Transcript Varicella-Zoster Virus

Guidelines for Prevention and Treatment of Opportunistic
Infections in HIV-Infected Adults and Adolescents
Viral Infections Slide Set
Prepared by the AETC National Coordinating 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. Certain sections
have been updated to reflect changes in the published
guidelines.
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field of HIV care, this information could become out of date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 Coordinating Resource Center
http://www.aidsetc.org
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Varicella-Zoster Virus
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Epidemiology
Clinical Manifestations
Diagnosis
Preventing Exposure & Disease
Treatment
Monitoring
Preventing Recurrence
Considerations in Pregnancy
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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
Credit: HIV Web Study © 2006, U. of Washington
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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 HIV-infected 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 HIVinfected 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
and updated in May 2015.
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
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