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 Herpes Simplex Virus 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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 Disease  Treatment  Preventing Recurrence  Considerations in Pregnancy Herpes Simplex Virus Disease

4 July 2013www.aidsetc.org  HSV-1: seroprevalence 60% among adults in the United States  HSV-2: seroprevalence 17% among persons aged ≥12 years in United States  95% of HIV-infected persons are seropositive for either HSV-1 or HSV-2  Most infections are not clinically evident  Reactivation occurs intermittently and can result in transmission Herpes Simplex Virus (HSV) Disease: Epidemiology

5 July 2013www.aidsetc.org  HSV-2 increases risk of HIV acquisition 2- to 3-fold  HSV-2 reactivation increases HIV RNA levels in blood and genital secretions of HIV-infected patients HSV Disease: Epidemiology (2)

HSV Disease: Clinical Manifestations  Orolabial herpes: most common in HSV-1 infection  Local sensory prodrome (pain, itching), then papules progressing to vesicles, then ulcers, crusting  Lasts 5-10 days if untreated  Recurs 1-12 times/year; can be triggered by sunlight, stress 6 July 2013www.aidsetc.org Credit: © I-TECH

HSV Disease: Clinical Manifestations (2)  Genital herpes: most common in HSV-2 infection  Prodrome and lesions similar to orolabial lesions  With mucosal disease, dysuria, vaginal or urethral discharge may be present  Perineal disease: may see inguinal lymphadenopathy  Lesions may be mild and atypical  In advanced HIV (CD4 count <100 cells/µL), may see extensive, deep nonhealing ulcerations 7 July 2013www.aidsetc.org Credit: HIV Web Study, © 2006 University of Washington

8 July 2013www.aidsetc.org  Genital HSV-1 episodes indistinguishable from those of genital HSV-2 infection, but HSV-1 recurs less frequently HSV Disease: Clinical Manifestations (3)

9 July 2013www.aidsetc.org  Other manifestations: HSV keratitis, HSV encephalitis, HSV hepatitis, herpetic whitlow are similar in HIV infected and HIV uninfected  HSV retinitis: acute retinal necrosis; can rapidly cause vision loss  Disseminated HSV is rare HSV Disease: Clinical Manifestations (4)

10 July 2013www.aidsetc.org  Mucosal HSV cannot be diagnosed accurately by clinical exam, especially in HIV infection: laboratory diagnosis should be pursued  Swab base of fresh vesicle:  Viral culture  HSV DNA PCR (most sensitive; not widely available)  HSV antigen detection  If HSV detected, obtain type (genital HSV-1 recurs less frequently) HSV Disease: Diagnosis

11 July 2013www.aidsetc.org  Type-specific serologic assays: can use in asymptomatic persons, or with atypical lesions  Consider routine serologic testing for HSV-2 in all HIV- infected patients  If infected with HSV-2: counsel about risk of transmission to sex partners, means of preventing transmission HSV Disease: Diagnosis (2)

12 July 2013www.aidsetc.org  Most HIV-infected persons have HSV-1 and HSV-2  If HSV-2 seronegative  Test partners for HSV-2 before initiating sexual activity  Latex barriers reduce HSV-2 acquisition (at least in heterosexual couples)  Avoid sexual contact with partners who have evident herpetic lesions  Sexual transmission of HSV-2 usually occurs during asymptomatic shedding  Antiviral therapy (valacyclovir) can reduce HSV-2 transmission (not studied in HIV infection) HSV Disease: Preventing Exposure

13 July 2013www.aidsetc.org  Antiviral prophylaxis to prevent primary HSV is not recommended  Antiviral prophylaxis after exposure has not been studied HSV Disease: Preventing Disease

14 July 2013www.aidsetc.org  Can treat episodically when lesions occur or with daily therapy to prevent recurrences; consider:  Frequency and severity of recurrences  Risk of HSV-2 transmission  Potential for adverse HSV-2 effect on HIV viral loads in plasma and genital secretions  Treatment of individual episodes does not reduce risk of HSV-2 transmission to sex partners HSV Disease: Treatment

15 July 2013www.aidsetc.org  Orolabial HSV and genital HSV (initial or recurrent)  Valacyclovir 1 g PO BID, famciclovir 500 mg PO BID, or acyclovir 400 mg PO TID  Duration: 5-10 days (orolabial); 5-14 days (genital)  Severe mucocutaneous HSV  Acyclovir 5 mg/kg IV Q8H until lesions begin to regress, then PO therapy as above, until lesions have completely healed HSV Disease: Treatment (2)

16 July 2013www.aidsetc.org  Orolabial HSV usually should not influence decision about when to start ART  Prompt initiation of ART: chronic cutaneous or mucosal HSV refractory to treatment, visceral or disseminated HSV  ART with immune reconstitution may improve frequency and severity of genital HSV episodes  ART does not reduce frequency of genital HSV shedding HSV Disease: Starting ART

17 July 2013www.aidsetc.org  No laboratory monitoring needed unless advanced renal impairment  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 dosages used for HSV treatment  Atypical lesions reported in persons initiating ART HSV Disease: Monitoring and Adverse Events

18 July 2013www.aidsetc.org  Lesions should begin to resolve within 7-10 days of therapy initiation  Suspect drug resistance if no improvement  Culture lesion, perform susceptibility testing HSV Disease: Treatment Failure

19 July 2013www.aidsetc.org  Acyclovir-resistant HSV  Preferred:  Foscarnet mg/kg/day IV in 2-3 divided doses until clinical response  Alternatives (21-28 days or longer):  Topical trifluridine, topical cidofovir, or topical imiquimod for external lesions  IV cidofovir HSV Disease: Treatment Failure (2)

20 July 2013www.aidsetc.org  Suppressive therapy recommended for patients with frequent or severe recurrences; consider for all with HSV-2  Valacyclovir 500 mg PO BID  Famciclovir 500 mg PO BID  Acyclovir 400 mg PO BID  Daily HSV suppressive therapy causes decrease in HIV RNA in plasma and anal and genital secretions, and lower risk of HIV progression  Suppressive HSV therapy does not decrease risk of HIV transmission  Suppressive therapy is continued indefinitely, regardless of CD4 cell count improvement HSV Disease: Preventing Recurrence

21 July 2013www.aidsetc.org  Diagnosis of mucocutaneous HSV as in nonpregnant adults  Visceral disease more likely during pregnancy  May be transmitted to fetus or neonate  Risk of neonatal HSV greatest if mother has primary HSV infection during late pregnancy  In utero transmission rare, but severe cutaneous, ocular, and CNS damage  Most neonatal infection occurs via exposure to maternal genital fluids during birth HSV Disease: Considerations in Pregnancy

22 July 2013www.aidsetc.org  Cesarean delivery lowers risk of transmission; recommended for women with prodrome or visible HSV genital lesions at onset of labor  Acyclovir or valacyclovir during late pregnancy suppresses genital HSV outbreaks and shedding in HIV- uninfected women; reduces need for cesarean delivery; likely to have similar efficacy in HIV-infected women  Efficacy in reducing incidence of neonatal herpes is unknown HSV Disease: Considerations in Pregnancy (2)

23 July 2013www.aidsetc.org  Treatment  Acyclovir: most experience in pregnancy  Valacyclovir, famciclovir: appear to be safe and well tolerated during pregnancy  Suppressive therapy:  Valacyclovir or acyclovir recommended starting at 36 weeks, for pregnant women with recurrences of genital HSV during pregnancy HSV Disease: Considerations in Pregnancy (3)

24 July 2013www.aidsetc.org  Maternal genital HSV increases risk of perinatal HIV transmission in women not on ART; unknown effect for women on ART  Whether HSV suppression reduces risk of HIV transmission during pregnancy, birth, or breast-feeding is unknown HSV Disease: Considerations in Pregnancy (4)

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

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