1. Genital Herpes: Clinical Update on Testing, Treatment and the Prevention of Transmission
Gary A. Richwald, MD, MPH
Clinical Virologist
Former Director and Chief Physician
Los Angeles County Sexually Transmitted Disease Program
Consultant, American Social Health Association
Medical Advisor – LA/Orange County HELP Groups

2. The Herpesvirus Family
Alphaherpesviruses
Herpes simplex virus type 1 (HSV-1)
Herpes simplex virus type 2 (HSV-2)
Varicella-zoster virus (VZV)
Betaherpesviruses
Cytomegalovirus (CMV)
Human herpesvirus 6 (HHV-6)
Human herpesvirus 7 (HHV-7)
Gammaherpesviruses
Epstein-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:

3. The Herpesviruses
The 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:

4. Genital Herpes is the Most Prevalent STI
Chlamydia
2 million
Hepatitis B
417,000
HPV
20 million
HIV
560,000
Genital Herpes (HSV-2)
45 million
Herpes is the Most Prevalent STD
Genital 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 year1-4
It is estimated that 1 in 5 Americans over the age of 14 (45 million) are infected with genital herpes1,4
Genital herpes is twice as prevalent as HPV
In 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 States3
Although genital herpes (GH) is one of the most common STDs, many primary care physicians believe it is virtually nonexistent in their patient population
1 Million New Genital Herpes (GH) Infections per Year in the US
Henry 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.

5. Suburban Seroprevalence of HSV-2
Study Design: six US communities, six private medical practices in each community: Atlanta, Baltimore, Boston, Chicago, Dallas, and Denver
Background: Many primary care providers believe genital herpes is not seen in their patient population
Objective: Determine seroprevalence of HSV-2 in suburban practices
150 patients per practice, equal number of men and women
Participation occurred as part of normal visit to office
75% Caucasian, 14% African-American, 4% Hispanic
45% household income >$60,000/year, 35% college grad
Participation level very high
Significance of HSV-2 Seroprevalence Findings
The 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 positive
Therefore, 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 partners
Leone 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.

6. Suburban Seroprevalence of HSV-2
Less than 5% of year old patients
report being told they have genital herpes
Patients (%)
Known History of HSV-2 Seroprevalence Rates
All 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 herpes
4.3%
N=5,433
Patients acknowledge
they have GH
Leone P. Sex Transm Dis 2004;31(5):
Reference:
Data on file, GlaxoSmithKline.

7. 88% did NOT know they had GH
Suburban Seroprevalence of HSV-2 9 Out of 10 Did Not Know They Had Genital Herpes
12% reported having GH
Patients (%)
N=5,452
Patients seropositive for HSV-2 0%
10%
20%
30%
40%
25.5%
9 Out of 10 Did Not Know They Had GH
In 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 Findings
96% of people wanted to know if they are infected with HSV-2
Most 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%, respectively
Age bracket  years were at greater risk than participants years old
African-American race
Less than a post graduate education
Higher number of lifetime sexual partners
Parameters of geographic region when adjusted for race/ethnicity, employment, income, and marital status had no effect on prevalence rates
88% did NOT know they had GH
Leone 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.

8. The Significance of Genital Herpes
May cause physical and psychological concerns (1)
HSV-2 infection increases the risk of HIV-1 infection by
at least 2-fold, possibly as much as 4-fold (2)
Impact on social health
89% expressed concern and anxiety about transmitting to a partner (3)
Transmission of herpes to newborn during pregnancy or delivery
occurs in 1 per 3,200 live births (4)
may lead to serious complications such as seizures, blindness, psychomotor retardation, spasticity, learning disabilities, and death2
The Significance of Genital Herpes
The diagnosis of HSV-2 infection may cause may cause physical and psychological concerns1
In addition, HSV-2 infection Increases the risk of acquiring a HIV-1 infection by 2-fold2
Genital herpes impacts social health, and 89% of patients have expressed concern over transmitting the virus to their sexual partners3
Transmission of herpes to newborn during delivery can lead to serious complications in 1 per 3,200 live births4
Serious complications include seizures, blindness, psychomotor retardation, spasticity, learning disabilities, and death
1. CDC Sexually Transmitted Diseases Guidelines
2. 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:

9. Herpes 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 acquisition
HSV-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 acquisition
Differences in HSV-1 and HSV-2 Genital Infection
It 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.

10. Type-Specific Methods for Diagnosing Genital Herpes
Swab symptomatic area to detect virus
Culture
Polymerase Chain Reaction (PCR)
Draw blood to look for type-specific antibodies
There are Several Type Specific Methods for Diagnosing Genital Herpes
There are 3 main methods to confirm a genital herpes diagnosis.
Swab symptomatic area to detect virus
Culture
Polymerase Chain Reaction (PCR)
Request typing for samples analyzed via culture or PCR
Blood draw to detect antibodies using approved IgG type specific serology tests:
Western Blot: The gold standard
HerpeSelect® IgG ELISA HSV-1 or -2
HerpeSelect® IgG Immunoblot HSV-1 and -2
biokitHSV-2 Rapid Test
Captia 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.

11. Detection of Virus Using a Swab of Lesion/Infected Area
Culture: if results are non type-specific, request lab to perform typing
Not useful during intra-lesional period
If Positive:
Patient likely has GH; false positives are very rare
If Negative:
No detectable virus in that sample; does NOT mean patient doesn’t have GH
False 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 low
There are two methods of detecting virus using a swab – culture and PCR.
CULTURE
Viral culture is the gold standard for diagnosing genital herpes. If the culture is positive, patient likely has GH; false positives rare
However 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 PCR
PCR
The 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 rare
False negatives are rare
If the result is negative, it does NOT mean patient doesn’t have GH – it just means there was no virus in that sample
References:
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:

12. Detection 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 rare
If Negative:
False negatives are rare
No virus in sample taken; patient could still have GH
Ashley 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:

13. Detection of HSV-2 Antibody Using Type-Specific Serology
Principal test:
FDA-approved IgG type-specific antibody tests
• HerpeSelect® ELISA HSV-2 or HSV-1
HerpeSelect® Immunoblot for HSV-2 and HSV-1
biokit HSV-2 Rapid Test
Much less commonly used TSST:
Western blot
First type-specific test, not FDA approved
Not commercially available but can be sent to Univ. of Washington
Detection of HSV-2 Antibody Using Type Specific Serology
When 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 Specificity
Western Blot HSV
HerpeSelect ELISA
HerpeSelect Immunoblot HSV
biokitHSV-2 only
Captia 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.

14. HerpeSelect-2 and HerpeSelect-1 Type-Specific Tests

15. Genital Herpes: FDA-Approved Type-Specific Serologic Tests
Sensitivity* Specificity* (%) (%) `
Type of Test
HerpeSelectTM 2 ELISA IgG HerpeSelectTM 1 ELISA IgG
HerpeSelectTM
Immunoblot 2
Immunoblot 1
Accurate 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 antibodies
HerpeSelectTM is a trademark of Focus Diagnostics
Adapted from Ashley RL. Sex Transm Infect. 2001;77:
Ashley-Morrow R et al. Am J Clin Pathol; 2003;120
Reference:
Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect. 2001;77:

16. Test Order Codes for HerpeSelect® 1 and 2 IgG Type-Specific Antibodies
Quest Diagnostics
Runs only HerpeSelect IgG serology
HSV-2 alone, HSV-1 alone, or the combination
Order codes:
HerpeSelect HSV-1 ELISA: X
HerpeSelect HSV-2 ELISA: X
HSV-1 and HSV-2 combined: X
Labcorp
Runs non-specific as well as type-specific HerpeSelect tests
HerpeSelect 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: 84429
Test Order Codes for the HerpeSelect® ELISA HSV-2 and HSV-1 at Two Major Labs
Two of the largest labs run HerpeSelect
Quest Diagnostics
runs only HerpeSelect
HSV-2 alone, HSV-1 alone, or the combination
Order codes for majority of Quest sites:
HerpeSelect HSV-2 ELISA: 3640
HerpeSelect HSV-1 ELISA: 3636
HSV-1 and HSV-2 together: 6447
Codes vary by facility; confirm code with lab before ordering
LabCorp
first performs HSV test that is not type specific
if sample tests HSV+, run HerpeSelect HSV-2 type-specific test
Possible order codes: or

17. Is 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 test
Why aren’t IgM tests helpful in determining the recency of
GH infection?
- IgM tests are not type-specific – IgM could be from HSV-1
or HSV-2!
- Each of the many episodes of viral reactivation can
produce new IgM and IgG, making it difficult to interpret
results as to acuity of infection. For example, some first
infections can have no IgM (only IgG) and some recurrent
infections 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 herpes
Cannot distinguish primary from recurrent infection
Does not distinguish type 1 from type 2
In 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.
Reference
Ashley RL. Type-specific antibodies to HSV-1 and 2: review of methodology. Herpes 1998;5:33–38.

18. Who Is a Candidate for HSV Serologic Testing?
Patient with typical GH lesion; culture not done or negative
Patient with recurrent clinical symptoms suggestive of GH, but without typical GH lesions
Sexual partners of patients with GH
Patient request to know infection status
STD screening
Prenatal screening
Patient with HIV infection
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 infected
Someone who has suspicious symptoms
Someone who has been diagnosed by visual inspection and doesn’t believe it
Anyone getting an STD screen
Parents of babies with neonatal herpes.
Reference:
Diagnosing genital herpes. Diagnology. Available at Accessed March 16, 2001.

19. Who Is a Candidate for HSV Serologic Testing
Who Is a Candidate for HSV Serologic Testing? Persons with clinical evidence of HSV
Patient has typical GH lesion; culture/PCR not done or negative
Patient originally diagnosed with HSV by clinical exam only without culture/PCR
Patient 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 infected
Someone who has suspicious symptoms
Someone who has been diagnosed by visual inspection and doesn’t believe it
Anyone getting an STD screen
Parents of babies with neonatal herpes.
Reference:
Diagnosing genital herpes. Diagnology. Available at Accessed March 16, 2001.

20. Who Is a Candidate for HSV Serologic Testing
Who Is a Candidate for HSV Serologic Testing? Testing driven by patient risk-profile or request
Patient with a previous or a current partner with GH
Patient needs STD screening due to risk status
Patient requests STD screening
Patient requests HSV testing
Patient is being evaluated for sexual assault
Note: 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).

21. Who Is a Candidate for HSV Serologic Testing? Special populations
Pregnant women
Patients prior to transplant or starting immunosuppressive therapy
Patients with HIV infection
Patients at risk for sexual acquisition of HIV infection
Note: 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.

22. Asymptomatic Viral Shedding
Asymptomatic viral shedding is the presence of HSV on the surface of the skin/mucosa in the absence of signs and symptoms
Subclinical shedding may occur in the presence of symptoms such as itching or tingling without any apparent lesions
The majority of people with genital HSV-2 shed virus asymptomatically; frequency of shedding is highest
in first few years after acquisition
Possible 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 lesion
However, the virus can also be transmitted when a patient has virus present on the skin without lesions or symptoms
Asymptomatic viral shedding is the presence of HSV on the surface of the skin/mucosa in the absence of signs and symptoms
Subclinical shedding may occur in the presence of symptoms such as itching or tingling without any apparent lesions
Many clinicians use these terms interchangeably
Corey 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:

23. Asymptomatic 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 days
Asymptomatic shedding via culture† via PCR†
51-61%
2.0% - 6.6%
72-88%
7.8% - 27%
Asymptomatic Viral Shedding is Common and Can Occur Frequently
Most 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 PCR
Asymptomatic shedding occurs on % of days† by culture
Asymptomatic shedding occurs on 7.8% - 27% of days† by PCR
PCR 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 sampling
Gupta 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.

24. 50% of Asymptomatic Shedding
50% of Asymptomatic Shedding* Episodes Occurred More Than 7 Days From a Lesion
Examples
+ Viral shedding
Lesions X
Viral Shedding Occurred in the Absence of Lesions
Viral shedding patterns illustrate why asymptomatic viral shedding can contribute so greatly to transmission
In 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 outbreaks
Woman number 1 showed a pattern of shedding that was intermittent
Day 8 this woman had a positive culture for HSV from the perianal area
Day 14 a positive culture was obtained from the vulva
Days 20, 21, and 23 positive cultures were obtained from the vulva in the absence of genital lesions
Woman number 2 had an outbreak
She intermittently shed virus during the period with visual lesions but shed virus from the perianal area 2 days after the lesions healed
Woman number 3 shed virus for 4 days prior to the onset of lesions from multiple sites
Woman number 4 illustrates that a person can shed for multiple days in the absence of lesions
Even 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 lesions
Adapted 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:

25. No reported history of symptomatic GH History of symptomatic GH
Patients without a GH History Shed Asymptomatically* at a Similar Rate as Those with a History
No reported history of symptomatic GH
History of symptomatic GH
32%
No shedding
39%
No shedding
68%
Shedding
61%
Shedding
HSV-2+ patients
with at least one
shedding episode
Patients without a History of Symptomatic GH Shed Virus Asymptomatically* at a Similar Rate as Those with Symptomatic GH
68% 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 study
In 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 lesions
In addition, both groups shed virus asymptomatically at a similar rate
Wald A et al. NEJM. 2000;342:
*shedding in the absence of lesions as measured by culture
Reference:
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:

26. 9.7% 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 Their
Susceptible Partners
Study of 144 heterosexual couples followed for a median of 334 days (28 to 1,122 days) in a failed vaccine trial
Patients in this study were not on suppressive antiviral therapy
Patients were counseled on safer sex practices and condom use during the course of the study
Approximately 10% of source partners transmitted genital herpes to their susceptible partner
14 of 144 susceptible partners
3 of 79 susceptible males
11 of 65 susceptible females
14 of 144 acquired genital herpes: 3 of 79 susceptible males of 65 susceptible females
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:

27. Up to 70% of Transmission May Occur During Asymptomatic Viral Shedding
Transmission during asymptomatic
viral shedding
Up to
70%
Up to
30%
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 transmission
Most 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 outbreak
Transmission during symptomatic
outbreaks
Results 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:

28. Common Manifestations of Genital Herpes
“Classic” Presentation
Painful vesiculopustular lesions
Genital ulcers
Perianal and anal ulcers
Atypical Presentation
Genital Itching
Vulvar, scrotal or perianal fissures
Cervicitis or proctitis
Urethral or vaginal discharge
Vulvar or perianal irritation
Dysuria
Penile or scrotal irritation
Painless ulcers
Asymptomatic Presentation
Patient Evaluation
Discussing 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 health
For 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 herpes
It is also important to consider that patients require confidence when discussing their sexual history, genital symptoms, and current sexual practices
Reassurance is important to any patient that is being worked up for genital herpes
Clinically, it is important to recognize that a genital herpes outbreak may present itself in many forms
Classic presentation of genital herpes includes painful lesions, genital ulcers, and, perianal or anal ulcers
Most 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 herpes
Ashley 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.

29. Commonly Misinterpreted Symptoms
Women may misinterpret symptoms as1
UTI
Yeast infection
Hemorrhoids
Irritation from sex, condom use, or feminine products
Men may misinterpret symptoms as1
Jock itch
Folliculitis
Hemorrhoids
Irritation from condom use, sex, tight clothing
To 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 be
Jock itch
Folliculitis
Hemorrhoids
Irritation from condoms, sexual intercourse, or tight clothing
Genital herpes outbreaks are often mistaken by women to be
UTI
Yeast infection
Irritation from sexual intercourse, condom use, or feminine products
Clinicians 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 complaints
Reference • 1. Ashley RL and Wald A. Clin Microbiol Rev. 1999;12:1-8.

30. Possible Overlapping Symptoms Patient Reported Conditions
Genital Herpes Signs and Symptoms Are Attributed to Many Other Conditions
Undiagnosed Patients Often Attribute Their Genital Herpes Symptoms to Other Conditions
Itching
Burning
Redness
Discharge
Pain with urination
Urinary frequency and urgency
UTI
Vaginitis
Yeast
Genital Herpes 
Possible Overlapping Symptoms
Patient Reported Conditions
Actual Diagnosis
GH Signs and Symptoms Are Attributed to Many Other Conditions
What People Say They Think They Have:
Recurrent UTIs, recurrent vaginitis, recurrent yeast infections
Patients with UTIs often experience frequency/urgency – these symptoms are not generally associated with genital herpes
Other complaints can include menstrual complaints, hemorrhoids, heat rash, urethral syndrome, allergies, folliculitis, jock itch, ‘normal’ genital itch, zipper burn, allergies, various irritations and insect bites
Physicians need to have a high index of suspicion when patients present or call the office with any of these complaints
If a patient presents with these conditions repeatedly, consider testing for HSV-2
Consider a differential diagnosis of genital herpes for patients with recurrent symptoms
Ashley RL, Wald A. Clin Microbiol Rev. 1999;12:1-8.
Merck Manual
References:
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

31. First Episode Treatment
Acyclovir 400 mg three times a day for
7-10 days
− Valacyclovir (Valtrex) 1000 mg twice a day
for 7-10 days
− Famciclovir (Famvir) 250 mg three times a day for 7-10 days
CDC Sexually Transmitted Diseases Guidelines 19

32. CDC Sexually Transmitted Diseases Guidelines. 2002.
Episodic Therapy
Acyclovir 400 mg TID for five days
− Valtrex 500 mg BID for three to five days
− Famvir 125 mg BID for five days
CDC Sexually Transmitted Diseases Guidelines 20

33. CDC Sexually Transmitted Diseases Guidelines. 2002.
Suppressive Therapy
Acyclovir 400 mg BID daily
Valtrex 500 mg QD daily for people with 9 or fewer outbreaks per year
Valtrex 500 mg BID or 1000 QD for people with 10 or more outbreaks per year
Famvir 250 mg BID
CDC Sexually Transmitted Diseases Guidelines 21

34. Long 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 needed 23

35. HSV Resistance is Rare
Isolation of resistant isolates is <<1% in immunocompetent patients
Only a few documented cases of clinical resistance
No detectable increase in resistance since introduction in 1981
No documented cases of transmission of resistant virus
Most 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 virus
Acyclovir Resistance
These slides will not be included in the promotional materials
Kost 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;3:1
References:
Kost RG, Hill EL, Tigges M, Straus SE. Brief report: recurrent acyclovir-resistant genital herpes in an
immunocompetent 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:

36. HSV-2 Transmission Study Design
Couples (N=1484)
Source Partner Susceptible Partner
HSV-2 HSV-2
Seropositive Seronegative
Immunocompetent, heterosexual partners, age ≥18, in a stable monogamous relationship
Source partner suitable for suppressive therapy, history of 9 or fewer episodes/year
Source partners randomized to valacyclovir 500 mg once daily or placebo for 8 months
Susceptible partner monitored for acquisition of HSV
Study Design
The 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.

37. Proportion of Susceptible Partners with Symptomatic Genital Herpes
0.5 1
1.5 2
2.5
% with Clinical Disease
Placebo Valacyclovir
500 mg once daily
2.2%
(16/741)
0.5%
(4/743)
P=0.011
RR: 0.25 (95% CI: 0.08,0.74)
75% reduction
The 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 group
Placebo 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=0.011
All patients with clinical disease had laboratory confirmation of HSV-2 seroconversion, culture, or PCR
Corey L et al. NEJM. 2004;350:11-20.
Reference:
Data on file, GlaxoSmithKline.

38. Proportion of Susceptible Partners with Overall Acquisition of HSV-2 Infection1 2 3 4
Placebo Valacyclovir
500 mg once daily
3.6%
1.9%
% with HSV-2 Infection
48% reduction
P=0.054
RR: 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 group
Placebo group: 27/741 (3.6%)
Valacyclovir (500 mg once daily) group: 14/743 (1.9%): P=0.054
Corey L et al. NEJM. 2004;350:11-20.
Reference:
Data on file, GlaxoSmithKline.

39. Patients Infected <2 Years were More Likely to Infect Their Partner
Placebo
Valacyclovir
Patients Infected for Less than 2 Years were More Likely to Infect Their Partner
Transmission study showed infection rates were higher among those infected for less than 2 years
5.8% (8/137) of placebo patients infected for < 2 yrs transmitted to their partner vs 3.2% (19/602) for placebo patients infected ≥2 yrs
3.1% (4/127) of patients infected for < 2 yrs taking valacyclovir transmitted to their partner vs 1.6% (10/613) of valacyclovir patients infected ≥ 2yrs
Duration of Infection
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.

40. Patients in Current Relationship for <1 Year were Also More Likely to Infect Their Partner
Placebo
Valacyclovir
Patients in Current Relationship for Less than 1 Year were Also More Likely to Infect Their Partner
Study showed the transmission rates were higher among those in their current relationship for less than 1 year
5.8% (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 year
2.8% (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 year
Other factors found to influence risk of transmission included being a female susceptible partner and having an increased number of sexual contacts.
Duration of Relationship
Corey L et al. NEJM. 2004;350:11-20.
Reference:
Data on file, GlaxoSmithKline.

41. HSV-2 Shedding Substudy
Conducted in a subset of subjects enrolled in the main study
89 source partners from 3 US sites
Participated for ~ 60 days
Daily genital swabs for HSV-2 by PCR
Additional swab of lesion if present
Conducted in a subset of subjects enrolled in the main study
89 source partners from 3 US sites
Participated for 60 days
Daily genital swabs for HSV-2 by PCR
Additional swab of lesion if present
Reference:
Data on file, GlaxoSmithKline.

42. Placebo Valacyclovir P (N=50) (N=39) Value
Source Partners Using Valacyclovir Shed on 73% Fewer Days Than Those on Placebo
Placebo 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 lesions
Corey L et al, NEJM 2004;350:11-20
According to the study design, a substudy was performed to evaluate viral shedding and the effect of valacyclovir compared to placebo
Results 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 group
The valacyclovir group had fewer days of viral shedding than the placebo group (P <0.001)
Valacyclovir: 2.9% of days (mean) with shedding
Placebo: 10.8% of days (mean) with shedding
The 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/mL
Placebo: 4.2 HSV DNA mean log10 copies/mL
Reference:
Data on file, GlaxoSmithKline.

43. Revised 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. 57
November 2004
Revised ACOG Guideline
Summary 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,

44. VALTREX® (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 recurrences
The safety and efficacy beyond one year has not been established
Most 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 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 recurrences
The safety and efficacy of suppressive therapy with VALTREX beyond one year has not been established
Most 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.

45. Important 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 day
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 day

46. Important 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 year
The safety and efficacy of VALTREX for reduction in the risk of transmission of genital herpes has only been evaluated for 8 months
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 year
The safety and efficacy of VALTREX for reduction in the risk of transmission of genital herpes has only been evaluated for 8 months

47. Important 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-2
There is no cure for genital herpes. Even with treatment, it may be possible to spread genital herpes to others
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-2
There is no cure for genital herpes. Even with treatment, it may be possible to spread genital herpes to others

48. Creatinine clearance (mL/min)
Dosage of VALTREX® (valacyclovir HCl) for Patients with Renal Impairment
Dosage adjustment recommended for patients with varying degrees of renal dysfunction
Genital herpes
Suppressive 1 gram every No 500 mg every 500 mg every therapy 24 hours reduction 24 hours 24 hours
Suppressive 500 mg every No 500 mg every 500 mg every therapy 24 hours reduction 48 hours 48 hours
Normal dosage regimen (creatinine Indications clearance 50) <10
Creatinine clearance (mL/min)
Dosage of VALTREX (valacyclovir HCl) for Patients with Renal Impairment
Dosage adjustments recommended for patients with varying degrees of renal dysfunction
Normal dosage regimen (Creatinine clearance [CrCl]  50 mL/min) of 1 g q24h
CrCl of mL/min: no reduction
CrCl of mL/min: 500 mg q 24 h
CrCl of <10 mL/min: 500 mg q 24 h
Normal dosage regimen (CrCl  50 mL/min) of 500 mg q 24 h
CrCl of mL/min: 500 mg q 48 h
CrCl of <10 mL/min: 500 mg q 48 h

49. ACOG Practice Bulletin
Women with primary HSV during pregnancy should treat this episode with antiviral therapy
Cesarean delivery should be performed on women with first episode HSV or recurrent HSV who have active genital lesions or prodrome at delivery
For women at or beyond 36 weeks gestation with a first episode of HSV occurring during pregnancy, antiviral therapy should be considered
For 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 delivery
In 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.

50. All pregnant women screened at 14-18 weeks gestation
HSV Seronegative
HSV-1 Seropositive
HSV-2 Seropositive
Partner HSV-1 Seropositive
Partner HSV-2 Seropositive
Avoid oral-genital contact
Condoms
Abstinence
Suppression (partner)
Condoms
Abstinence
Suppression (partner)
Exam for lesions in labor
Education
Suppression (patient)
Avoid if possible
AROM
Scalp electrodes
Vacuum extractors
Forceps

51. Interactions between HSV and HIV
HSV-2 increases risk of HIV acquisition
HSV-2 increases risk of HIV transmission
HIV alters the natural history of HSV-2
HSV-2 accelerates HIV progression

52. Treatment 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 days
Episodic 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 days
Suppressive 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 the
Treatment of STDs

53. Gary Richwald, MD, MPH