These guidelines concern the management of anogenital herpes simplex virus infections in adults and give advice on diagnosis, management, and counselling of patients. This guideline replaces the 2007 BASHH herpes guidelines and includes new sections on herpes proctitis, key points to cover with patients regarding transmission and removal of advice on the management of HSV in pregnancy which now has a separate joint BASHH/RCOG guideline.
LangenbergACoreyLAshleyR. A prospective study of new infections with herpes simplex virus type 1 and type 2. N Engl J Med1999; 341: 1432–1438.
2.
ScoularANorrieJGillespieG. Longitudinal study of genital infection by herpes simplex virus type 1 in western Scotland over 15 years. BMJ2002; 324: 1366–1367.
3.
GerettiAM. Genital herpes. Sex Transm Infect2006; 82: iv31–iv34.
4.
BenedettiJCoreyLAshleyR. Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med1994; 121: 847–854.
5.
BenedettiJKZehJCoreyL. Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med1999; 131: 14–20.
6.
WaldAZehJSelkeS. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med2000; 342: 844–850.
7.
KroneMRWaldATabetSR. Herpes simplex virus type 2 shedding in human immunodeficiency virus-negative men who have sex with men: frequency, patterns, and risk factors. Clin Infect Dis2000; 30: 261–267.
8.
SchackerTZehJHuH. Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus–infected men. J Infect Dis1998; 178: 1616–1622.
9.
KlausnerJDKohnRKentC. Etiology of clinical proctitis among men who have sex with men. Clin Infect Dis2004; 38: 300–302.
10.
BissessorMFairleyCKDenhamI. The etiology of infectious proctitis in men who have sex with men differs according to HIV status. Sex Transm Dis2013; 40: 768–770.
11.
GerettiAMBrownDW. National survey of diagnostic services for genital herpes. Sex Transm Infect2005; 81: 316–317.
12.
ScoularA. Using the evidence base on genital herpes: optimising the use of diagnostic tests and information provision. Sex Transm Infect2002; 78: 160–165.
13.
WaldAHuangM-LCarrellD. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis2003; 188: 1345–3151.
14.
WaldAEricssonMKrantzE. Oral shedding of herpes simplex virus type 2. Sex Transm Infect2004; 80: 272–276.
15.
RamaswamyMMcDonaldCSmithM. Diagnosis of genital herpes by real time PCR in routine clinical practice. Sex Transm Infect2004; 80: 406–410.
16.
AshleyRL. Performance and use of HSV type-specific serology test kits. Herpes2002; 9: 38–45.
17.
MorrowRAFriedrichDKrantzE. Performance of the focus and Kalon enzyme-linked immunosorbent assays for antibodies to herpes simplex virus type 2 glycoprotein G in culture-documented cases of genital herpes. J Clin Microbiol2003; 41: 5212–5214.
18.
CopasAJ. An evidence based approach to testing for antibody to herpes simplex virus type 2. Sex Transm Infect2002; 78: 430–434.
19.
WeightmanWTurnerT. Allergic contact dermatitis from lignocaine: report of 29 cases and review of the literature. Contact Dermatitis1998; 39: 265–266.
20.
CoreyLBenedettiJCritchlowC. Treatment of primary first-episode genital herpes simplex virus infections with acyclovir: results of topical, intravenous and oral therapy. J Antimicrob Chemother1983; 12: 79–88.
21.
FifeKHBarbarashRARudolphT. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group. Sex Transm Dis1997; 24: 481–486.
CoreyLMindelAFifeKH. Risk of recurrence after treatment of first-episode genital herpes with intravenous acyclovir. Sex Transm Dis1985; 12: 215–218.
24.
NilsenAAasenTHalsosA. Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet1982; 320: 571–573.
25.
SpruanceSLTyringSKDeGregorioB. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Arch Intern Med1996; 156: 1729–1735.
26.
SacksSLAokiFYDiaz-MitomaF. Patient-initiated, twice-daily oral famciclovir for early recurrent genital herpes: a randomized, double-blind aulticenter trial. JAMA1996; 276: 44–49.
27.
SpruanceSLOverallJCKernER. The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med1977; 297: 69–75.
28.
WaldACarrellDRemingtonM. Two-day regimen of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis2002; 34: 944–948.
29.
AokiFYTyringSDiaz-MitomaF. Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis2006; 42: 8–13.
30.
LeonePATrottierSMillerJM. Valacyclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Clin Infect Dis2002; 34: 958–962.
31.
StrandA. Aborted genital herpes simplex virus lesions: findings from a randomised controlled trial with valaciclovir. Sex Transm Infect2002; 78: 435–439.
32.
PatelRBodsworthNJWoolleyP. Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group. Sex Transm Infect1997; 73: 105–109.
33.
MertzGJLovelessMOLevinMJ. Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women: a multicenter, double-blind, placebo-controlled trial. Arch Intern Med1997; 157: 343–349.
34.
GirardM. Safety of acyclovir in general practice: a review of the literature. Pharmacoepidemiol Drug Saf1996; 5: 325–332.
35.
De Vries HJC, Zingoni A, White JA, et al. 2013 European guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens, http://www.iusti.org/sti-information/pdf/ProctitisGuideline2013.pdf (accessed on 13 November 2014).
36.
WaldALangenbergAGMKrantzE. The relationship between condom use and herpes simplex virus acquisition. Ann Intern Med2005; 143: 707–713.
37.
MartinETKrantzEGottliebSL. A pooled analysis of the effect of condoms in preventing HSV-2 acquisition. Arch Intern Med2009; 169: 1233–1240.
38.
WaldALangenbergAGLinkK. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA2001; 285: 3100–3106.
39.
WaldASelkeSWarrenT. Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding. Sex Transm Dis2006; 33: 529–533.
40.
GuptaRWaldAKrantzE. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. J Infect Dis2004; 190: 1374–1381.
41.
CoreyLWaldAPatelR. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med2004; 350: 11–20.
42.
PertiTBaetenJJohnstonC. High-dose valacyclovir decreases plasma HIV-1 levels more than standard dose acyclovir in HIV-1, HSV-2 positive persons: a randomised, crossover trial. Sex Transm Infect2011; 87: A79–A79.
43.
MuiruABosireRGuthrieB. HSV-2 prevalence and incidence among stable HIV-1 discordant couples in Nairobi, Kenya. Sex Transm Infect2011; 87: A176–A176.
44.
MujugiraAMargaretACelumC. Acyclovir and transmission of HSV-2 from HSV-2/HIV-1 dually infected persons. Sex Transm Infect2011; 87: A185–A185.
45.
WaldAZehJBarnumG. Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir. Ann Intern Med1996; 124: 8–15.
46.
GreenJKocsisA. Psychological factors in recurrent genital herpes. Sex Transm Infect1997; 73: 253–258.
47.
PatelRTyringSStrandA. Impact of suppressive antiviral therapy on the health related quality of life of patients with recurrent genital herpes infection. Sex Transm Infect1999; 75: 398–402.
48.
MertzGJBenedettiJAshleyR. Risk factors for the sexual transmission of genital herpes. Ann Intern Med1992; 116: 197–202.
49.
CarneyORossEIkkosG. The effect of suppressive oral acyclovir on the psychological morbidity associated with recurrent genital herpes. Sex Transm Infect1993; 69: 457–459.
LangenbergABenedettiJJenkinsJ. Development of clinically recognizable genital lesions among women previously identified as having “asymptomatic” herpes simplex virus type 2 infection. Ann Intern Med1989; 110: 882–887.
52.
KesselsRPC. Patients’ memory for medical information. J R Soc Med2003; 96: 219–222.
53.
MertzGJSchmidtOJourdenJL. Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts. Sex Transm Dis1985; 12: 33–39.
54.
WasserheitJN. Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis1992; 19: 61–77.
55.
HookEWCannonRONahmiasAJ. Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals. J Infect Dis1992; 165: 251–255.
56.
MoscaJDBednarikDPRajNB. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci USA1987; 84: 7408–7412.
57.
OstroveJMLeonardJWeckKE. Activation of the human immunodeficiency virus by herpes simplex virus type 1. J Virol1987; 61: 3726–3732.
58.
GoldenMPKimSHammerSM. Activation of human immunodeficiency virus by herpes simplex virus. J Infect Dis1992; 166: 494–499.
59.
MargolisDMRabsonABStrausSE. Transactivation of the HIV-1 LTR by HSV-1 immediate-early genes. Virology1992; 186: 788–791.
60.
KoelleDMAbboHPeckA. Direct recovery of herpes simplex virus (HSV)-specific T lymphocyte clones from recurrent genital HSV-2 lesions. J Infect Dis1994; 169: 956–961.
61.
KreissJCaraëlMMeheusA. Role of sexually transmitted diseases in transmitting human immunodeficiency virus. Genitourin Med1988; 64: 1–2.
62.
KreissJKCoombsRPlummerF. Isolation of human immunodeficiency virus from genital ulcers in Nairobi prostitutes. J Infect Dis1989; 160: 380–384.
63.
SchackerTRyncarzAJGoddardJ. Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1-infected men. JAMA1998; 280: 61–66.
64.
NagotNOuédragoAFoulongneV. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med2007; 356: 790–799.
65.
ToddJGrosskurthHChangaluchaJ. Risk factors influencing HIV infection incidence in a rural African population: a nested case-control study. J Infect Dis2006; 193: 458–466.
66.
FreemanEEWeissHAGlynnJR. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS2006; 20: 73–83.
67.
O’FarrellNToveySJ. High cumulative incidence of genital herpes amongst HIV-1 seropositive heterosexuals in south London. Int J STD AIDS1994; 5: 415–418.
68.
ChenCYBallardRCBeck-SagueCM. Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection. Sex Transm Dis2000; 27: 21–29.
69.
BagdadesEKPillayDSquireSB. Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection. AIDS1992; 6: 1317–1320.
70.
WrightPWHoesleyCJSquiresKE. A prospective study of genital herpes simplex virus type 2 infection in human immunodeficiency virus type 1 (HIV-1)-seropositive women: correlations with CD4 cell count and plasma HIV-1 RNA level. Clin Infect Dis2003; 36: 207–211.
71.
QuinnanGVMasurHRookAH. Herpesvirus Infections in the Acquired Immune Deficiency Syndrome. JAMA1984; 252: 72–77.
72.
MaierJABergmanARossMG. Acquired immunodeficiency syndrome manifested by chronic primary genital herpes. Am J Obstetr Gynecol1986; 155: 756–758.
73.
LeungDTSacksSL. Current recommendations for the treatment of genital herpes. Drugs2000; 60: 1329–1352.
74.
DrewWLBuhlesWErlichKSManagement of herpes virus infection (cytomegalovirus, herpes simplex virus and varicella zoster virus). In: VolberdingPGreeneWJoepL (eds). The medical management of AIDS, 9th ed. London: Saunders, 2012, pp. 433–454.
75.
AokiFY. Management of genital herpes in HIV-infected patients. Herpes2001; 8: 41–45.
76.
FoleyEPatelR. Treatment of genital herpes infections in HIV-infected patients. J HIV ther2004; 9: 14–18.
77.
MarksGLNolanPEErlichKS. Mucocutaneous dissemination of acyclovir-resistant herpes simplex virus in a patient with AIDS. Clin Infect Dis1989; 11: 474–476.
78.
CelumCWaldALingappaJR. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med2010; 362: 427–439.
79.
CelumCWaldAHughesJ. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet2008; 371: 2109–2119.
80.
SacksSLWanklinRJReeceDE. Progressive esophagitis from acyclovir-resistant herpes simplex: clinical roles for DNA polymerase mutants and viral heterogeneity?Ann Intern Med1989; 111: 893–899.
81.
GateleyAGanderRMJohnsonPC. Herpes simplex virus type 2 meningoencephalitis resistant to acyclovir in a patient with AIDS. J Infect Dis1990; 161: 711–715.
82.
EnglundJAZimmermanMESwierkoszEM. Herpes simplex virus resistant to acyclovir: a study in a tertiary care center. Ann Intern Med1990; 112: 416–422.
83.
RatnamIChiuCKandalaN-B. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis2006; 42: 418–427.
84.
FoxPBartonSFrancisN. Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease. HIV Med1999; 1: 10–18.
85.
BodsworthNBlochMMcNultyA. 2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study. Sex Health2008; 5: 219–225.
86.
DeJesusEWaldAWarrenT. Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects. J Infect Dis2003; 188: 1009–1016.
87.
WarrenTHarrisJBrennanCA. Efficacy and safety of valacyclovir for the suppression and episodic treatment of herpes simplex virus in patients with HIV. Clin Infect Dis2004; 39: S258–S266.
88.
DelanySMlabaNClaytonT. Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomized placebo-controlled trial in South Africa. AIDS2009; 23: 461–469.
89.
ReyesM. Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics. Arch Intern Med2003; 163: 76–80.
90.
StránskáRSchuurmanRNienhuisE. Survey of acyclovir-resistant herpes simplex virus in the Netherlands: prevalence and characterization. J Clin Virol2005; 32: 7–18.
91.
HillELHunterGAEllisMN. In vitro and in vivo characterization of herpes simplex virus clinical isolates recovered from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother1991; 35: 2322–2328.
92.
SafrinS. Treatment of acyclovir-resistant herpes simplex virus infections in patients with AIDS. J Acquir Immune Defic Syndr1992; 5: S29–S32.
93.
Gnann J, Davis M, Harden E, et al. Resistance T force on H. acyclovir-resistant HSV from HIV-infected individuals. Population surveillance and in vitro characterization of isolates (abstract). New Orleans, USA, 38th Annual International Disease Society of America (IDSA) Meeting, 2000.
94.
EngelJPEnglundJAFletcherCV. Treatment of resistant herpes simplex virus with continuous-infusion acyclovir. JAMA1990; 263: 1662–1664.
95.
JavalyKWohlfeilerMKalayjianR. Treatment of mucocutaneous herpes simplex virus infections unresponsive to acyclovir with topical foscarnet cream in AIDS patients: a phase I/II study. J Acquir Immune Defic Syndr1999; 21: 301–306.
96.
LalezariJSchackerTFeinbergJ. A randomized, double blind, placebo controlled trial of cidofovir gel for the treatment of acyclovir unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS. J Infect Dis1997; 176: 892–898.
97.
BirchCJTyssenDPTachedjianG. Clinical effects and in vitro studies of trifluorothymidine combined with interferon – for treatment of drug-resistant and -sensitive herpes simplex virus infections. J Infect Dis1992; 166: 108–112.
98.
KesslerHAHurwitzSFarthingC. Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). AIDS Clinical Trials Group. J Acquir Immune Defic Syndr Hum Retrovirol1996; 12: 147–152.
99.
SafrinSCrumpackerCChatisP. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. The N Engl J Med1991; 325: 551–555.
100.
Bestman-SmithJBoivinG. Herpes simplex virus isolates with reduced adefovir susceptibility selected in vivo by foscarnet therapy. J Med Virol2002; 67: 88–91.
101.
LoPrestiAELevineJFMunkGB. Successful treatment of an acyclovir- and foscarnet-resistant herpes simplex virus type 1 lesion with intravenous cidofovir. Clin Infect Dis1998; 26: 512–513.
102.
SnoekR. Antiviral therapy of herpes simplex. Int J Antimicrob Agents2000; 16: 157–159.
Saint-LégerEFilletAMMalvyD. Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet resistant herpes simplex virus infection. Ann Dermatol Venereol2001; 128: 747–749.
105.
KoppTGeusauARiegerA. Successful treatment of an aciclovir-resistant herpes simplex type 2 infection with cidofovir in an AIDS patient. Br J Dermatol2002; 147: 134–138.
106.
British National Formulary, September 2013 – March 2014. BMJ Group and Pharmaceutical Press, London, 2013.
