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1. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and AdolescentsHuman Herpesvirus-8 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

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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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

3. HHV-8 Disease: Epidemiology • Associated with Kaposi sarcoma (KS) (all forms) and certain neoplastic and lymphoproliferative disorders (primary effusion lymphoma [PEL]), multicentric Castleman disease) • HHV-8 seroprevalence in United States: 1-5% • Higher in MSM regardless of HIV serostatus (20-77%) • Higher in some Mediterranean countries (10-20%) and parts of sub-Saharan Africa (30-80%) www.aidsetc.org

4. HHV-8 Disease: Epidemiology (2) • Pathogenesis of HHV-8 disease is unclear • KS and PEL usually seen in advanced immunosuppression (CD4 count <200 cells/µL), but can occur at any CD4 count • KS incidence up to 30% among AIDS patients in United States before use of effective ART • Dramatically lower incidence in recent years • ART prevents and may regress KS lesions • Ganciclovir, foscarnet, and cidofovir given for CMV treatment may prevent or suppress KS • Castleman disease and PEL remain rare www.aidsetc.org

5. HHV-8 Disease: Clinical Manifestations • Most with chronic HHV-8 infection are asymptomatic • Acute infection may cause fever, rash, lymphadenopathy, bone marrow failure, occasional rapid progression to KS • Castleman disease: generalized adenopathy, fever; may progress to multiorgan failure • PEL: pleural, pericardial, or abdominal effusions; mass lesions are less common www.aidsetc.org

6. HHV-8 Disease: Clinical Manifestations (2) • KS presentation varies widely • Most have nontender, purplish, indurated skin lesions • Intraoral lesions are common • Visceral dissemination may occur Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library www.aidsetc.org

7. HHV-8 Disease: Diagnosis • Routine screening for HHV-8 is not indicated • Quantitation of HHV-8 by PCR has no established role in diagnosis • KS: biopsy • Consult with specialist for diagnosis of other suspected HHV-8 disease www.aidsetc.org

8. HHV-8 Disease: Prevention • Preventing Exposure • HHV-8 shedding in saliva and genital secretions may transmit HHV-8 to uninfected partners • Interventions to prevent exposure to HHV-8 not likely to be highly effective, have not been validated; are not recommended • Preventing Disease • Toxicity of anti-HHV-8 therapy outweighs potential benefits • Early initiation of ART likely to be mosteffective prevention measure www.aidsetc.org

9. HHV-8 Disease: Treatment • ART for all: initiate or optimize • Limited studies of HHV-8-specific agents • KS: • Ganciclovir, foscarnet may regress lesions; cidofovir ineffective in 1 study • Chemotherapy if visceral KS; consider if widely disseminated cutaneous KS • Castleman disease: • Preferred: valganciclovir 900 mg PO BID for 3 weeks or ganciclovir 5 mg/kg IV Q12H for 3 weeks or valganciclovir 900 mg PO BID + zidovudine 600 mg PO Q6H for 7-12 days • Alternative: rituximab for 4-8 weeks (effective as alternative or adjunctive therapy; associated with subsequent exacerbation or emergence of KS) • PEL: • Chemotherapy • IV ganciclovir or PO valganciclovir may be useful adjunct • Consult with specialist www.aidsetc.org

10. HHV-8 Disease: Starting ART • Early ART initiation is likely to prevent KS and PEL • ART should be given to all with KS, muticentric Castleman disease, or PEL • Insufficient evidence to support specific ARV regimens www.aidsetc.org

11. HHV-8 Disease:Monitoring and Adverse Events • IRIS reported in HHV-8-infected patients who initiate ART • KS: new onset KS or exacerbations of previously stable disease • Castleman disease: clinical decompensation • PEL: no data • ART is key component of therapy and should not be delayed www.aidsetc.org

12. HHV-8 Disease:Preventing Recurrence • ART recommended for all with HHV-8 disease • May prevent KS progression or recurrence www.aidsetc.org

13. HHV-8 Disease: Considerations in Pregnancy • HHV-8 seropositivity does not appear to affect pregnancy outcome; screening for HHV-8 not indicated • Antiviral therapy for HHV-8 infection during pregnancy is not recommended • Diagnosis as in nonpregnant women • For treatment, consult with specialist • Perinatal transmission occurs infrequently, higher risk with higher maternal antibody titer; may be associated with increased infant mortality www.aidsetc.org

14. Websites to Access the Guidelines • http://www.aidsetc.org • http://aidsinfo.nih.gov www.aidsetc.org

15. About This Slide Set • This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in May 2013 • See the AETC NRC website for the most current version of this presentation: http://www.aidsetc.org www.aidsetc.org