2. 1 Seroprevalence of HSV-2 in Suburban Primary Care Offices Douglas T. Fleming, MD

3. 2 Acknowledgements  Authors: P. Leone, A. Gilsenan, L. Li, S. Justus  Staff from the following organizations: RTI Health Solutions, Quest Diagnostics Clinical Trials, American Social Health Association, and GlaxoSmithKline  Investigators, staff and patients from the 36 study sites

4. 3 Background  HSV-2 infection is common: 21.9% of the United States population age >=12 in the early 1990s  In the same study, only ~9% of seropositives reported that they had “ever had genital herpes” Fleming D, et al; New England Journal of Medicine, vol. 337, no. 16, October 1997, pp. 1105-11

5. 4 Background (continued)  The great majority of HSV-2 seropositive people experience outbreaks – most unrecognized – with symptoms or viral shedding or both  Genital herpes can cause devastating disease in neonates and immunosuppressed people, and appears to facilitate HIV transmission Wald A, et al; N Engl J Med, vol. 342, no. 12, March 2000, pp. 844-50 Fleming D and Wasserheit J; Sexually Transmitted Infections, vol. 75, no. 1, February 1999, pp. 3-17.

6. 5 Background (continued)  Many primary care physicians believe that the HSV-2 seroprevalence rates in national surveys do not apply to their patient populations, and that very few of their patients have genital herpes  Anecdotal evidence suggests that this belief is especially strong in more affluent suburban areas

7. 6 Objectives  Provide HSV-2 seroprevalence estimates from a sample of adults attending PCP offices in suburban areas of 6 U.S. communities  Describe the demographic and behavioral correlates of genital herpes in this population

8. 7 Methods  Weighted HSV-2 seroprevalence study  Target sample size: 5,400  Adults 18 - 59 years of age  Not known to be pregnant

9. 8 Methods 6 U.S. suburban communities

10. 9 Methods  In each of the six metropolitan areas, sampling design began with relatively affluent U.S. Census Tracts, defined as those with above-median values for –Home ownership –Household income –Housing value

11. 10 Methods  Within the group of these census tracts in each metropolitan area, six PCP offices were sampled  Between 21 and 76 eligible PCP offices were contacted in each metropolitan area in order to recruit the six participating offices. Little information was available on non- participating offices.  Total clinic sample: 36 PCP offices

12. 11 Methods  150 subjects per PCP office  2 Genders: 75 male / 75 female  4 Age groups: 18 - 29, 30 -39, 40 - 49, 50 – 59  Total: 8 cells (=2 x 4)  For weighting purposes, field interviewers counted patients in each cell visiting each office over a 2-week period

13. 12 Methods  Patients were recruited during a normal clinic visit  Clinic Staff provided information card to all eligible patients upon check-in, and referred interested subjects to an on-site field interviewer  Field interviewers screened subjects, obtained informed consent, and coordinated collection of data

14. 13 Methods Subjects …..  Provided a blood sample for HSV-2 serology testing, and  Filled out a questionnaire

15. 14 Methods Type-specific HSV-2 serology  FOCUS HerpeSelect 2 ELISA IgG kit  Processed at central laboratory

16. 15 Methods  All subject-specific results (HSV-2 Ab) undisclosed to PCP, clinic staff, or study sponsor  HSV-2 Ab results & counseling services were available to subjects via a toll-free anonymous call to the American Social Health Association

17. 16 Methods  Patients filled out a risk assessment questionnaire using Audio Computer- Assisted Self-Interviewing (ACASI)  Included questions on demographics, sexual behaviors, knowledge and beliefs, and symptoms

18. 17 Methods  Results were weighted to the estimated total sample of patients entering physicians’ offices in suburban areas within the selected cities  Analyzed in SUDAAN

19. 18 Study Sample: Gender and Age  Total sample: N=5452  Per the study design, sample was distributed nearly equally –among males and females, and –among the four age groupings

20. 19 Study Sample: Race/Ethnicity  Caucasian75.0%  African-American14.2%  Asian2.8%  Hispanic4.3%  American Indian0.7%  Mixed Race or Other2.9% [Self-reported by respondents: “Please select the one category that most closely applies to you”]

21. 20 Study Sample: Demographics  Married57.3%  Employed full- or part-time79.6%  Some college, tech/prof.,73.6% or more education  > $60,000 in total household income44.9%  Private/employer provided insurance81.8%

22. 21 RESULTS

23. 22 HSV-2 Seroprevalence Rates  Overall25.5% (20.2-30.8)  Gender Male22.0% (17.3-26.7) Female28.3% (22.0-34.6)  Age group 18-2913.4% (9.3-17.5) 30-3925.2% (18.3-32.1) 40-4931.2% (27.5-34.9) 50-5928.0% (20.2-35.8)

24. 23 HSV-2 Seroprevalence by Gender and Age Age Group (Year) HSV-2 Seroprevalence (%)

25. 24 Race / Ethnicity HSV-2 Seroprevalence (%) Seroprevalence Rates by Race/Ethnicity

26. 25 Seroprevalence Rates by Marital Status Marital Status HSV-2 Seroprevalence (%)

27. 26 Other Demographic Variables

28. 27 Seroprevalence Rates by Highest Educational Level Attained Educational Level HSV-2 Seroprevalence (%)

29. 28 Seroprevalence Rates by Total Household Income in 2001 Household Income HSV-2 Seroprevalence (%)

30. 29 Seroprevalence Rates by Region Region HSV-2 Seroprevalence (%)

31. 30 Behavioral Variables

32. 31 HSV-2 Seroprevalence Rates by Age at First Intercourse Age First Intercourse HSV-2 Seroprevalence (%)

33. 32 HSV-2 Seroprevalence by Gender and Lifetime No. of Sex Partners* *age-adjusted to US population Lifetime No. Sex Partners HSV-2 Seroprevalence (%)

34. 33 History of Genital Herpes

35. 34 History of Genital Herpes  “Have you ever been told you have Genital Herpes?” Percent that answered “Yes”: Overall4.3% Males3.4% Females5.1%

36. 35 History of Genital Herpes  Percent of HSV-2-seropositives with a known history of genital herpes: Overall11.9% Males11.6% Females12.1%

37. 36 Multivariate Analysis: Predictors of HSV-2 Serostatus

38. 37 Predictors of HSV-2 Serostatus Gender Age Race/Ethnicity Marital Education Income Region Age at First Intercourse Lifetime # Partners X X X X

39. 38 Limitations  Non-random factors may have operated in determining the sample of (1) physician offices, and (2) patients who volunteered  Little is known about non-participants (partly because of HIPAA regulations)  However…. –There is no a priori reason to suspect bias –Interviewers anecdotally reported high interest rates in all groups.

40. 39 Limitations (cont’d) HerpesSelect 2 May Have Overestimated Prevalence by 1-2% (Absolute) Versus Gold Standard (Western Blot) Per HerpesSelect 2 package Insert: Sensitivity.=96.1%, Specificity=97%

41. 40 Conclusions and Recommendations

42. 41 Conclusions  Among patients visiting their primary care physicians in these relatively affluent suburban areas, HSV-2 infection was.. –common (25.5%), but –largely unrecognized (herpes history in 11% of seropositives)

43. 42 Conclusions  Especially strong independent predictors of HSV-2 seroprevalence were –Age –Race/ethnicity –Lifetime number of sexual partners  Marked regional differences in HSV-2 seroprevalence were no longer significant after adjustment for other predictors

44. 43 Recommendations  Improve appreciation of the high prevalence of HSV-2 infection, even in populations often considered at “low risk”  Improve recognition of genital herpes by clinicians, since –Few seropositives were aware of their infection, despite access to health care –Once a person with GH is able to recognize outbreaks, he or she can take steps that may help avoid infecting partners or neonates

45. 44 Future Directions Analyses of the dataset are ongoing. Themes to explore include:  Predictors of a known history of genital herpes among HSV-2 seropositives  Relationship of HSV-2 serostatus to recent history of nonspecific symptoms such as dysuria, genital itch, and discharge.

46. 45 Q&A

47. 46 Acknowledgements  Authors: D. Fleming, P. Leone, A. Gilsenan, L. Li, S. Justus  Staff from the following organizations: RTI Health Solutions, Quest Diagnostics Clinical Trials, American Social Health Association, and GlaxoSmithKline  Investigators, staff and patients from the 36 study sites

48. 47 Backup/Optional slides

49. 48 NHANES III vs. HS240024 % HSV-2 Seroprevalence OverallCaucasianAfr.-Americans NHANES III Both: 21.917.645.9 Male: 17.814.934.7 Female: 25.620.255.1 HS240024 Both: 25.520.652.4 Male: 22.018.242.6 Female: 28.322.659.4

50. 49 Subject Disposition Total screened5,732 Ineligible107 Refusal111 Enrolled5,514 Interviewed - no blood specimen37 Problems with blood specimen25 Population for prevalence estimates5,452 Provide blood specimen19 Population for risk modeling5,433

51. 50 Why Subjects Did Not Participate...  Ineligible: out of age range  Ineligible: language barrier  Ineligible: age/gender cell full  Ineligible: pregnant woman  Refusal: no reason given  Refusal: no time  Refusal: not interested  Refusal: too sensitive/personal  Refusal: due to venipuncture required

52. 51 Inclusion / Exclusion Criteria  Male or female  18 - 59 years of age  Able to read and comprehend English in order to complete the Risk Assessment Questionnaire  Must be visiting their physician’s office due to illness or injury, annual physical examination, etc.; for any reason except explicitly to enroll  Must be willing and able to provide written informed consent and comply with the protocol

53. 52 Assessments / Procedures  Demographic information obtained  Completion of Risk Assessment Questionnaire for subsequent analysis of data  Field Interviewers: to interact with subjects & office staff to coordinate RAQ & blood sample collection  Determination of HSV-2 antibody status via collection of subject blood sample and analysis by central lab (FOCUS HerpeSelect 2 ELISA IgG kit)  Educational material regarding genital herpes offered to all subjects

54. 53 Assessments / Procedures  Questionnaire administered in an area conducive to privacy for the patient  Duplicate random numbers applied to each subject’s blood sample & questionnaire, thus linking the blood sample to the RAQ  Identity of the subject will not be compromised; no subject names on questionnaire or blood sample  Conduct of study is not to interfere with patient care  One venipuncture if at all possible

55. 54 Risk Assessment Questionnaire  8 demographic questions  21 questions (symptoms/sexual behavior- attitudes)  14 optional questions (knowledge/beliefs re: STDs)  Self-administered via ACASI technology (Audio Computer-Assisted Self-Interviewing)

56. 55 How to Reach Me Douglas T. Fleming, MD Senior Researcher Mathematica Policy Research, Inc. PO Box 2393 600 Alexander Park Princeton, NJ 08543 Tel. (609) 936-2713 Fax (609) 799-0005 DFleming@Mathematica-MPR.com Our Web site: www.mathematica-mpr.com