Presentation on theme: "Gary A. Richwald, MD, MPH Clinical Virologist"— Presentation transcript:
1Genital Herpes: Clinical Update on Testing, Treatment and the Prevention of Transmission Gary A. Richwald, MD, MPHClinical VirologistFormer Director and Chief PhysicianLos Angeles County Sexually Transmitted Disease ProgramConsultant, American Social Health AssociationMedical Advisor – LA/Orange County HELP Groups
2The Herpesvirus Family AlphaherpesvirusesHerpes simplex virus type 1 (HSV-1)Herpes simplex virus type 2 (HSV-2)Varicella-zoster virus (VZV)BetaherpesvirusesCytomegalovirus (CMV)Human herpesvirus 6 (HHV-6)Human herpesvirus 7 (HHV-7)GammaherpesvirusesEpstein-Barr virus (EBV)Human herpesvirus 8 (HHV-8)The family of herpesviruses that infects humans is divided into 3 subfamilies, based on biologic differences: alphaherpesviruses, betaherpesviruses, and gammaherpesviruses.Alphaherpesviruses are characterized by a short reproductive cycle, rapid spread in culture, efficient destruction of infected cells, and capacity to establish latent infections primarily, but not exclusively, in sensory ganglia. This subfamily includes the herpes simplex viruses (HSV-1, HSV-2) and the varicella-zoster virus (VZV).Betaherpesvirsuses exhibit a long reproductive cycle, and infection progresses slowly in culture. Infected cells frequently become enlarged, and the virus can be maintained in latent form in secretory glands, lymphoreticular cells, kidneys, and other tissues. This subfamily includes cytomegalovirus (CMV) and roseola (HHV-6).Gammaherpesviruses are usually specific for either T or B lymphocytes. Latent virus is frequently demonstrated in lymphoid tissue. This subfamily includes mononucleosis (EBV) and Kaposi’s sarcoma-associated herpesvirus (HHV-8).References:Corey L. Herpes simplex virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000:Pertel PE, Spear PG. Biology of herpesviruses. In: Holmes KK, Mardh P, Sparling PF, et al, eds. Sexually Transmitted Diseases. 3rd ed. New York, NY: McGraw-Hill Book Co; 1999:
3The HerpesvirusesThe herpesviruses are a group of related, medium- to large-sized DNA viruses belonging to the family Herpesviridae. Approximately 100 herpesviruses have been identified, of which at least 8 infect humans.Shown in this slide is an electron micrograph of a herpesvirus.In the center of the virion is a double-stranded DNA containing 125,000 to 250,000 base pairs.This DNA is surrounded by an icosahedron-shaped protein-protective layer, known as the capsid, approximately 125 nM in diameter.An amorphous layer of viral proteins, called the tegument, surrounds the capsid, which is further enclosed by a lipid bilayer envelope derived from the host cell and contains glycoprotein spikes.Reference:Pertel PE, Spear PG. Biology of herpesviruses. In: Holmes KK, Mardh P, Sparling PF, et al, eds. Sexually Transmitted Diseases. 3rd ed. New York, NY: McGraw-Hill Book Co; 1999:
4Genital Herpes is the Most Prevalent STI Chlamydia2 millionHepatitis B417,000HPV20 millionHIV560,000Genital Herpes (HSV-2)45 millionHerpes is the Most Prevalent STDGenital herpes (HSV-2) is one of the most common sexually transmitted diseases (STD) in the United States, with as many as one million people in the US becoming infected each year1-4It is estimated that 1 in 5 Americans over the age of 14 (45 million) are infected with genital herpes1,4Genital herpes is twice as prevalent as HPVIn terms of annual incidence, herpes is the 4th most common STD after HPV (5.5 million), trichomoniasis (5.0 million), and chlamydia (3 million)1 million new cases of genital herpes per year are occurring in the United States3Although genital herpes (GH) is one of the most common STDs, many primary care physicians believe it is virtually nonexistent in their patient population1 Million New Genital Herpes (GH) Infections per Year in the USHenry J. Kaiser Family Foundation.CDC Web site. Tracking the hidden epidemics: trends in STDs in the United States 2000:1-31.Xu, F. CDC. NHANES , Oral Presentation. IDSA, Boston 2004.References:1. Data on file, GlaxoSmithKline.2. The Henry J. Kaiser Family Foundation Web site. Sexually transmitted diseases in America: how many cases and at what cost? December Available at Accessed October 13, 2004.3. Centers for Disease Control and Prevention Web site. Tracking the hidden epidemics 2000: trends in STDs in the United States. Available at Accessed February 10, 2003.4. Xu, F. CDC. NHANES , Oral Presentation. IDSA, Boston 2004.
5Suburban Seroprevalence of HSV-2 Study Design: six US communities, six private medical practices in each community: Atlanta, Baltimore, Boston, Chicago, Dallas, and DenverBackground: Many primary care providers believe genital herpes is not seen in their patient populationObjective: Determine seroprevalence of HSV-2 in suburban practices150 patients per practice, equal number of men and womenParticipation occurred as part of normal visit to office75% Caucasian, 14% African-American, 4% Hispanic45% household income >$60,000/year, 35% college gradParticipation level very highSignificance of HSV-2 Seroprevalence FindingsThe significance of the study findings include two very important points:First, only 4.3% of the study population reported a history of genital herpes versus a type-specific serology testing prevalence rate of 25.5%; one fourth of all patients age 18-59!Second, of the 25.5% that tested positive for HSV-2, less than 12% of them reported knowing that they had genital herpes or were HSV-2 positiveTherefore, the population of sexually active individuals infected with HSV-2, for the most part does not know they are infected and are at the risk of transmitting the virus to their sexual partnersLeone P. Sex Transm Dis 2004;31(5):References:1. Data on file. GlaxoSmithKline.2. Fleming DT, Leone P, Lei L, Deeter RG, Gilsenan AW, Justus SE. Seroprevalence of HSV-2 in suburban primary care offices. Presented at: International Society for Sexually Transmitted Disease Research. July 28, Ottawa, Canada.
6Suburban Seroprevalence of HSV-2 Less than 5% of year old patientsreport being told they have genital herpesPatients (%)Known History of HSV-2 Seroprevalence RatesAll study participants were asked the following question: “Have you ever been told by a healthcare provider that you have genital herpes?”Of the 5,433 respondents to this question, 4.3% indicated they have been told that they have genital herpes4.3%N=5,433Patients acknowledgethey have GHLeone P. Sex Transm Dis 2004;31(5):Reference:Data on file, GlaxoSmithKline.
788% did NOT know they had GH Suburban Seroprevalence of HSV-2 9 Out of 10 Did Not Know They Had Genital Herpes12% reported having GHPatients (%)N=5,452Patients seropositive for HSV-20%10%20%30%40%25.5%9 Out of 10 Did Not Know They Had GHIn the Suburban Office Prevalence Study, of those who were seropositive, 88% did NOT know they had genital herpes. This is consistent with previous studies.Additional Findings96% of people wanted to know if they are infected with HSV-2Most parameters did not impact the likelihood of being seropositive for HSV-2, however, a few parameters did have some impact on seroprevalence rates:Gender females were at greater risk than males, 28.3% and 22.0%, respectivelyAge bracket years were at greater risk than participants years oldAfrican-American raceLess than a post graduate educationHigher number of lifetime sexual partnersParameters of geographic region when adjusted for race/ethnicity, employment, income, and marital status had no effect on prevalence rates88% did NOT know they had GHLeone P. Sex Transm Dis. 2004;31(5):Reference:Leone P, Fleming DT, Gilsenan A, Li L, Justus S. Seroprevalence of Herpes Simplex Virus-2 in Suburban Primary Care Offices in the United States. Sexually Transmitted Diseases. May 2004; 31(5):Data on file, GlaxoSmithKline.
8The Significance of Genital Herpes May cause physical and psychological concerns (1)HSV-2 infection increases the risk of HIV-1 infection byat least 2-fold, possibly as much as 4-fold (2)Impact on social health89% expressed concern and anxiety about transmitting to a partner (3)Transmission of herpes to newborn during pregnancy or deliveryoccurs in 1 per 3,200 live births (4)may lead to serious complications such as seizures, blindness, psychomotor retardation, spasticity, learning disabilities, and death2The Significance of Genital HerpesThe diagnosis of HSV-2 infection may cause may cause physical and psychological concerns1In addition, HSV-2 infection Increases the risk of acquiring a HIV-1 infection by 2-fold2Genital herpes impacts social health, and 89% of patients have expressed concern over transmitting the virus to their sexual partners3Transmission of herpes to newborn during delivery can lead to serious complications in 1 per 3,200 live births4Serious complications include seizures, blindness, psychomotor retardation, spasticity, learning disabilities, and death1. CDC Sexually Transmitted Diseases Guidelines2. Wald A, Link K. J Infect Dis. 2002;185:45-52.3. Catotti DN et al. Sex Transm Dis. 1993;20:77-80.4. Brown Z et al. JAMA. 2003;289:References:1. Centers for Disease Control and Prevention. Sexually transmitted diseases guidelines MMWR Morb Mortal Wkly Rep. 2002;51(RR-6):16.2. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2 seropositive persons: a meta-analysis. J Infect Dis. 2002;185:45-52.3. Catotti DN, Clarke P, Catoe KE. Herpes revisited: still a cause for concern. Sex Transm Dis. 1993;20:77-80.4. Brown Z, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA. 2003;289:
9Herpes Simplex Virus 1 and 2 HSV-2- Almost entirely genital; oral infections rare- >95 % of recurrent genital herpes- More frequent asymptomatic shedding than HSV-1- Very low, if any, risk of HSV-1 acquisitionHSV-1- Mostly orolabial (cold sores, fever blisters)- Increasing proportion of cases of primary genital herpes,especially in younger sexually active patients- Shorter initial and recurrent outbreaks than HSV-2- Infrequent recurrences and asymptomatic shedding- Continued risk for HSV-2 acquisitionDifferences in HSV-1 and HSV-2 Genital InfectionIt is important to know HSV type because HSV-1 and HSV-2 differ in their natural history and prognosis. HSV-2 is associated with more frequent recurrent episodes and a higher rate of asymptomatic viral shedding.These differences lead to different management strategies for these infections. In addition, persons with genital HSV-1 remain susceptible.
10Type-Specific Methods for Diagnosing Genital Herpes Swab symptomatic area to detect virusCulturePolymerase Chain Reaction (PCR)Draw blood to look for type-specific antibodiesThere are Several Type Specific Methods for Diagnosing Genital HerpesThere are 3 main methods to confirm a genital herpes diagnosis.Swab symptomatic area to detect virusCulturePolymerase Chain Reaction (PCR)Request typing for samples analyzed via culture or PCRBlood draw to detect antibodies using approved IgG type specific serology tests:Western Blot: The gold standardHerpeSelect® IgG ELISA HSV-1 or -2HerpeSelect® IgG Immunoblot HSV-1 and -2biokitHSV-2 Rapid TestCaptia HSV-2 Select Test™HerpeSelect is a registered trademark of Focus Diagnostics, Inc. GSK has no financial interest in Focus Diagnostics.biokitHSV-2 Rapid Test is owned by biokit. GSK has no financial interest in biokit.Captia is a trademark of Trinity Biotech. GSK has no financial interest in Trinity.
11Detection of Virus Using a Swab of Lesion/Infected Area Culture: if results are non type-specific, request lab to perform typingNot useful during intra-lesional periodIf Positive:Patient likely has GH; false positives are very rareIf Negative:No detectable virus in that sample; does NOT mean patient doesn’t have GHFalse negatives are very common, low sensitivity – often <50% for primary herpes, <30 % for recurrent herpes, especially when collected after day 3 of outbreak when viral load is lowThere are two methods of detecting virus using a swab – culture and PCR.CULTUREViral culture is the gold standard for diagnosing genital herpes. If the culture is positive, patient likely has GH; false positives rareHowever if the result is negative, it does NOT mean patient doesn’t have GH – it just means there was no virus in that sample.False negatives are common.Up to 76% false negative rate compared to PCRPCRThe second method to detect virus is using PCR – polymerase chain reaction. PCR is a more sensitive test – it is 3-4 times more sensitive than culture in detecting virus. PCR is a DNA amplification test. It is not widely commercially available and special care is required for transport.If the PCR is positive, patient likely has GH; false positives rareFalse negatives are rareIf the result is negative, it does NOT mean patient doesn’t have GH – it just means there was no virus in that sampleReferences:Ashley R. Herpes simplex viruses: types 1 and 2. In: Lennette E, ed. Laboratory Diagnosis of Viral Infections. 3rd ed. New York, NY: Marcel Dekker; 1999:Gupta R, Wald A, Krantz E, et al. Valacyclovir and Acyclovir for Suppression of Shedding of Herpes Simplex Virus in the Genital Tract. J Infect Dis. 2004; 190 (15):Wald A, Corey L, Cone R, Hobson A, Davis G, Zeh J. Frequent Genital Herpes Simplex Virus 2 Shedding in Immunocompetent Women J Clin Inv. 1997;99(5):Wald A, Link K. Risk of Human Immunodeficiency Virus Infection in Herpes Simplex Virus Type-2 Seropositive Persons: A Meta Analysis. J Infect Dis. 2003;188:
12Detection of Virus Using a Swab of Lesion/Infected Area PCR (Polymerase Chain Reaction): 3-4 times more sensitive than culture, most often not available outside of hospital and can be very expensive (5- 15 times the cost of culture)If Positive:Patient likely has GH; false positives are very rareIf Negative:False negatives are rareNo virus in sample taken; patient could still have GHAshley R. Laboratory Diagnosis of Viral Infections. 1999:Gupta R, et al. J Infect Dis. 2004; 190 (15):Wald A. J Clin Inv. 1997; 99(5):Wald A. J Infect Dis. 2003;188:
13Detection of HSV-2 Antibody Using Type-Specific Serology Principal test:FDA-approved IgG type-specific antibody tests• HerpeSelect® ELISA HSV-2 or HSV-1HerpeSelect® Immunoblot for HSV-2 and HSV-1biokit HSV-2 Rapid TestMuch less commonly used TSST:Western blotFirst type-specific test, not FDA approvedNot commercially available but can be sent to Univ. of WashingtonDetection of HSV-2 Antibody Using Type Specific SerologyWhen no lesion is available to culture or the lesion has started healing, consider type specific serology. There are several accurate type specific serology tests available.Western Blot is the gold standard test for HSV-2, developed by Dr. Rhoda Ashley Morrow at the University of Washington. It is not commercially available, however the lab does accept shipments from offices. Call for information. Cost to the patient is approx. $ Results are available in 4-6 days.There are FDA Approved IgG type specific serology tests available. There are also many non-type specific tests on the market so it’s important to know which test your lab runs.The sensitivity and specificity for the HSV-2 tests are listed below:*Sensitivity SpecificityWestern Blot HSVHerpeSelect ELISAHerpeSelect Immunoblot HSVbiokitHSV-2 onlyCaptia HSV-2 Select Test not available at press time* Test results should be correlated to clinical history and epidemiologic data, as the likelihood of a false-positive result increases with decreasing underlying prevalence of HSV-2.GSK does not warrant the accuracy of any diagnostic tests. Please consult the manufacturers for further information about these products.HerpeSelect is a registered trademark of Focus Diagnostics, Inc. GSK has no financial interest in Focus Diagnostics.biokitHSV-2 Rapid Test is owned by biokit. GSK has no financial interest in biokit.Captia is a trademark of Trinity Biotech. GSK has no financial interest in Trinity.References:1. HerpeSelect Product Information. Focus Diagnostics, Oct. 15, 2004.2. biokit Package Insert. July 16, 2004.
14HerpeSelect-2 and HerpeSelect-1 Type-Specific Tests
15Genital Herpes: FDA-Approved Type-Specific Serologic Tests Sensitivity* Specificity* (%) (%)`Type of TestHerpeSelectTM 2 ELISA IgG HerpeSelectTM 1 ELISA IgGHerpeSelectTMImmunoblot 2Immunoblot 1Accurate type-specific serologic assays allow identification of silent carriers of HSV-2 infection among patients with or without preexisting antibodies to HSV-1.These tests can provide useful information in symptomatic patients when antigen or culture tests are not helpful.The newer commercial tests provide rapid serologic test results with high sensitivity and high specificity (range 93%-98%).Only one point-of-care serologic test is currently available. The POCkit® HSV-2 Rapid Test by Diagnology (Belfast, Northern Ireland) provides rapid, office-based, type-specific diagnosis of HSV-2 infection.Antibody tests become positive as early as three weeks, and by 16 weeks almost all tests of those infected are positive*Based on comparison with the results of Western blot test. Percentages given for HerpeSelect, and Immunoblot, are for HSV-2 antibodiesHerpeSelectTM is a trademark of Focus DiagnosticsAdapted from Ashley RL. Sex Transm Infect. 2001;77:Ashley-Morrow R et al. Am J Clin Pathol; 2003;120Reference:Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect. 2001;77:
16Test Order Codes for HerpeSelect® 1 and 2 IgG Type-Specific Antibodies Quest DiagnosticsRuns only HerpeSelect IgG serologyHSV-2 alone, HSV-1 alone, or the combinationOrder codes:HerpeSelect HSV-1 ELISA: XHerpeSelect HSV-2 ELISA: XHSV-1 and HSV-2 combined: XLabcorpRuns non-specific as well as type-specific HerpeSelect testsHerpeSelect HSV-1 ELISA:HerpeSelect HSV-2 ELISA:HSV-1 and HSV-2 combined:Mayo Clinic∙ Runs only HerpeSelect IgG serology∙ Order codes: requires ordering both tests together- HerpeSelect HSV-1 and HSV-2 ELISA: 84429Test Order Codes for the HerpeSelect® ELISA HSV-2 and HSV-1 at Two Major LabsTwo of the largest labs run HerpeSelectQuest Diagnosticsruns only HerpeSelectHSV-2 alone, HSV-1 alone, or the combinationOrder codes for majority of Quest sites:HerpeSelect HSV-2 ELISA: 3640HerpeSelect HSV-1 ELISA: 3636HSV-1 and HSV-2 together: 6447Codes vary by facility; confirm code with lab before orderingLabCorpfirst performs HSV test that is not type specificif sample tests HSV+, run HerpeSelect HSV-2 type-specific testPossible order codes: or
17Is IgM Useful in Distinguishing New vs. Recurrent GH Infection? No! Do not order IgM antibodies to diagnose new vs.recurrent GH infection. Often laboratories automatically do IgM testWhy aren’t IgM tests helpful in determining the recency ofGH infection?- IgM tests are not type-specific – IgM could be from HSV-1or HSV-2!- Each of the many episodes of viral reactivation canproduce new IgM and IgG, making it difficult to interpretresults as to acuity of infection. For example, some firstinfections can have no IgM (only IgG) and some recurrentinfections can have IgM.Is IgM Useful in Distinguishing Initial Episodes from Recurrent Infection?IgM is another type of serology test that can be ordered.Commercially available IgM tests are not useful in diagnosing genital herpesCannot distinguish primary from recurrent infectionDoes not distinguish type 1 from type 2In a study by Ashley and colleagues, there were two key findings:65% of patients with recurrent herpes episodes had only IgG, while 35% had both IgM and IgG to gG-2.18% of patients with primary infection had both IgM and IgG.The results show that first-episode infection cannot be distinguished from recurrent episodes by testing with IgM.Ashley RL. Herpes 1998;5:33–38.ReferenceAshley RL. Type-specific antibodies to HSV-1 and 2: review of methodology. Herpes 1998;5:33–38.
18Who Is a Candidate for HSV Serologic Testing? Patient with typical GH lesion; culture not done or negativePatient with recurrent clinical symptoms suggestive of GH, but without typical GH lesionsSexual partners of patients with GHPatient request to know infection statusSTD screeningPrenatal screeningPatient with HIV infectionA major advance in the diagnosis of genital herpes is the development of type-specific serologic tests for HSV that are commercially available.Candidates for serologic testing can be grouped into 4 categories:Someone who has had a partner in the past and wants to know whether they have become infectedSomeone who has suspicious symptomsSomeone who has been diagnosed by visual inspection and doesn’t believe itAnyone getting an STD screenParents of babies with neonatal herpes.Reference:Diagnosing genital herpes. Diagnology. Available at Accessed March 16, 2001.
19Who Is a Candidate for HSV Serologic Testing Who Is a Candidate for HSV Serologic Testing? Persons with clinical evidence of HSVPatient has typical GH lesion; culture/PCR not done or negativePatient originally diagnosed with HSV by clinical exam only without culture/PCRPatient has recurrent clinical symptoms of lower genital tract inflammation not explained by another diagnosis (patient does not have typical GH lesions)Note: Helpful in making definitive diagnosis, eliminating misdiagnoses, differentiating between genital HSV-2 and HSV-1 which have different prognoses.A major advance in the diagnosis of genital herpes is the development of type-specific serologic tests for HSV that are commercially available.Candidates for serologic testing can be grouped into 4 categories:Someone who has had a partner in the past and wants to know whether they have become infectedSomeone who has suspicious symptomsSomeone who has been diagnosed by visual inspection and doesn’t believe itAnyone getting an STD screenParents of babies with neonatal herpes.Reference:Diagnosing genital herpes. Diagnology. Available at Accessed March 16, 2001.
20Who Is a Candidate for HSV Serologic Testing Who Is a Candidate for HSV Serologic Testing? Testing driven by patient risk-profile or requestPatient with a previous or a current partner with GHPatient needs STD screening due to risk statusPatient requests STD screeningPatient requests HSV testingPatient is being evaluated for sexual assaultNote: For patients in a relationship, HSV status will help determine if the patient or partner(s) would benefit from suppressive therapy to reduce transmission to uninfected partner(s).
21Who Is a Candidate for HSV Serologic Testing? Special populations Pregnant womenPatients prior to transplant or starting immunosuppressive therapyPatients with HIV infectionPatients at risk for sexual acquisition of HIV infectionNote: HSV-2 infected pregnant women should be offered a month of suppressive therapy prior to delivery. HSV-2 increases the risk of HIV transmission and HIV acquisition and can accelerate HIV progression.
22Asymptomatic Viral Shedding Asymptomatic viral shedding is the presence of HSV on the surface of the skin/mucosa in the absence of signs and symptomsSubclinical shedding may occur in the presence of symptoms such as itching or tingling without any apparent lesionsThe majority of people with genital HSV-2 shed virus asymptomatically; frequency of shedding is highestin first few years after acquisitionPossible HSV-2 shedding sites can be described to patients as the area covered by “boxer shorts”Asymptomatic Viral Shedding (AVS)Many clinicians have observed and are familiar with herpetic lesions. Many also know that the virus can be more readily transmitted to another individual while a patient has an active lesionHowever, the virus can also be transmitted when a patient has virus present on the skin without lesions or symptomsAsymptomatic viral shedding is the presence of HSV on the surface of the skin/mucosa in the absence of signs and symptomsSubclinical shedding may occur in the presence of symptoms such as itching or tingling without any apparent lesionsMany clinicians use these terms interchangeablyCorey L, Wald A. In: Sexually Transmitted Diseases. 1999:Wald A et al. NEJM. 1995;333:Mertz GJ et al Ann Intern Med. 1992;116:References:Corey L, Wald A. Genital herpes. In: Holmes K, Sparling P, Mardh P, et al, eds. Sexually Transmitted Diseases. 3rd ed. New York, NY: McGraw-Hill;1999:Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med. 1995;333:Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992;116:
23Asymptomatic Viral Shedding is Common and Can Occur Frequently Most GH patients experience asymptomatic shedding*PCR has a ~3-4 times higher detection rate than culture% of patients with ≥ 1 day% of daysAsymptomatic shedding via culture† via PCR†51-61%2.0% - 6.6%72-88%7.8% - 27%Asymptomatic Viral Shedding is Common and Can Occur FrequentlyMost GH patients experience asymptomatic shedding*Asymptomatic shedding was detected at least once in 51-61% of patients via culture and 72-88% of patients via PCRAsymptomatic shedding occurs on % of days† by cultureAsymptomatic shedding occurs on 7.8% - 27% of days† by PCRPCR has a ~3-4 times higher detection rate than culture* Shedding in the absence of lesions† Shedding rates can vary based upon time since diagnosis, frequency of recurrences, method of detection, frequency/site of sampling* Shedding in the absence of lesions† Shedding rates can vary based upon time since diagnosis, frequency of recurrences, method of detection, frequency/site of samplingGupta R, et al. J Infect Dis. 2004; 190 (15):Wald A et al. N Engl J Med. 1995;333:Corey L et al. N Engl J Med. 2004;350:11-20.References:Gupta R, Wald A, Krantz E, et al. Valacyclovir and Acyclovir for Suppression of Shedding of Herpes Simplex Virus in the Genital Tract. J Infect Dis. 2004;190(15):Wald A, Zeh J, Selke SA, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med. 1995;333:Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20.Data on file, GlaxoSmithKline.
2450% of Asymptomatic Shedding 50% of Asymptomatic Shedding* Episodes Occurred More Than 7 Days From a LesionExamples+ Viral sheddingLesionsXViral Shedding Occurred in the Absence of LesionsViral shedding patterns illustrate why asymptomatic viral shedding can contribute so greatly to transmissionIn a study by Dr. Anna Wald in The New England Journal of Medicine in 1995, women were enrolled to obtain cultures from the genital tract and to keep a diary for symptoms or signs of genital herpes outbreaksWoman number 1 showed a pattern of shedding that was intermittentDay 8 this woman had a positive culture for HSV from the perianal areaDay 14 a positive culture was obtained from the vulvaDays 20, 21, and 23 positive cultures were obtained from the vulva in the absence of genital lesionsWoman number 2 had an outbreakShe intermittently shed virus during the period with visual lesions but shed virus from the perianal area 2 days after the lesions healedWoman number 3 shed virus for 4 days prior to the onset of lesions from multiple sitesWoman number 4 illustrates that a person can shed for multiple days in the absence of lesionsEven if she did a visual examination of her own external genitalia, she may not notice anything, as in this case where virus was shed from the cervix in the absence of lesions*Shedding in the absence of lesionsAdapted from Wald A et al. N Engl J Med. 1995;333:Reference:Wald A, Zeh J, Selke SA, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med. 1995;333:
25No reported history of symptomatic GH History of symptomatic GH Patients without a GH History Shed Asymptomatically* at a Similar Rate as Those with a HistoryNo reported history of symptomatic GHHistory of symptomatic GH32%No shedding39%No shedding68%Shedding61%SheddingHSV-2+ patientswith at least oneshedding episodePatients without a History of Symptomatic GH Shed Virus Asymptomatically* at a Similar Rate as Those with Symptomatic GH68% of HSV-2–positive patients WITHOUT a reported history of symptomatic GH shed virus asymptomatically at least once, while 61% of HSV-2–positive patients WITH a history of GH (median outbreaks = 4) shed virus asymptomatically at least once as measured by culture in this studyIn addition, the study found that asymptomatic viral shedding occurs at similar rates in patients with a history of genital herpes outbreaks as in those without.Whether or not HSV-2 positive patients have recognized outbreaks, most patients will shed virus at some point in time.And during asymptomatic shedding, because there are no symptoms, many patients can be unknowingly infectious to their partners* Shedding in the absence of lesionsIn addition, both groups shed virus asymptomatically at a similar rateWald A et al. NEJM. 2000;342:*shedding in the absence of lesions as measured by cultureReference:Wald A, Zeh J, Selke SA, et al. Reactivation of genital herpes simplex virus type 2 Infection in asymptomatic seropositive persons. N Engl J Med. 2000;342:
269.7% of Partners with HSV-2 Transmitted Genital Herpes to Their Susceptible Partners Study of 144 healthy couples discordant for genital herpes. Couples were followed for a median of 334 days:9.7% of Partners with HSV-2 Transmitted Genital Herpes to TheirSusceptible PartnersStudy of 144 heterosexual couples followed for a median of 334 days (28 to 1,122 days) in a failed vaccine trialPatients in this study were not on suppressive antiviral therapyPatients were counseled on safer sex practices and condom use during the course of the studyApproximately 10% of source partners transmitted genital herpes to their susceptible partner14 of 144 susceptible partners3 of 79 susceptible males11 of 65 susceptible females14 of 144 acquired genital herpes: 3 of 79 susceptible males of 65 susceptible femalesAdapted from Mertz GJ et al. Ann Intern Med. 1992;116:Reference:Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992;116:
27Up to 70% of Transmission May Occur During Asymptomatic Viral Shedding Transmission during asymptomaticviral sheddingUp to70%Up to30%In the same study with 14 of 144 transmissions, up to 70% (9 of 13) of transmissions occurred during periods of asymptomatic viral shedding. 4 of 13 transmissions occurred during periods with active symptoms, and one of the 14 transmissions occurred without any data about whether or not symptoms were present at the time of transmissionMost of those that transmitted genital herpes to their partner reported no signs or symptoms during recent sexual activity, thus supporting that patients can be infectious when not experiencing signs or symptoms of an outbreakTransmission during symptomaticoutbreaksResults from a randomized, prospective study of 144 healthy couples discordant for genital herpes. Couples were followed for a median of 334 days, during which time 9.7% of partners became infected with genital herpes.Adapted from Mertz GJ et al. Ann Intern Med. 1992;116:Reference:Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992;116:
28Common Manifestations of Genital Herpes “Classic” PresentationPainful vesiculopustular lesionsGenital ulcersPerianal and anal ulcersAtypical PresentationGenital ItchingVulvar, scrotal or perianal fissuresCervicitis or proctitisUrethral or vaginal dischargeVulvar or perianal irritationDysuriaPenile or scrotal irritationPainless ulcersAsymptomatic PresentationPatient EvaluationDiscussing genital herpes with a patient may be difficult; however, it is important to remember the majority of participants in the suburban prevalence study indicated they would like to know and that testing is an important part of managing their healthFor patients at risk for genital herpes, or presenting with signs or symptoms of an outbreak, it is important to be proactive in broaching the subject of genital herpesIt is also important to consider that patients require confidence when discussing their sexual history, genital symptoms, and current sexual practicesReassurance is important to any patient that is being worked up for genital herpesClinically, it is important to recognize that a genital herpes outbreak may present itself in many formsClassic presentation of genital herpes includes painful lesions, genital ulcers, and, perianal or anal ulcersMost genital herpes outbreaks are atypical. Ulcers may be painless or may not be present al all. A wide range of complaints (scrotal and perianal fissures, dysuria, etc.) can lead the clinician who conducts a careful exam to the tentative diagnosis of genital herpesAshley RL, Wald A. Clin Microbiol Rev. 1999;12:1-8.Reference:Ashley RL, Wald A. Genital Herpes: Review of the epidemic and potential use of type-specific serology. Clin Microbiol Rev. 1999;12:1-8.
29Commonly Misinterpreted Symptoms Women may misinterpret symptoms as1UTIYeast infectionHemorrhoidsIrritation from sex, condom use, or feminine productsMen may misinterpret symptoms as1Jock itchFolliculitisHemorrhoidsIrritation from condom use, sex, tight clothingTo best identify undiagnosed patients, it is important to be aware that such patients may present complaining of other ailments. Patients often mistake genital herpes outbreaks to be caused by other clinical conditions.Genital herpes outbreaks are often mistaken by men to beJock itchFolliculitisHemorrhoidsIrritation from condoms, sexual intercourse, or tight clothingGenital herpes outbreaks are often mistaken by women to beUTIYeast infectionIrritation from sexual intercourse, condom use, or feminine productsClinicians should have an elevated index of suspicion for genital herpes when patients present with complaints related to genitourinary symptoms.Have a high index of suspicion for GH in patients with recurrent genitourinary complaintsReference • 1. Ashley RL and Wald A. Clin Microbiol Rev. 1999;12:1-8.
30Possible Overlapping Symptoms Patient Reported Conditions Genital Herpes Signs and Symptoms Are Attributed to Many Other ConditionsUndiagnosed Patients Often Attribute Their Genital Herpes Symptoms to Other ConditionsItchingBurningRednessDischargePain with urinationUrinary frequency and urgencyUTIVaginitisYeastGenital HerpesPossible Overlapping SymptomsPatient Reported ConditionsActual DiagnosisGH Signs and Symptoms Are Attributed to Many Other ConditionsWhat People Say They Think They Have:Recurrent UTIs, recurrent vaginitis, recurrent yeast infectionsPatients with UTIs often experience frequency/urgency – these symptoms are not generally associated with genital herpesOther complaints can include menstrual complaints, hemorrhoids, heat rash, urethral syndrome, allergies, folliculitis, jock itch, ‘normal’ genital itch, zipper burn, allergies, various irritations and insect bitesPhysicians need to have a high index of suspicion when patients present or call the office with any of these complaintsIf a patient presents with these conditions repeatedly, consider testing for HSV-2Consider a differential diagnosis of genital herpes for patients with recurrent symptomsAshley RL, Wald A. Clin Microbiol Rev. 1999;12:1-8.Merck ManualReferences:Ashley RL, Wald A. Genital Herpes: Review of the epidemic and potential use of type-specific serology. Clin Microbiol Rev. 1999;12:1-8.Merck Manual
31First Episode Treatment Acyclovir 400 mg three times a day for7-10 days− Valacyclovir (Valtrex) 1000 mg twice a dayfor 7-10 days− Famciclovir (Famvir) 250 mg three times a day for 7-10 daysCDC Sexually Transmitted Diseases Guidelines19
32CDC Sexually Transmitted Diseases Guidelines. 2002. Episodic TherapyAcyclovir 400 mg TID for five days− Valtrex 500 mg BID for three to five days− Famvir 125 mg BID for five daysCDC Sexually Transmitted Diseases Guidelines20
33CDC Sexually Transmitted Diseases Guidelines. 2002. Suppressive TherapyAcyclovir 400 mg BID dailyValtrex 500 mg QD daily for people with 9 or fewer outbreaks per yearValtrex 500 mg BID or 1000 QD for people with 10 or more outbreaks per yearFamvir 250 mg BIDCDC Sexually Transmitted Diseases Guidelines21
34Long Term Suppression – Safety Issues Safety data available for up to 20 years of constant use (JID, Oct, 2002, Tyring)No safety labs need to be drawn (such as LFT, kidney functions)Drug holidays not needed23
35HSV Resistance is RareIsolation of resistant isolates is <<1% in immunocompetent patientsOnly a few documented cases of clinical resistanceNo detectable increase in resistance since introduction in 1981No documented cases of transmission of resistant virusMost resistant strains are deficient in viral thymidine kinase (TK-):these are less virulent than wild-type virus in animal models)Recent published model of antiviral resistance predicts that after 25 years of high antiviral use, only 5 of 10,000 immunocompetent patients will be shedding drug-resistant virusAcyclovir ResistanceThese slides will not be included in the promotional materialsKost RG et al. NEJM. 1993;329: Collins P, Ellis MN. J Med Virol. 1993;1(suppl 1): Mouly F et al. Dermatology. 1995;190:177. Corey L, Wald A. In: Sexually Transmitted Diseases. 1999:Bacon T et al. Clin Microbiol Rev. 2003;16: Gershengorn HB et al. BMC Inf Dis .2003;3:1References:Kost RG, Hill EL, Tigges M, Straus SE. Brief report: recurrent acyclovir-resistant genital herpes in animmunocompetent patient. N Engl J Med. 1993;329:Collins P, Ellis MN. Sensitivity monitoring of clinical isolates of herpes simplex virus to acyclovir. J Med Virol. 1993;1(suppl 1):58-66.Mouly F, Baccard M, Scieux C, et al. Chronic recurrent acyclovir-resistant genital herpes in an immunocompetent patient. Dermatology. 1995;190:177.Bacon TH, Levin MJ, Leary JL, Sarisky RT, Sutton D. Herpes Simplex Virus Resistance to Acyclovir and Penciclovir after Two Decades of Antiviral Therapy. Clin Microbiol Rev. 2003;16:Corey L, Wald A. Genital Herpes. In: Sexually Transmitted Diseases. 1999:
36HSV-2 Transmission Study Design Couples (N=1484)Source Partner Susceptible PartnerHSV-2 HSV-2Seropositive SeronegativeImmunocompetent, heterosexual partners, age ≥18, in a stable monogamous relationshipSource partner suitable for suppressive therapy, history of 9 or fewer episodes/yearSource partners randomized to valacyclovir 500 mg once daily or placebo for 8 monthsSusceptible partner monitored for acquisition of HSVStudy DesignThe study enrolled 1,484 monogamous couples discordant for HSV-2. The “source partner” was HSV-2 seropositive and the “susceptible partner” was HSV-2 seronegative. All partners in the study were immunocompetent, heterosexual, age 18 years or older, and were in a stable monogamous relationship.Source partners with 9 or fewer recurrences were randomized to receive treatment with either valacyclovir 500 mg once daily or placebo for a period of 8 months.At each monthly visit, couples were counseled to practice safer sex, including the use of condoms.Corey L et al. NEJM. 2004;350:11-20.Reference:Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20.
37Proportion of Susceptible Partners with Symptomatic Genital Herpes 0.511.522.5% with Clinical DiseasePlacebo Valacyclovir500 mg once daily2.2%(16/741)0.5%(4/743)P=0.011RR: 0.25 (95% CI: 0.08,0.74)75% reductionThe results of the study’s primary endpoint demonstrated a 75% reduction in the risk of transmission of symptomatic genital herpes among the valacyclovir group when compared to the placebo groupPlacebo group: 16/741 (2.2%)Valacyclovir (500 mg once daily) group: 4/743 (0.5%)The reduction in the risk of acquisition of symptomatic genital herpes in the susceptible partners with valacyclovir was statistically significant; P=0.011All patients with clinical disease had laboratory confirmation of HSV-2 seroconversion, culture, or PCRCorey L et al. NEJM. 2004;350:11-20.Reference:Data on file, GlaxoSmithKline.
38Proportion of Susceptible Partners with Overall Acquisition of HSV-2 Infection 1234Placebo Valacyclovir500 mg once daily3.6%1.9%% with HSV-2 Infection48% reductionP=0.054RR: 0.52 (95% CI: 0.27,0.97)(27/741)(14/743)The results of one of the study’s secondary endpoint demonstrated a 48% reduction in risk of overall acquisition in susceptible partners among the valacyclovir group when compared to the placebo groupPlacebo group: 27/741 (3.6%)Valacyclovir (500 mg once daily) group: 14/743 (1.9%): P=0.054Corey L et al. NEJM. 2004;350:11-20.Reference:Data on file, GlaxoSmithKline.
39Patients Infected <2 Years were More Likely to Infect Their Partner PlaceboValacyclovirPatients Infected for Less than 2 Years were More Likely to Infect Their PartnerTransmission study showed infection rates were higher among those infected for less than 2 years5.8% (8/137) of placebo patients infected for < 2 yrs transmitted to their partner vs 3.2% (19/602) for placebo patients infected ≥2 yrs3.1% (4/127) of patients infected for < 2 yrs taking valacyclovir transmitted to their partner vs 1.6% (10/613) of valacyclovir patients infected ≥ 2yrsDuration of InfectionCorey L et al. NEJM. 2004;350:11-20.Reference:Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20.
40Patients in Current Relationship for <1 Year were Also More Likely to Infect Their Partner PlaceboValacyclovirPatients in Current Relationship for Less than 1 Year were Also More Likely to Infect Their PartnerStudy showed the transmission rates were higher among those in their current relationship for less than 1 year5.8% (13/224) of placebo patients in the relationship for < 1yr infected their partner vs 2.7% (14/511) for placebo patients in current relationship ≥ 1 year2.8% (6/217) of valacyclovir patients in the relationship for < 1yr infected their partner vs 1.5% (8/520) for valacyclovir patients in current relationship ≥ 1 yearOther factors found to influence risk of transmission included being a female susceptible partner and having an increased number of sexual contacts.Duration of RelationshipCorey L et al. NEJM. 2004;350:11-20.Reference:Data on file, GlaxoSmithKline.
41HSV-2 Shedding Substudy Conducted in a subset of subjects enrolled in the main study89 source partners from 3 US sitesParticipated for ~ 60 daysDaily genital swabs for HSV-2 by PCRAdditional swab of lesion if presentConducted in a subset of subjects enrolled in the main study89 source partners from 3 US sitesParticipated for 60 daysDaily genital swabs for HSV-2 by PCRAdditional swab of lesion if presentReference:Data on file, GlaxoSmithKline.
42Placebo Valacyclovir P (N=50) (N=39) Value Source Partners Using Valacyclovir Shed on 73% Fewer Days Than Those on PlaceboPlacebo Valacyclovir P (N=50) (N=39) Value% of days with 10.8% 2.9% < total shedding* (mean)HSV DNA copies/mL < on all days (mean log10)64% fewer days of asymptomatic shedding† in the valacyclovir treatment group vs placebo (2.8% vs 7.8%, P<0.001)* Symptomatic and asymptomatic† Shedding in the absence of lesionsCorey L et al, NEJM 2004;350:11-20According to the study design, a substudy was performed to evaluate viral shedding and the effect of valacyclovir compared to placeboResults demonstrated that the valacyclovir group had significantly fewer days of total and asymptomatic viral shedding and less HSV DNA (mean log10) when compared to the placebo groupThe valacyclovir group had fewer days of viral shedding than the placebo group (P <0.001)Valacyclovir: 2.9% of days (mean) with sheddingPlacebo: 10.8% of days (mean) with sheddingThe valacyclovir group had less HSV DNA copies/mL on all days than the placebo group (P <0.001)Valacyclovir: 1.7 HSV DNA mean log10 copies/mLPlacebo: 4.2 HSV DNA mean log10 copies/mLReference:Data on file, GlaxoSmithKline.
43Revised ACOG Guideline Summary of Recommendations for Suppressive Therapy Use in GYN Patients (Level A):“Women with frequent recurrences should be offered suppressive therapy.”“For couples in which one partner has HSV-2 infection, suppressive antiviral therapy should be recommended for the partner with HSV-2 to reduce the rate of transmission.”ACOG Practice Bulletin No. 57November 2004Revised ACOG GuidelineSummary of Recommendations for Suppressive Therapy Use in GYN Patients (Level A recommendation) from the ACOG Practice Bulletin No. 57, issued Nov 2004:“Women with frequent recurrences should be offered suppressive therapy.”“For couples in which one partner has HSV-2 infection, suppressive antiviral therapy should be recommended for the partner with HSV-2 to reduce the rate of transmission.”Reference:ACOG Practice Bulletin No. 57, Vol 104, Nov. 2004,ACOG Practice Bulletin No. 57, Vol 104, Nov. 2004,
44VALTREX® (valacyclovir HCl): Dosage for Suppression of Genital Herpes In immunocompetent adults, the recommended dosage of VALTREX for chronic suppressive therapy of recurrent genital herpes is 1 g once daily with an alternative dose of 500 mg once daily for patients with 9 or fewer recurrencesThe safety and efficacy beyond one year has not been establishedMost commonly occurring adverse events with suppressive therapy include:headache (35% - 1 g, 38% mg, 34% - placebo)nausea (11%, 11%, 8%)abdominal pain (11%, 9%, 6%)VALTREX: Dosage for Suppression of Genital HerpesIn immunocompetent adults, the recommended dosage of VALTREX for chronic suppressive therapy of recurrent genital herpes is 1 g once daily with an alternative dose of 500 mg once daily for patients with 9 or fewer recurrencesThe safety and efficacy of suppressive therapy with VALTREX beyond one year has not been establishedMost commonly occurring adverse events with suppressive therapy include:headache (35% - 1 g, 38% mg, 34% - placebo)nausea (11%, 11%, 8%)abdominal pain (11%, 9%, 6%)References:Data on file, GlaxoSmithKline.
45Important Safety Information WARNING:Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), in some cases resulting in death, has occurred in patients with advanced HIV disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of VALTREX® (valacyclovir HCl) at doses of 8 g per dayWARNINGThrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), in some cases resulting in death, has occurred in patients with advanced HIV disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of VALTREX® (valacyclovir HCl) at doses of 8 g per day
46Important Safety Information (cont) Precautions:The safety and efficacy of VALTREX® (valacyclovir HCl) for reduction in the risk of transmission of genital herpes has not been established in nonheterosexual patients, patients with multiple sexual partners, or patients with more than 9 episodes per yearThe safety and efficacy of VALTREX for reduction in the risk of transmission of genital herpes has only been evaluated for 8 monthsPrecautionsThe safety and efficacy of VALTREX® (valacyclovir HCl) for reduction in the risk of transmission of genital herpes has not been established in nonheterosexual patients, patients with multiple sexual partners, or patients with more than 9 episodes per yearThe safety and efficacy of VALTREX for reduction in the risk of transmission of genital herpes has only been evaluated for 8 months
47Important Safety Information (cont) Precautions:When VALTREX® (valacyclovir HCl) is used to reduce the risk of transmission of genital herpes, patients should be counseled to use safer sex practices with suppressive therapy (see current CDC Sexually Transmitted Diseases Treatment Guidelines)VALTREX has not been shown to reduce the risk of transmission of sexually transmitted infections other than HSV-2There is no cure for genital herpes. Even with treatment, it may be possible to spread genital herpes to othersPrecautionsWhen VALTREX® (valacyclovir HCl) is used to reduce the risk of transmission of genital herpes, patients should be counseled to use safer sex practices with suppressive therapy (see current CDC Sexually Transmitted Diseases Treatment Guidelines)VALTREX has not been shown to reduce the risk of transmission of sexually transmitted infections other than HSV-2There is no cure for genital herpes. Even with treatment, it may be possible to spread genital herpes to others
48Creatinine clearance (mL/min) Dosage of VALTREX® (valacyclovir HCl) for Patients with Renal ImpairmentDosage adjustment recommended for patients with varying degrees of renal dysfunctionGenital herpesSuppressive 1 gram every No 500 mg every 500 mg every therapy 24 hours reduction 24 hours 24 hoursSuppressive 500 mg every No 500 mg every 500 mg every therapy 24 hours reduction 48 hours 48 hoursNormal dosage regimen (creatinine Indications clearance 50) <10Creatinine clearance (mL/min)Dosage of VALTREX (valacyclovir HCl) for Patients with Renal ImpairmentDosage adjustments recommended for patients with varying degrees of renal dysfunctionNormal dosage regimen (Creatinine clearance [CrCl] 50 mL/min) of 1 g q24hCrCl of mL/min: no reductionCrCl of mL/min: 500 mg q 24 hCrCl of <10 mL/min: 500 mg q 24 hNormal dosage regimen (CrCl 50 mL/min) of 500 mg q 24 hCrCl of mL/min: 500 mg q 48 hCrCl of <10 mL/min: 500 mg q 48 h
49ACOG Practice Bulletin Women with primary HSV during pregnancy should treat this episode with antiviral therapyCesarean delivery should be performed on women with first episode HSV or recurrent HSV who have active genital lesions or prodrome at deliveryFor women at or beyond 36 weeks gestation with a first episode of HSV occurring during pregnancy, antiviral therapy should be consideredFor HSV seropositive women at or beyond 36 weeks gestation and at risk of recurrent HSV, antiviral therapy may be considered, although such therapy may not reduce the likelihood of cesarean deliveryIn women with no active lesions or prodromal symptoms during labor, cesarean delivery should not be performed on the basis of a history of recurrent HSV disease.
50All pregnant women screened at 14-18 weeks gestation HSV SeronegativeHSV-1 SeropositiveHSV-2 SeropositivePartner HSV-1 SeropositivePartner HSV-2 SeropositiveAvoid oral-genital contactCondomsAbstinenceSuppression (partner)CondomsAbstinenceSuppression (partner)Exam for lesions in laborEducationSuppression (patient)Avoid if possibleAROMScalp electrodesVacuum extractorsForceps
51Interactions between HSV and HIV HSV-2 increases risk of HIV acquisitionHSV-2 increases risk of HIV transmissionHIV alters the natural history of HSV-2HSV-2 accelerates HIV progression
52Treatment Regimens Initial infection - Valacyclovir 1.0 g PO bid for 10 days- Famciclovir 250 mg PO tid for 10 days*- Acyclovir 400 mg PO tid* (or 200 mg PO 5 times daily) for 10 daysEpisodic therapy for recurrence- Valacyclovir 500 mg PO bid for 3 days- Famciclovir 125 mg PO bid for 5 days- Acyclovir 400 mg PO tid (or 200 mg PO 5 times daily) for 5 daysSuppressive therapy- Valacyclovir 500 mg PO daily †- Famciclovir 250 mg PO bid- Acyclovir 400 mg PO bid† Use 1.0g when >10 episodes per year* These are out-of-label regimens, listed by the CDC in the 2002 STD Guidelines for theTreatment of STDs