In co-infected, mortality varied by race Whites 31% Blacks 15% (Merriman et al., 2006)

HIV/HCV Co-infection HIV/HCV Co-infection (3)(3)

Effects of HCV co-infection on HIV progression unknown accelerated clinical progression of HIV-1

(Mathurin et al., 1998; Tong, El-Farra, Reikes & Co, 1995) impaired CD4-cell recovery and faster HIV

disease progression in HCV co-infected patients despite their receiving ART (Grueb, 2000)

no impact on CD4 count, viral load, HIV progression or survival (Hayashi et al, 1991; Thomas et al., 1996; Mayor, 2006; Merriman et al., 2006)

HIV/HBV Co-infection HIV/HBV Co-infection

Mortality Rates:

14.2/1000 in HIV/HBV co-infected 1.7/1000 in HIV monoinfected 0.8/1000 in HBV monoinfected

HBV TestingHBV Testing

Recommended for specific at-risk groups men who have sex with men injection drug users patients on dialysis people with HIV pregnant women families, household members and sexual

contacts of HBV-infected persons

HBV Testing- Serologic MarkersHBV Testing- Serologic Markers (1) (1)

Evaluation includes serologic testing for viral markers HBsAg: hepatitis B surface antigen; indicates

acute or chronic HBV infection

HBsAb: antibody to HBV surface antigen, a marker of HBV immunity

HBeAg: usually positive when HBV is present; a marker of high infectivity

HBV Testing- Serologic MarkersHBV Testing- Serologic Markers (2) (2)

Evaluation includes serologic testing for viral markers Anti-HBc: antibody to the hepatitis B core

antigen; indicates past infection, either acute or chronic

Anti-HBe: antibody to the hepatitis B e antigen. In those recovered from acute or chronic HBV infection, anti-HBe, anti-HBc and anti-HBs will be present

HBV TestingHBV Testing

HBV DNA Tests Used in conjunction with serologic testing for

patients being considered for treatment and to evaluate response to treatment

An unamplified HBV DNA assay with detection limits of 105 to 106 copies/mL is the diagnostic criterion for chronic HBV

Liver biopsy or alanine aminotransferase (ALT) are recommended to assess the degree of necroinflammation

HBV Treatment HBV Treatment (1)(1)

Goals of treatment viral suppression remission of liver disease

HBV Treatment HBV Treatment (2)(2)

First line treatment options interferons

IFN--2a and 2b Pegylated IFN--2a and 2b

nucleoside/nucleotide analogs lamivudine adefovir dipivoxil entecavir telbivudine tenofovir

HBV Treatment HBV Treatment (3)(3)

Emtricitabine is effective against both HBV and HIV but not yet FDA approved for HBV infection

Recent data indicate that entecavir has HIV activity and should not be used as monotherapy for HBV in HIV-infected patients who are not taking other ARVs

HBV Treatment HBV Treatment (4)(4)

Indicators of adequate response to treatment undetectable serum HBV DNA HBeAg loss or seroconversion improved liver histology on biopsy

HIV/HBV Co-infection Treatment HIV/HBV Co-infection Treatment (1)(1)

If need to treat HIV in an HIV/HBV co-infected patient: NRTI backbone of an antiretroviral regimen could be tenofovir + emtricitabine tenofovir + lamivudine

Monotherapy of HBV with lamivudine, emtricitabine, or tenofovir should be avoided if possible because of risk of resistance

HIV/HBV Co-infection Treatment HIV/HBV Co-infection Treatment (2)(2)

If need to treat HIV and HBV combination of tenofovir + lamivudine or

tenofovir + emtricitabine should be considered as first-choice NRTI backbones

additional options include entecavir only in combination with one of the three nucleosides with activity against both viruses

use of lamivudine, emtricitabine, or tenofovir as the only active anti-HBV agent should be avoided because of risk of HIV resistance

HIV/HBV Co-infection Treatment HIV/HBV Co-infection Treatment (3)(3)

Treatment of HBV and not HIV Pegylated interferon-alpha, one option, does not

lead to development of drug-resistant HIV or HBV mutations

Adefovir dipivoxil is active against HBV but not against HIV at the 10 mg dose; however, a theoretical risk for development of HIV mutants exists, because it is related to tenofovir.

use of emtricitabine, lamivudine, or tenofovir without a full HAART regimen should be avoided because of the rapid development of drug-resistant HIV mutations

HIV/HBV Co-infection Treatment HIV/HBV Co-infection Treatment (4)(4)

If there is a need to discontinue lamivudine, tenofovir, or emtricitabine

Monitor clinical course with frequent liver function tests, and consider the use of adefovir dipivoxil or entecavir to prevent flares, especially in patients with marginal hepatic reserve

HCV TestingHCV Testing

Routinely test all HIV-infected patients First use the enzyme immunoassay (EIA) test

for anti-HCV antibodies if EIA is positive, use an HCV RNA assay to

document viremia

Note: Patients co-infected with HCV/HIV may have negative HCV antibody tests because of immunosuppression

HCV RNA Assays HCV RNA Assays (1)(1)

Used to confirm results of less sensitive HCV antibody assay

qualitative and quantitative assays to detect HCV RNA use target amplification (PCR, TMA) or signal amplification (branched DNA) techniques

HCV RNA can be used to predict and monitor response to treatment

results of different assays are not easily compared, so use same assay to monitor response to treatment

HCV RNA Assays HCV RNA Assays (2)(2)

HCV RNA assays can be used in those with HIV to establish HCV infection within 2 weeks of infection

HCV RNA assays can detect HCV RNA in most patients with chronic HCV

Liver biopsyLiver biopsy

Recommended by most experts to stage degree of hepatic necrosis, inflammation and fibrosis

Used to determine need for HCV treatment

False negatives can occur in 10%-30% of cases (due to small size of biopsy specimens and heterogeneous

distribution of liver fibrosis)

HCV RNA GenotypingHCV RNA Genotyping

6 known genotypes of HCV Genotype 1 most common in the U.S . Use of genotyping

to determine the type and duration of treatment to assess likelihood of response to therapy

Patients with genotype 1 have much lower rates of response to treatment than those with genotype 2 or 3

ALT and ASTALT and AST

ALT- alanine aminotransferase AST- aspartate aminotransferase

Markers of hepatic cell damage Not sensitive or specific markers of disease

progression Can be useful in monitoring treatment effects

HCV Treatment GoalsHCV Treatment Goals

Goals of treatment for chronic HCV Viral eradication (undetectable viral load) Prevent progression of liver disease

Best indicator of treatment is sustained virologic response (SVR)

Sustained Virologic ResponseSustained Virologic Response

Serum HCV RNA is undetectable based on a qualitative HCV RNA assay with lower limit of detection of 50 IU/mL or less at 24 weeks after treatment ends

HCV Treatment HCV Treatment (1)(1)

Combination therapy with pegylated interferon (PEG-IFN) alfa plus ribavirin is most effective treatment for HCV in patients with or without HIV; with this treatment: 50% of HCV genotype 1 monoinfected patients

achieve HCV viral clearance HCV/HIV-coinfected genotype 1 patients have a

22%-29% SVR rate if treated for 48 weeks with other genotypes, there is a 55% SVR rate

HCV Treatment HCV Treatment (2)(2)

Ribavirin is teratogenic

Both men and women must use contraception during and for 6 months after treatment with ribavirin

HCV Treatment HCV Treatment (3)(3)

Those who are not candidates for treatment for HCV include: those actively using alcohol those with untreated depression those with renal disease those with advanced cirrhosis pregnant women

(NIH, 2002)

HCV Treatment HCV Treatment (4)(4)

Although pregnant women and persons with active alcohol use should not receive HCV treatment, certain individuals with renal disease, depression, injection drug use, and lower degrees of hepatic fibrosis can be considered for HCV treatment

Considerations in HCV Treatment Considerations in HCV Treatment (1)(1)

Ribavirin should not be given with didanosine; drug-drug interactions can cause pancreatitis and lactic acidosis

Some NRTIs and all NNRTIs and PIs can be hepatotoxic, so transaminase levels should be monitored

(Panel on Clinical Practices for Treatment of HIV Infection, 2008)

Considerations in HCV Treatment Considerations in HCV Treatment (2)(2)

Higher rates of anemia are associated with zidovudine combined with ribavirin

Growth factors may be needed manage IFN-associated neutropenia and ribavirin-associated anemia

(Panel on Clinical Practices for Treatment of HIV Infection, 2008)

Considerations in HCV Treatment Considerations in HCV Treatment (3)(3)

In HIV/HCV co-infected

Decision when to initiate HCV treatment is case by case

Initiating HIV treatment first can increase CD4 counts, may improve response to HCV therapy

Initiating HCV treatment first (in those with high CD4 counts and low viral load) can simplify treatment and improve ART tolerability

HCV Patient Education HCV Patient Education (1)(1)

To avoid infecting others avoid sharing: toothbrushes dental appliances razors sex toys tattoo equipment injection equipment personal care items that may have blood on

them Educate and encourage use of safer sex

practices

HCV Patient Education HCV Patient Education (2)(2)

Recommend alcohol abstinence before and during antiviral therapy Alcohol is a cofactor in progression of liver

disease to cirrhosis and HCC Alcohol use during therapy adversely affects

response to treatment

Assess readiness and refer to alcohol treatment if appropriate

HCV Patient Education HCV Patient Education (3)(3)

Assess readiness and counsel regarding drug treatment programs if using injection drugs

If drug treatment is not an option, provide risk reduction education cleansing of injection equipment provide patient with a source of clean, single-

use needles if possible

HCV Patient Education HCV Patient Education (4)(4)

Instruct to avoid exposure to hepatotoxins, including hepatotoxic medications (eg, acetaminophen in large doses, fluconazole, and isoniazid)

Instruct to consult a health care professional before taking any new medicines, including over-the-counter, alternative or herbal products

HCV Patient Education HCV Patient Education (5)(5)

Instruct to avoid exposure to environmental toxins solvents paint thinners pesticides

If using toxic chemicals work in a well-ventilated area wear gloves wear a protective face mask

HCV Patient Education HCV Patient Education (6)(6)

If patient is pregnant or considering pregnancy, discuss ways to decrease the infection risk for the baby

HCV Patient Education HCV Patient Education (7)(7)

Recommended Vaccinations:

Anyone with HCV should be tested for immunity to HAV and HBV; those not immune should receive the vaccines

All persons with chronic liver disease should be vaccinated annually against influenza and should receive

pneumoccocal vaccine

HCV Patient Education HCV Patient Education (8)(8)

Side effects of interferon (fatigue, depression, confusion) can interfere with appointment and medication adherence

Provide support to maximize adherence Conduct ongoing assessments and treat and

refer as needed for depression

HCV Patient Education HCV Patient Education (9)(9)

To reduce adverse effects instruct patients to: increase fluid intake eat small, frequent, well-balanced meals exercise as tolerated get adequate sleep and rest avoid crowds to prevent infection take interferon injections before going to bed so

will sleep through some of the adverse effects

Key Points Key Points (1)(1)

1. Hepatitis A is transmitted through contact with infected fecal matter.

2. Hepatitis B and C are transmitted through exposure to infected blood and body fluids.

3. Chronic HBV (5-10% of those infected) and chronic HCV infection (50-80% of those infected) can cause cirrhosis, HCC and liver failure.

Key Points Key Points (2)(2)

4. HBV Testingi. serologic testing for viral markers

recommended for men who have sex with men injection drug users patients on dialysis people with HIV pregnant women families, household members and sexual

contacts of HBV-infected persons

Key Points Key Points (3)(3)

4. HBV Testing (cont.)

ii. HBV DNA tests used for patients being considered for treatment and to evaluate response to treatment

iii. Liver biopsy and ALT to assess degree of necroinflammation

Key Points Key Points (4)(4)

5. HBV Treatment

A. First line treatment options

1) Interferons

2) Nucleoside/nucleotide analogs

B. Indicators of adequate response

1) undetectable serum HBV DNA

2) HBeAg loss or seroconversion

3) improved liver histology on

biopsy

Key Points Key Points (5)(5)

6. HCV Testingi. Test all HIV+ patients

ii. Use EIA for anti-HCV antibodies

iii. If EIA positive, confirm with HCV RNA assay to document viremia

iv. HCV genotying to determine type/duration of treatment

v. Liver biopsy to determine need for treatment

Key Points Key Points (6)(6)

7. HCV Treatmenti. PEG-IFN alfa plus ribavirin

ii. Educate patients and assess readiness for treatmenti. avoid infecting others

ii. avoid alcohol and drugs

iii. avoid hepatotoxins

iv. receive HAV and HBV vaccines