Transcript Varicella-Zoster Virus Disease

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents
Varicella-Zoster Virus 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 July 2013. 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become out of date quickly.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
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VZV Disease: Epidemiology
 Primary VZV = varicella (chickenpox)
 Reactivation of latent VZV results in herpes
zoster (shingles)
 Lifetime risk 15-20%; highest incidence in
immunocompromised and elderly
 Incidence >15-fold higher in HIV infected
compared with general population
 Can occur at any CD4 count; highest frequency
with CD4 count <200 cells/µL
 ART has not been shown to reduce incidence
of zoster in adults
 Rates higher in period immediately after ART
initiation
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VZV Disease: Clinical Manifestations
Varicella: chickenpox
 Lesions evolve rapidly
from macules, papules,
vesicles to pustules and
crusts; successive crops
of new lesions over 2-4
days
 First appears on head,
then trunk, extremities
 Pruritus, fever, headache,
malaise
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VZV Disease: Clinical Manifestations (2)
Varicella: chickenpox
 Illness may be severe in HIV infection
 Visceral dissemination, especially VZV
pneumonitis, may occur
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VZV Disease: Clinical Manifestations (3)
Herpes zoster (shingles):
 Characteristic painful
cutaneous eruption
(papules, then vesicles) in
dermatomal distribution;
often prodrome of pain
 New vesicle formation for
3-5 days, then pustulation
and scabbing; crusts may
peprsist 2-3 weeks
 Extensive skin involvement
and visceral involvement
are rare
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VZV Disease: Clinical Manifestations (4)
Herpes zoster (shingles):
 Recurrence in 20-30% of HIV infected (same
or different dermatome)
 Postherpetic neuralgia in 10-15% of HIVinfected persons
 Complications more common if CD4 count
<200 cells/µL
 Neurologic syndromes: CNS vasculitis, multifocal
leukoencephalitis, ventriculitis, myelitis and
myeloradiculitis, optic neuritis, cranial nerve
palsies, aseptic meningitis
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VZV Disease: Clinical Manifestations (5)
 Progressive outer retinal necrosis may be
seen, almost exclusively with CD4 count
<100 cells/µL
 Acute retinal necrosis: may occur at any
CD4 count
 High rates of visual loss with both
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VZV Disease: Diagnosis
 Clinical diagnosis usually can be made, based
on appearance of lesions
 Retrospective diagnosis of varicella by
documenting seroconversion
 Atypical presentations may be seen in
immunocompromised persons, may be hard to
distinguish from disseminated zoster
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VZV Disease: Diagnosis (2)
 Definitive diagnosis:
 Viral culture, direct fluorescent antigen
testing, or PCR from swabs from fresh lesion,
or tissue biopsy, or scabs
 PCR is most sensitive and specific
 Histopathology and PCR of blood or fluids
(eg, CSF, vitreous humor)
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VZV Disease: Preventing Exposure
 If susceptible (no history of varicella or
zoster, not vaccinated, seronegative for
VZV): avoid exposure to persons with
varicella or zoster
 Susceptible household contacts of
susceptible HIV-infected persons should
be vaccinated
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VZV Disease: Preventing Disease
 Long-term prophylaxis with antiviral drugs is not
recommended
 Vaccination to prevent primary infection
 Live attenuated varicella vaccine may be considered
for HIV-infected, VZV-seronegative persons ≥8 years
of age with CD4 count ≥200 cells/µL (2 doses, 3
months apart)
 No efficacy data in HIV-infected adults and adolescents, but
safe and immunogenic in HIV-infected children with CD4
percentage ≥15%
 If vaccination results in disease caused by vaccine virus, treat
with acyclovir
 Vaccination not recommended if CD4 <200 cells/µL
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VZV Disease: Preventing Disease (2)
 Postexposure prophylaxis to prevent primary
infection:
 Varicella-zoster immune globulin (VariZIG) for VZVsusceptible HIV-infected children and adults
 Give as soon as possible (but ≤10 days) after close
contact with person with active varicella or herpes zoster
 May consider short-term postexposure acyclovir or
valacyclovir beginning 7-10 days after exposure
(not studied in HIV infection)
 Acyclovir 800 mg PO 5 times/day for 5-7 days
 Valacyclovir 1 g PO TID for 5-7 days
 Postexposure varicella vaccination reduces risk of
varicella in immunocompetent children; not studied
in HIV infection
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VZV Disease: Preventing Disease (3)
 Vaccination after exposure
 If postexposure VariZIG has been given, wait
≥5 months before varicella vaccination
 If postexposure acyclovir has been given, wait
≥3 days before varicella vaccination
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VZV Disease: Treatment
Varicella (chickenpox)
 Uncomplicated:
 Preferred
 Valacyclovir 1 g PO TID
 Famciclovir 500 mg PO TID
 Alternative
 Acyclovir 20 mg/kg up to maximum 800 mg PO 5 times
daily
 Duration: 5-7 days
 Severe or complicated:
 Acyclovir 10-15 mg/kg IV Q8H for 7-10 days
 May switch to PO treatment as above after fever
resolves, if no visceral involvement
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VZV Disease: Treatment (2)
Herpes zoster
 Start treatment promptly if diagnosed within 1
week of rash onset, or any time before full
crusting of lesions
 Local dermatomal zoster:
 Preferred
 Valacyclovir 1,000 mg TID
 Famciclovir 500 mg TID
 Alternative
 Acyclovir 800 mg PO 5 times per day
 Duration: 7-10 days (longer if lesions slow to
resolve)
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VZV Disease: Treatment (3)
 Extensive cutaneous lesions or visceral
involvement:
 Acyclovir 10-15 mg/kg IV Q8H, until clinical
improvement
 After clinical improvement and no new cutaneous
lesions, switch to PO therapy as above
 Duration: 10-14 days
 Adjunctive corticosteroid therapy not
recommended (limited data in HIV infection)
 ART optimization is recommended for all VZV
infections that are difficult to treat (eg, retinitis,
encephalitis)
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VZV Disease: Treatment (4)
 Progressive outer retinal necrosis:
 Optimal therapy not defined; poor prognosis for vision
preservation despite antiviral therapy
 Treatment should include at least one IV drug and at
least one intravitreal anti-VZV drug, plus effective ART
 Ganciclovir 5 mg/kg IV Q12H and/or foscarnet 90 mg/kg IV
Q12H PLUS ganciclovir 2 mg/0.05 mL intravitreal twice weekly
and/or foscarnet 1.2 mg/0.05 mL intravitreal twice weekly
 Optimize ART
 Manage in conjunction with an experienced
ophthalmologist
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VZV Disease: Treatment (5)
 Acute retinal necrosis:
 More responsive to antiviral therapy
 Acyclovir 10-15 mg/kg IV Q8H for 10-14 days, followed
by valacyclovir 1 g PO TID for 6 weeks, PLUS
ganciclovir 2 mg/0.05 mL intravitreal twice weekly x 1-2
doses
 Manage in conjunction with an experienced
ophthalmologist
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VZV Disease: Starting ART
 Strongly consider ART initiation in patients with
multiple recurrences of herpes zoster or a
complication of VZV disease
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VZV Disease: Monitoring and Adverse
Events
 IRIS: increased frequency of herpes zoster after
initiation of ART, but clinical presentation and
natural history are not different
 Valacyclovir, acyclovir: renal toxicity at high
dosage
 Monitor renal function for patients on high-dose or
prolonged therapy with IV acyclovir
 High-dose (8 grams/day) valacyclovir may cause
thrombotic thrombocytopenic purpura/hemolytic
uremic syndrome; not reported at lower dosages
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VZV Disease: Treatment Failure
 Suspect drug resistance if lesions do not
start to resolve within 7-10 days of
treatment initiation, or if they evolve to
verrucous or atypical appearance
 Virus culture with susceptibility testing if virus
is isolated
 If proven or suspected acyclovir resistance,
treat with IV foscarnet (alternative: IV
cidofovir)
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VZV Disease: Preventing Recurrence
 Efficacy of long-term antiviral prophylaxis
to prevent recurrence of zoster not
evaluated in HIV infection, not routinely
recommended
 Herpes zoster vaccine: FDA approved for
immunocompetent persons ≥50 years of
age
 Contraindicated if CD4 count <200 cells/µL
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VZV Disease: Considerations in
Pregnancy
 Postexposure prophylaxis:
 Recommended for VZV-susceptible HIV-infected
pregnant women if close contact to person with active
varicella or herpes zoster:
 Varicella-zoster immune globulin (VariZIG)
 Give as soon as possible (but ≤10 days) after exposure
 If acyclovir is used, obtain VZV serology and
discontinue drug if patient is seropositive
 Varicella vaccine and herpes zoster vaccine should
not be given during pregnancy
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VZV Disease: Considerations in
Pregnancy (2)
 Diagnosis as in nonpregnant adults
 Treatment of varicella:
 Uncomplicated: PO acyclovir or valacyclovir
 Severe disease or VZV pneumonitis: hospitalize, IV
acyclovir
 Treatment of zoster:
 PO acyclovir or valacyclovir
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VZV Disease: Considerations in
Pregnancy (3)
 Risk of transmission to fetus if woman has
primary VZV during first half of pregnancy
 Offer detailed ultrasound surveillance for signs of
fetal congenital varicella
 VariZIG recommended to prevent complications in
the mother (not known whether it prevents congenital
varicella syndrome)
 Infants born to women with peripartum varicella
(from 5 days before delivery until 2 days after)
 VariZIG to infant reduces severity and mortality of
neonatal infection
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by Susa Coffey,
MD, for the AETC National Resource Center in
July 2013
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
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