Transcript Document

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents
Hepatitis B Virus Disease Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in April 2015. The intended audience is
clinicians involved in the care of patients with HIV.
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become out of date quickly.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 Resource Center
http://www.aidsetc.org
2
May 2015
www.aidsetc.org
6/05
Hepatitis B Virus Disease:
Epidemiology
 HBV is leading cause of chronic liver disease
worldwide
 Approximately 10% of HIV-infected patients had
chronic HBV infection (globally and in North
America)
 In low-prevalence countries, transmitted primarily
through sexual contact and injection drug use
 More efficient transmission than HIV-1
 In higher-prevalence countries, perinatal
transmission is most common
3
May 2015
www.aidsetc.org
6/05
Hepatitis B Virus Disease:
Epidemiology (2)
 HIV infection increases risk of chronic hepatitis
B after HBV exposure
 HIV/HBV-coinfected patients have higher HBV
DNA levels, greater likelihood of HBe
antigenemia, and increased risk of liver-related
morbidity and mortality
4
May 2015
www.aidsetc.org
6/05
HBV Disease: Epidemiology (3)
 Incubation period
 Exposure to onset of jaundice: 90 days (range 60150 days)
 Exposure to onset of abnormal liver enzymes: 60
days (range 40-90 days)
 Genotypes A-H; GT A is most common in North
America and Western Europe
5
May 2015
www.aidsetc.org
6/05
HBV Disease: Clinical Manifestations
 Acute hepatitis B:
 May be asymptomatic
 Symptoms may include RUQ abdominal pain,
nausea, vomiting, fever, arthralgias, jaundice
6
May 2015
www.aidsetc.org
6/05
HBV Disease: Clinical Manifestations (2)
 Chronic hepatitis B:
 Most have no symptoms or nonspecific
symptoms (eg, fatigue) until development of
cirrhosis and signs of portal hypertension (eg,
ascites, variceal bleeding, coagulopathy,
jaundice, hepatic encephalopathy)
 Hepatocellular carcinoma (HCC) is
asymptomatic in early stages
 Other manifestations: polyarteritis nodosa,
glomerulonephritis, vasculitis
7
May 2015
www.aidsetc.org
6/05
HBV Disease: Diagnosis
 All HIV-infected persons should be tested for
HBV
 Test for HBsAg, HBcAb, and HBsAb
 HBsAb can be detected 4 weeks (range 1-9 weeks)
after exposure anti-HBc IgM usually detectable at
onset of symptoms
 Chronic hepatitis B: HBsAg detected on 2
occasions ≥6 months apart
 Test for HBeAg, anti-HBe, HBV DNA
 HBV DNA and ALT elevation distinguish active from
inactive HBV
8
May 2015
www.aidsetc.org
6/05
HBV Disease: Diagnosis (2)
 Isolated positive anti-HBc:
 May reflect a false-positive result, distant exposure
with loss of anti-HBs, or “occult” chronic HBV infection
 More common in HIV-infected patients, especially if
underlying HCV infection
 Test for HBV DNA: if positive, treat as chronically
infected, if negative, consider susceptible to HBV and
vaccinate accordingly
9
May 2015
www.aidsetc.org
6/05
HBV Disease: Diagnosis (3)
Additional evaluation
 To assess severity and progression of disease,
check ALT, AST, albumin, bilirubin, PT, and
CBC at diagnosis and every 6 months
thereafter
 Transient or persistent elevated ALT levels
caused by many factors, including:
 Discontinuation of HBV therapy, resistance to HBV
therapy, before loss of HBeAg, hepatotoxicity from
HIV or other medications, immune reconstitution,
infection with a new hepatitis virus (HAV, HCV,
delta virus [HDV])
10
May 2015
www.aidsetc.org
6/05
HBV Disease: Diagnosis (4)
Additional evaluation
 Screening for HCC:
 Chronic HBV increases risk of HCC
 Risk and natural history of HBV-related HCC
in HIV-coinfected patents has not been
determined
 Liver imaging recommended every 6 months
if cirrhotic, Asian male > age 40, Asian
female >age 50, sub-Saharan African male
>age 20
11
May 2015
www.aidsetc.org
6/05
HBV Disease: Diagnosis (5)
Additional evaluation
 Assessment of liver fibrosis:
 Important for guiding when to start screening
for esophageal varices and HCC in cirrhotic
patients
 Liver biopsy or noninvasive methods
 Individualize decisions to perform biopsy, especially
as treatment of both HIV and HBV is recommended
for all coinfected patients, using anti-HBV ARVs in
the ART regimen
 Noninvasive methods (eg, transient elastography,
serum biochemical indices): increasing evidence
and experience in HBV
12
May 2015
www.aidsetc.org
6/05
HBV Disease: Preventing Exposure
 Counsel all HIV-infected patients about
reducing risk of exposure to HBV
 Emphasize transmission risks of sharing
needles and syringes, tattooing, body
piercing, unprotected sex
13
May 2015
www.aidsetc.org
6/05
HBV Disease: Preventing Disease
 Vaccinate all HIV-infected patients without
evidence of prior immunity
 Vaccine efficacy higher at CD4 count >350
cells/μL, but do not defer for lower counts
 Decreased response to vaccination in coinfected
patients: check anti-HBs titers 1 month after 3shot series
 If no response, consider revaccination
 Some experts might wait to revaccinate until
sustained CD4 increase with effective ART
14
May 2015
www.aidsetc.org
6/05
HBV Disease: Preventing Disease (2)
 Optimum vaccination strategy not entirely clear,
especially for patients with advanced
immunosuppression
 Schedule of 4 double-dose vaccines yielded higher
anti-HBs titers in 2 studies, and higher overall response
rate in 1
 In 1 study, increased response rate in patients with
CD4 count >350 cells/µL
15
May 2015
www.aidsetc.org
6/05
HBV Disease: Preventing Disease (3)
 Vaccination Schedule
 HBV vaccine IM (Engerix-B 20 mcg/mL or Recombivax
HB 20 mcg/mL) at 0,1, and 6 months, or
 HBV vaccine IM (Engerix-B 40 mcg/mL or Recombivax
HB 20 mcg/mL) at 0, 1, 2, and 6 months, or
 Combined HAV and HBV vaccine (Twinrix) 1 mL as 3dose series at 0,1, and 6 months or as 4-dose series at
days 0, 7, and 21, and at 12 months
 Vaccine non-responders
 Revaccinate with 2nd vaccine series
 If low CD4 count at time of first series, consider
revaccination until sustained increase in CD4 with ART
16
May 2015
www.aidsetc.org
6/05
HBV Disease: Preventing Disease (4)
 HAV-susceptible HIV-infected patients should
receive HAV vaccine
 Check HAV IgG 1 month after vaccination; if negative,
revaccinate when CD4 >200 cells/µL
 All HBV patients should avoid alcohol
consumption
17
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment
 Goals of anti-HBV therapy: reduce morbidity and
mortality
 Treatment indicated for all with HIV/HBV
coinfection, regardless of CD4 count or HBV
treatment status
 Treat with ART that includes 2 drugs active
against both HIV and HBV (ie, tenofovir plus
emtricitabine or lamivudine)
 Regimen should fully suppress both HIV and
HBV
18
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment (2)
 Most drugs active against HBV are also active
against HIV: lamivudine, emtricitabine,
tenofovir, entecavir, probably telbivudine,
adefovir (at full dose)
 HIV may develop resistance to these agents if
they are not coadministered in fully suppressive
ART regimens
 Avoid HBV monotherapy with emtricitabine or
lamivudine – high rates of HBV resistance
19
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment (3)
 Preferred
 ART regimen should include tenofovir 300 mg PO
QD + [emtricitabine 200 mg PO QD or lamivudine
300 mg PO QD] or 2 other drugs active against HBV
(+ additional therapy active against HIV)
 Continue treatment indefinitely
 Alternative
 If patients do not want ART or are unable to take it:
 Treatment indicated when presence of active liver disease,
elevated transaminases, and HBV DNA >2,000 IU/mL, or
significant fibrosis
 Peginterferon-alfa 2a or 2b for 48 weeks
 If tenofovir cannot be used:
 Fully suppressive ART regimen (without tenofovir), plus
entecavir
20
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment (4)
 When changing ART, continue agents active
against HBV to avoid HBV flare, IRIS
 If anti-HBV therapy is discontinued and disease
flares, reintroducing anti-HBV therapy can be
life-saving
21
May 2015
www.aidsetc.org
HBV Disease: Treatment (5)
 HBV/HCV/HIV triple infection:
 Faster progression of liver fibrosis, higher
risk of HCC, increased mortality
 Try to treat both hepatitis viruses, if feasible
 Include anti-HBV therapy with ART;
introduce HCV therapy as needed
 If ART is not desired, consider treatment
with interferon-alfa-based therapy for both
HBV and HCV
22
May 2015
www.aidsetc.org
6/05
HBV Disease: Starting ART
 ART strongly recommended for all with
HIV/HBV coinfection, regardless of ART
 ART that includes agents with activity against
both viruses is recommended
23
May 2015
www.aidsetc.org
6/05
HBV Disease: Monitoring
Monitoring treatment response:
 HBV DNA every 12 weeks
 Complete virologic response: undetectable HBV
DNA at 24-48 weeks
 Nonresponse: <1 log10 copies/mL decrease in
HBV DNA at 12 weeks
 Sustained virologic response: undetectable HBV
DNA 6 months after stopping therapy
 HBeAg every 6 months (if HBeAg positive)
 HBeAg loss, development of HBeAb (uncommon)
 Liver histology, transaminases
24
May 2015
www.aidsetc.org
6/05
HBV Disease: Adverse Events
 Tenofovir
 Renal toxicity; more frequent if underlying renal
disease or prolonged treatment
 Check electrolytes and serum creatinine at
baseline and every 3-6 months; urinalysis every 6
months
 Change to alternative therapy if renal toxicity
occurs
 Dosage adjustment required if used in patients
with baseline renal insufficiency
 Entecavir
 Lactic acidosis reported in patients with cirrhosis
25
May 2015
www.aidsetc.org
6/05
HBV Disease: Adverse Events (2)
 Telbivudine
 CPK elevations and myopathy reported; check CPK
at baseline and every 3-6 months, and if symptoms
occur
 Discontinue if CPK elevation
 Adefovir
 Renal tubular disease at higher dosages;
uncommon at HBV treatment dosage
 Interferon-alfa
 “Flulike” symptoms (fever, myalgia, headache,
fatigue), depression (may be severe), cognitive
dysfunction, cytopenias including CD4 decrease,
retinopathy, neuropathy, autoimmune disorders,
hypo- or hyperthyroidism (monitor TSH)
26
May 2015
www.aidsetc.org
6/05
HBV Disease: Adverse Events (3)
Discontinuation flares
 Discontinuation of nucleos(t)ide analogues
active against HBV (eg, lamivudine, adefovir,
tenofovir, or emtricitabine) associated with
HBV flare in ~30% of cases; may cause
decompensation
 If anti-HBV therapy is discontinued, monitor
transaminases every 6 weeks for 3 months,
then every 3 months
 In case of flare, reinstitute HBV treatment
27
May 2015
www.aidsetc.org
6/05
HBV Disease: IRIS
 Immune reconstitution in HIV/HBV-coinfected
patients can cause rise in transaminases and
symptoms of acute hepatitis flare, usually in first
6-12 weeks after starting ART
 Monitor transaminases monthly for first 3-6
months, then every 3 months
 Flares can be deadly; treat HBV when treating
HIV
 Continue anti-HBV drugs to prevent flares when
switching to ART regimens not containing
lamivudine, emtricitabine, or tenofovir
28
May 2015
www.aidsetc.org
6/05
HBV Disease: IRIS (2)
 If severe flare or suspected HBV drug resistance,
consult with hepatologist
 Distinguishing IRIS and other causes of
transaminase elevation (eg, hepatotoxicity, acute
HCV or HAV, HBV drug resistance, HBeAg
seroconversion) is difficult
 Test HBV DNA, HBeAg, HIV RNA, CD4
 Consider liver histology
 Test for other viral hepatitis as appropriate (hepatitis A,
C, D, E)
 Review medication list
 Review drug and alcohol use
29
May 2015
www.aidsetc.org
6/05
HBV Disease: IRIS (3)
 Hepatotoxicity is associated with all classes of
ARVs, but is uncommon
 Discontinuation of ART usually not necessary unless
symptoms of hypersensitivity are present (fever,
lymphadenopathy, rash), symptomatic hepatitis, or
transaminase elevations >10 times upper limit of
normal
 Jaundice is associated with severe morbidity and
mortality: discontinue offending drug(s)
30
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment Failure
 Treatment failure on nucleos(t)ide analogues:
<1 log10 copies/mL decrease in HBV DNA at
12 weeks in adherent patient, or increase in
HBV DNA >1 log10 above nadir
 Usually attributable to drug resistant HBV;
change in treatment is needed
 Many experts suggest HBV resistance testing
 May help distinguish noncompliance and resistance,
evaluate patients with unclear treatment history,
assess different adefovir resistance pathways, and
predict level of resistance to entecavir
31
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment Failure (2)
 HBV monotherapy should not be used: risk of
resistance mutations to both HBV and HIV
 Lamivudine resistance:
 ~20% per year in HIV/HBV patients treated with
lamivudine alone
 Cross-resistance to emtricitabine, telbivudine,
perhaps entecavir
 If lamivudine-resistant HBV is suspected or
documented, add tenofovir to lamivudine
32
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment Failure (3)
 Treatment failure with tenofovir:
 Consider entecavir (especially if experienced with
lamivudine or emtricitabine)
 In vivo resistance to tenofovir not yet reported
 Treatment failure with entecavir:
 Cross-resistance with lamivudine, emtricitabine,
telbivudine
 Replace entecavir with tenofovir (+/– emtricitabine)
 Failure of response to pegylated interferonalfa:
 Nucleos(t)ide analogues
33
May 2015
www.aidsetc.org
HBV Disease: Treatment Failure (4)
 HBV DNA may decline slowly over
months/years (especially when high before
treatment)
 Patients on adefovir or L-nucleosides with <2
log10 copies/mL decrease in HBV DNA should
be switched to more potent regimen (eg,
tenofovir + emtricitabine or entecavir) because
of risk of resistance
34
May 2015
www.aidsetc.org
6/05
HBV Disease: Treatment Failure (5)
 ESLD management as in HIV-uninfected
patients
 Refer to hepatologist
 IFN contraindicated
 Nucleos(t)ide analogues safe and effective
 HCC screening:
 Imaging every 6-12 months if cirrhosis (ultrasound,
CT, MRI, depending on expertise of the imaging
center and whether patient has cirrhosis)
 Liver transplantation
 Not contraindicated in HIV infection, if on effective
ART
 HBV treatment is needed after transplant
35
May 2015
www.aidsetc.org
6/05
HBV Disease: Preventing Recurrence
 Most patients should continue HBV therapy
(except interferon) indefinitely
 Relapses may occur on therapy, particularly if CD4
count is low
 Hepatitis flare may occur if treatment is stopped
36
May 2015
www.aidsetc.org
6/05
HBV Disease: Considerations in Pregnancy
 All pregnant women should be screened for
HBsAg, HBcAb, and HBsAb and vaccinated
against HBV if sAg negative and sAb negative
 Hepatitis A vaccination can be given
 Acute HBV: treatment is supportive (including
maintaining normal blood glucose levels and
clotting status); higher risk of preterm labor
and delivery
37
May 2015
www.aidsetc.org
6/05
HBV Disease: Considerations in Pregnancy (2)
 Perinatal HBV transmission (including failure of
prophylaxis) correlated with high maternal HBV
DNA levels
 ART including HBV-active drugs recommended
for all coinfected pregnant women
 Drugs with anti-HBV activity will lower HBV levels and
may decrease risk that HBV immune globulin and
vaccine will fail to prevent perinatal HBV transmission
 HBV treatment may lower risk of IRIS-related HBV
flare on ART
 Indefinite treatment is recommended; if ARVs are
discontinued postpartum, monitor LFTs frequently
38
May 2015
www.aidsetc.org
6/05
HBV Disease: Considerations in Pregnancy (3)
 Tenofovir/emtricitabine or tenofovir/lamivudine is
recommended as NRTI backbone for ART in
pregnant HIV/HBV-coinfected women
 More experience in pregnancy with lamivudine
 Entecavir, adefovir, telbivudine: not teratogenic
in animals; limited experience in human
pregnancy
 Consider whether other options are inappropriate; use
only with a fully suppressive ARV regimen
 Interferon should not be use during pregnancy:
antigrowth and antiproliferative effects
39
May 2015
www.aidsetc.org
6/05
HBV Disease: Considerations in Pregnancy (4)
 Infants born to HBsAg+ women: hepatitis B
immune globulin and hepatitis B vaccine within
12 hours of birth
 2nd and 3rd doses of vaccine at 1 and 6 months
40
May 2015
www.aidsetc.org
6/05
Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
41
May 2015
www.aidsetc.org
6/05
About This Slide Set
 This presentation was prepared by Susa
Coffey, MD, for the AETC National
Resource Center in July 2013 and updated
in May 2015.
 See the AETC NRC website for the most
current version of this presentation:
http://www.aidsetc.org
42
May 2015
www.aidsetc.org
6/05