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 Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Viral Infections Slide Set

2 July 2013www.aidsetc.org These slides were developed using recommendations published in July 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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 About This Presentation

3 July 2013www.aidsetc.org  Epidemiology  Clinical Manifestations  Diagnosis  Preventing Exposure & Disease  Treatment  Monitoring  Preventing Recurrence  Considerations in Pregnancy Varicella-Zoster Virus

4 July 2013www.aidsetc.org  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 VZV Disease: Epidemiology

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 5 July 2013www.aidsetc.org Credit: HIV Web Study © 2006, U. of Washington

6 July 2013www.aidsetc.org  Varicella: chickenpox  Illness may be severe in HIV infection  Visceral dissemination, especially VZV pneumonitis, may occur VZV Disease: Clinical Manifestations (2)

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 7 July 2013www.aidsetc.org Credit: © I-TECH

8 July 2013www.aidsetc.org  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 VZV Disease: Clinical Manifestations (4)

9 July 2013www.aidsetc.org  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 VZV Disease: Clinical Manifestations (5)

10 July 2013www.aidsetc.org  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 VZV Disease: Diagnosis

11 July 2013www.aidsetc.org  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) VZV Disease: Diagnosis (2)

12 July 2013www.aidsetc.org  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 VZV Disease: Preventing Exposure

13 July 2013www.aidsetc.org  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 VZV Disease: Preventing Disease

14 July 2013www.aidsetc.org  Postexposure prophylaxis to prevent primary infection:  Varicella-zoster immune globulin (VariZIG) for VZV- susceptible 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 VZV Disease: Preventing Disease (2)

15 July 2013www.aidsetc.org  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 VZV Disease: Preventing Disease (3)

16 July 2013www.aidsetc.org  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 mg/kg IV Q8H for 7-10 days  May switch to PO treatment as above after fever resolves, if no visceral involvement VZV Disease: Treatment

17 July 2013www.aidsetc.org  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) VZV Disease: Treatment (2)

18 July 2013www.aidsetc.org  Extensive cutaneous lesions or visceral involvement:  Acyclovir mg/kg IV Q8H, until clinical improvement  After clinical improvement and no new cutaneous lesions, switch to PO therapy as above  Duration: 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) VZV Disease: Treatment (3)

19 July 2013www.aidsetc.org  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 VZV Disease: Treatment (4)

20 July 2013www.aidsetc.org  Acute retinal necrosis:  More responsive to antiviral therapy  Acyclovir mg/kg IV Q8H for 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 VZV Disease: Treatment (5)

21 July 2013www.aidsetc.org  Strongly consider ART initiation in patients with multiple recurrences of herpes zoster or a complication of VZV disease VZV Disease: Starting ART

22 July 2013www.aidsetc.org  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 VZV Disease: Monitoring and Adverse Events

23 July 2013www.aidsetc.org  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) VZV Disease: Treatment Failure

24 July 2013www.aidsetc.org  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 VZV Disease: Preventing Recurrence

25 July 2013www.aidsetc.org  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 VZV Disease: Considerations in Pregnancy

26 July 2013www.aidsetc.org  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 VZV Disease: Considerations in Pregnancy (2)

27 July 2013www.aidsetc.org  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 VZV Disease: Considerations in Pregnancy (3)

28 July 2013www.aidsetc.org   Websites to Access the Guidelines

29 July 2013www.aidsetc.org  This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in July 2013 and updated in May  See the AETC NRC website for the most current version of this presentation: About This Slide Set