Emily J. Erbelding, M.D., M.P.H. and Khalil G. Ghanem, M.D.
- Due to synergy between HSV and HIV transmission, pts with HSV should be tested for HIV and pts with HIV should be evaluated for clinical evidence of HSV.
- High seroprevalence rates in sub-Saharan Africa (30-80%). HIV+ pts have consistently higher HSV-2 prevalence than HIV-negative pts.
- Recent double-blind RCT in Tanzania found acyclovir suppressive therapy for HSV-2+/HIV- women did not reduce incidence of HIV infection.
- Dx of HSV lesions is clinical in Zambia as Cx, Bx, PCR, DFA, serology or Tzanck prep rarely performed.
- Treatment in Zambia (per National Guidelines 2007 on HIV Management) are same as below with acyclovir; other antivirals (valacyclovir, famciclovir, foscarnet) not generally available in Zambia.
Zambia Information Author: David Riedel, M.D.
- Herpes simplex virus-1 (HSV-1)
- Herpes simplex virus-2 (HSV-2)
- HSV-1 and HSV-2 are double-stranded enveloped DNA viruses.
- Chronic herpesvirus infection, establishes latency in sensory ganglia of nerves innervating site of initial mucocutaneous infection.
- Prevalence of both HSV-1 or -2 infection up to 80% in clinical series of HIV+ persons.
- Activates HIV replication and enhances sexual transmission of HIV.
- HSV-1: orolabial ulcers, herpetic whitlow (felon), stomatitis, keratitis, anogenital ulcerations, proctitis, esophagitis, tracheobronchitis/pneumonitis, retinal necrosis, encephalitis, transverse myelitis, disseminated infection.
- HSV-2: ulcerative anogenital disease and proctitis more common than with HSV-1, though clinical syndromes overlap extensively; meningitis, lumbosacral radiculitis.
- Genital herpes: classic presentation is grouped vesicles on erythematous base; "atypical" presentations (erythema, itching, tingling, shallow or linear erosions) are also common in both immunocompetent and in HIV+ hosts.
- DDx of genital ulcers: syphilis, chancroid, Behcet's disease, herpes zoster, lymphogranuloma venereum, granuloma inguinale, leishmaniasis, blastomycosis, mucocutaneous manifestation of inflammatory bowel disease, idiopathic ulcers.
- DDx of orolabial ulcers: aphthous ulcers, Behcet's disease, histoplasmosis.
- DDx of perianal herpes/ proctitis: similar to genital ulcer disease; also consider HPV-associated anal lesions; gonorrhea and chlamydia.
- More severe visceral disease (esophagitis, retinal necrosis) can be a complication of AIDS; other manifestations (pneumonitis, encephalitis, other dissemination) also describe in case reports or small clinical series.
- Cx from lesion confirms Dx; sensitivity of vesicular fluid highest, especially with primary episode; lower yield with recurrence, if lesions in healing phase, or if antiviral therapy initiated.
- "Tzanck prep" of lesion scrapings may demonstrate multinucleated giant cells (60% sensitive for infection with Herpesviridae family), not specific for HSV
- PCR more sensitive than Cx; can discriminate HSV-1/2; "gold standard" in diagnosing HSV encephalitis.
- Skin Bx: may be useful with atypical lesions; antigen detection by HSV-1/2 DFA staining diagnostic.
- Chronic infection diagnosed by type-specific serologic testing, but not likely to be useful in diagnosing specific etiology of ulcerative lesions.
- HIV+ pts with relatively preserved immune function may be managed similarly to HIV-negative pts; those with low CD4 may benefit from higher dose of antivirals and/or longer duration of therapy.
- Extend duration of therapy for all clinical episodes if lesion healing incomplete after the term stated; consider possibility of drug resistance.
- Bacterial superinfection may complicate genital outbreaks causing perineal cellulitis, requiring antibacterial as well as more aggressive antiviral therapy.
- Higher rates of subclinical HSV shedding in immunosuppressed HIV+ persons (compared to HIV-).
- Goal of therapy and common endpoints in clinical efficacy trials include Sx resolution, lesion healing, and preventing new lesion occurrence. Pt and provider may elect to not treat mildly symptomatic herpes, especially in HIV+ with normal CD4.
- Recent RCTs using acyclovir in HIV-/ HSV+ patients did not decrease risk of HIV acquisition; results of a study using acyclovir to decrease HIV transmission in HSV+/HIV+ patients are anticipated.
Acyclovir 400 mg PO three times a day x 7-10 d, OR 200 mg PO 5x/d x 7-10 d.
- Valacyclovir 1 gm PO twice-daily x 7-10 d.
- Famciclovir 250 mg PO three times a day x 7-10 d.
Acyclovir 400 mg PO three times a day x 5d.
- Valacyclovir 1 gm PO twice-daily x 5-10 d.
- Famciclovir 500 mg twice-daily x 5-10d.
- Orolabial herpes: penciclovir 1% cream to lesions q2h while awake x 4d (not evaluated in HIV+ pts.)
- Orolabial herpes: valacyclovir 2 gm q12h x 2 doses (not evaluated in HIV+ pts.)
Acyclovir 5-10 mg/kg IV q8hr (preferred for severe or progressive disease), continue until clinical improvement observed.
- Valacyclovir 1 gm PO three times a day may be useful for mucocutaneous disease of less clinical severity.
- Thymidine kinase-deficient mutations most frequent cause of acyclovir resistance; cross-resistant to valacyclovir and famciclovir. May be preventable in immunosuppressed patients by initial use of higher dose ACV (or valacyclovir, famciclovir).
- Foscarnet 40 mg/kg IV q8h.
- Cidofovir 1-3% cream applied daily has had reported success in case reports for acyclovir resistance in refractory mucocutaneous lesions.
- Consider viral resistance testing when clinically significant disease progresses or persists despite therapy.
Acyclovir 3% ophth ointment 5 x/d x 7-14 d.
- Addition of systemic antiviral therapy indicated if more extensive or complicated ocular disease.
Acyclovir 400 mg PO twice-daily or three times a day.
- Valcyclovir 500 mg PO twice-daily.
- Famiciclovir 500 mg PO twice-daily.
- Suppressive therapy clinically indicated if herpes outbreaks frequent or severe.
- Some experts recommend type-specific serologic testing in HIV+ pts with chronic suppressive antiviral therapy based on results: not currently standard of care.
| Acyclovir ||Less convenient due to higher dosing frequency than oral alternatives.
| Cidofovir ||Topical preparation not commercially available; drug + vehicle must be prepared by pharmacist.
| Famciclovir ||Orally bioavailable prodrug of penciclovir and more convenient dosing than acyclovir; not useful if ACV-resistant.
| Foscarnet ||For ACV-resistant HSV: 40 mg/kg IV q8h; rare cases of foscarnet -resistant HSV in immunocompromised hosts have been reported.
| Penciclovir ||Active product of famciclovir; topical application of 1% cream more effective than placebo in treating herpes labialis of lips and face, but use not endorsed in genital herpes, on mucous membranes, or in immunocompromised hosts.
| Valacyclovir ||Better absorption, more convenient dosing than acyclovir; not useful if acyclovir-resistant.
- Centers for Disease Control and Prevention ;
Sexually transmitted diseases treatment guidelines 2006. Centers for Disease Control and Prevention.;
MMWR Recomm Rep;
55-11 ; pp.
Basis for recommendation
Comments:Consensus panel guidelines on approach to HSV diagnosis and management.