Sexually Transmitted Diseases:
Sex With Women as a Risk Factor for Herpes Simplex Virus Type 2 Among Young Men Who Have Sex With Men in Baltimore
Mark, Hayley D. PhD, MPH, RN*; Sifakis, Frangiscos PhD, MPH†; Hylton, John B. PhD, MHS†; Celentano, David D. ScD,MHS†; MacKellar, Duncan A. MA, MPH‡; Valleroy, Linda A. PhD‡; Zenilman, Jonathan MD§
From the *Johns Hopkins University School of Nursing, †Johns Hopkins University Bloomberg School of Public Health, ‡Centers for Disease Control and Prevention; and the §Johns Hopkins University School of Medicine
We would like to thank the participants who enrolled in our study. We would also like to thank the dedicated staff who made the project a success, including Terrrence Precord, Supriya Mehta, Marshall Gold, Charmaine Nalty, James Drummond, William Edgar, Sean LeSane, Andrea Kehne, Mathew Woolf, Karen Yen Hobelmann, McCay Moiforay, Scott Wilfond, Ellen Taylor, Karen Eckert, Nicole Carpenetti, Greg Farina, James Narer, and Christopher Mast.
This work was supported by CDC cooperative agreement 062/CCU306213-06. Dr. Mark was an STD prevention postdoctoral fellow funded by the Association of Teachers of Preventive Medicine and the Centers for Disease Control and Prevention. Dr. Zenilman was supported by NIH award K24AI01633.
Correspondence: Hayley Mark, PhD, JHU School of Nursing, 525 N. Wolfe Street, Baltimore, MD 21205. E-mail: email@example.com.
Received for publication January 26, 2005, and accepted April 4, 2005.
Background: Herpes simplex virus type 2 is common among MSM and is a risk factor for transmission of HIV. The findings of studies investigating the relationship between infection with HSV-2 and number of sex partners among MSM are inconsistent and rarely distinguish between male and female partners.
Goal: To determine the prevalence and risk factors for infection with HSV-2, including the number and gender of sex partners, in a group of MSM in Baltimore, MD.
Study: This was a cross-sectional study among young MSM in Baltimore.
Results: Of the blood samples from 824 participants, 19.3% had HSV-2 antibodies. After adjusting for known HSV-2 correlates, independent predictors of HSV-2 seropositivity included HIV seropositivity, black race, older age, number of lifetime female sex partners, recent unprotected receptive anal intercourse with a man.
Conclusions: This study suggests that female sex partners may be an important source of HSV-2 infection among young bisexual MSM. After adjusting for known HSV-2 correlates, the number of lifetime female but not male sex partners was independently associated with HSV-2. These results highlight the need for HSV-2 prevention and treatment efforts targeting MSM who also have sex with women. Future investigations of HSV-2 and sexual behavior among MSM need to distinguish between male and female sex partners.
HERPES SIMPLEX VIRUS TYPE 2 (HSV-2) is the most common cause of genital ulcer disease in the United States and an important determinant of sexual transmission of human immunodeficiency virus (HIV).1–8 Several studies of HSV-2 have identified male-to-male sex and/or self-reported homosexuality as a risk factor for HSV-2 infection.9–13 Among men who have sex with men (MSM), prevalence of HSV-2 infection has varied from 20% to 35% among HIV-negative men and up to 66% among HIV-infected men.14,15
Previous studies of HSV-2 among MSM have reported associations between HSV-2 and HIV infections,13,14,16 previous STD,13,16 concurrent HSV-1 infection,16 and injection drug use.12 The relationship between the number of sex partners and HSV-2 infection among MSM is unclear. Studies in Amsterdam, for example, found an independent association between increasing numbers of lifetime sex partners and HSV-2 among MSM.11,16 Studies of MSM in San Francisco and Melbourne, Australia, however, found no relationship between the number of sex partners and HSV-2 infection.13,14 Although Siegel et al.12 found that number of lifetime male sexual partners was associated with HSV-2 infection among HIV-infected MSM in San Francisco, this association was not found among MSM who were HIV negative. One potential explanation for these inconsistent findings is that the studies failed to evaluate the role of female sex partners as a source of HSV-2 infection among MSM. Many MSM also have sex with women.17–20 Montgomery et al.,17 for example, found that of 5156 HIV-infected MSM, 34% of black, 26% of Hispanic, and 13% of the white participants reported having sex with a woman in the last 5 years. Others have found that bisexual men are more likely to have unprotected sex with female partners than with male partners.12,21 Because HSV-2 infection is prevalent among women in the United States, MSM may be at risk for HSV-2 from female sexual partners.
Given the high incidence of HIV among MSM, the link between HSV-2 infection and HIV transmission, and that many MSM are bisexual, investigations of MSM that distinguish between male and female sexual partners are warranted. In this paper, we evaluate whether, after adjusting for the effects of known correlates of HSV-2 infection, the association between HSV-2 infection and number of sexual partners among MSM depends on partner gender.
Materials and Methods
The Young Men’s Survey (YMS) study design, sampling, and data collection procedures have been described elsewhere in detail.19,20 In summary, YMS was a 2-phase, cross-sectional, anonymous survey of men who attended MSM-identified public venues in Baltimore, MD; Dallas, TX; Los Angeles, CA; Miami, FL; New York, NY; and Seattle, WA. This paper uses only the data from men recruited at the Baltimore site. Baltimore was the only site that collected HSV-2 data on subjects. Identical methods were used in each phase, with the exception that men 15 to 22 years of age were recruited in phase I (1994–1998), and men 23 to 29 years of age were recruited in phase II (1998–2000). Venues were identified from advertisements, individual and group interviews, and field observations. Sampling frames were then constructed of those venues and daytime periods where a minimum of 7 eligible men (determined by age and residence) might be encountered during a 4-hour sampling event.
Each month, 12 or more venues and their associated daytime periods were randomly selected from updated sampling frames. These venues and periods were then scheduled for sampling in the upcoming month. During sampling events, recruiters consecutively approached men who appeared under 30 years of age and asked if they would participate in a brief eligibility interview. Eligibility criteria for the Baltimore study site included Baltimore City residence, age less than 30 years, and no prior participation in the current research phase.
In a nearby van or office location, trained interviewers obtained informed consent from participants, administered a standard questionnaire, conducted prevention counseling, and obtained blood specimens for HIV and HSV-2 testing. Participants were reimbursed $40 (phase I) to $50 (phase II) for their time and were scheduled to receive their test results within 2 weeks. Participants who returned for their test results were provided risk-reduction counseling and referrals for health care as needed. Finally, antibody-profile assays were used to test specimens of suspected duplicate participants.22 When antibody profiles matched, only data from the first interview and specimen were analyzed. The YMS protocol was approved by institutional review boards at the CDC and at state and local institutions that conducted the survey.
The current analysis was restricted to men from the Baltimore site (n = 939), who reported sex with a man at least once in a lifetime (n = 843) and for whom HSV-2 test results were available (n = 824).
A standard questionnaire was used in each phase but was modified between phases. Identical or nearly identical measures were used for both phases. Both questionnaires included questions on demographic characteristics, sexual behavior, and illicit drug use. For many behavioral questions, a 6-month recall period was used.
In our analysis, we focused on variables that had been previously identified in the literature as correlates of HSV-2 infection among MSM or heterosexuals. Variables investigated included race/ethnicity, age, HIV infection, lifetime number of sexual partners (male and female), cocaine use (lifetime use and use during sex in the past 6 months), syringe use (lifetime use and use during sex in the past 6 months) unprotected oral and anal (receptive and insertive) sex with a man in the past 6 months, and unprotected vaginal and anal intercourse with a woman in the past 6 months. Data from 3 continuous variables, age and number of male and female partners, were divided into 3 nearly equal categories. Number of male and female partners was assessed by the questions: During your lifetime, with how many males have you had sex? and During your lifetime, with how many females have you had sex? Because few participants reported being Asian or Hispanic, we collapsed racial categories into white (n = 462), black (n = 303), and other (n = 95). Lifetime cocaine use was assessed by the question, Have you ever used cocaine? Cocaine use during sex in the past 6 months was measured by the question, Were you high or buzzed on cocaine during sex in the past 6 months? Lifetime syringe or other injection equipment use was determined by the question: In your lifetime, have you ever used needles or “works” to shoot drugs, including steroids and hormones, that were not prescribed by a medical person?
Specimens were tested for HIV and HSV-2 at local laboratories with assays licensed by the US Food and Drug Administration. Stored serum samples were tested for HSV-2 by the Focus Technologies HerpeSelect Type 1 and Type 2 ELISA assays. The HerpeSelect assays use purified HSV recombinant gG1 and gG2 antigens immobilized on polystyrene microwells for the detection of HSV-1 and HSV-2 serum antibodies. All testing was performed in accordance with the manufacturer’s guidelines, with 10% of all specimens retested for quality assurance.
Associations between HSV-2 seropositivity and independent variables were characterized by χ2 tests and logistic regression. Logistic regression analysis was used to identify multivariate predictors of HSV-2 seropositivity. The multivariate model included all variables significant at p <0.05 in univariate analysis. All statistics were computed using the Statistical Program for Social Sciences Version 10.0 (SPSS).
Baltimore YMS phase I data collection began in May 1996 and was completed in April, 1998. Phase II data collection began in September 1998 and concluded in December 2000. During 435 sampling events in Baltimore, YMS staff obtained eligibility data on 7263 (85%) of 8556 men who appeared to be age eligible. Of these, 2063 (28%) met age and residence eligibility requirements for study participation, including 449 men who had been approached previously, yielding 1614 unique eligible men. Of these eligible men, 939 (58%) were enrolled in the study. Participants who reported no male sexual partners in their lifetime or did not have HSV-2 results (n = 115) were excluded from this analysis.
Select demographic and risk characteristics of the 824 MSM are shown in Table 1. The median age of the study population was 23 years; 77% reported their sexual identity as gay, 20% as bisexual, and 3% as straight; and 66% reported at least 1 lifetime female sex partner. Forty-eight percent of black participants reported more than 3 lifetime female sexual partners compared with 36% of white participants. The median number of lifetime male sex partners was 10, and the median number of lifetime female sex partners was 2. In the 6 months before their interview, 92% reported unprotected oral sex with a man, 52% reported unprotected anal intercourse (receptive or insertive) with a man, and 28% reported unprotected receptive anal intercourse (URAI).
Univariate Risk Factors for HSV-2 Infection
One hundred fifty-nine (19.3%) MSM tested positive for HSV-2 antibody. Age, race, HIV status, lifetime number of female and male sexual partners, and unprotected receptive anal sex with a man were univariately associated (P <0.05) with HSV-2 infection (Table 1). There was no statistically significant association between HSV-2 infection and unprotected oral sex or insertive anal sex with a man in the past 6 months or unprotected vaginal or anal intercourse with a woman in the past 6 months. Also, lifetime cocaine use, cocaine use during sex in the past 6 months, or lifetime use of a syringe or works was not significantly associated with HSV-2 infection (Table 1).
Independent Risk Factors for HSV-2 Antibodies
In a multivariate logistic regression model, HIV serostatus, 3 or more lifetime female sexual partners, black race, older age, and recent unprotected receptive anal intercourse with a man remained independent correlates of HSV-2 infection (Table 1). Lifetime number of male sex partners did not remain significantly associated with HSV-2 infection.
To our knowledge, this is the first report suggesting that female sex partners may be an important source of HSV-2 infection among young bisexual MSM. Twenty-seven percent of the men with 3 or more lifetime female sexual partners tested positive for HSV-2. In comparison, 25% of the men with 20 or more lifetime male sexual partners tested HSV-2 seropositive. After adjusting for known HSV-2 correlates, the number of lifetime female but not male sex partners was independently associated with HSV-2.
This finding may reflect the epidemiology of HSV-2 among women, as well as sexual behavior among bisexual men. The NHANES-III, a national seroprevalence study, reported a seroprevalence rate for HSV-2 antibodies of 20% for white women and over 50% for black women (compared with HSV-2 antibody prevalence of 12% and 30% among white and black MSM, respectively, in our study). Thus, prevalence of HSV-2 infection may be higher among female partners than male partners of bisexual men. Potentially higher infection prevalence among female partners, combined with evidence that bisexual men are less likely to have protected sex with female than male partners,23 may lead to higher HSV-2 transmission rates to bisexual men from female versus male sexual partners.
The prevalence of HSV-2 infection in this study (19.3%) was lower than that of other studies among MSM. This could be a result of the younger age on average of this sample compared to other investigations as seroprevalence rates of HSV-2 increase with age. However, estimates of HSV-2 infection from previous investigations may be higher because their samples were drawn from MSM seeking HIV/STD diagnostic or treatment services and not limited to younger age groups.10,11,13–15 Our sample may be more representative of men age 15 to 29 from the general MSM population than samples from clinic-based surveys.
The prevalence of HSV-2 found in this study is a conservative estimate of the actual rate of genital herpes infections in the sample. Genital herpes infections are caused by both herpes simplex 1 (HSV-1) and HSV-2. A recent study of the etiology of genital and anal lesions among a group of homosexual men recruited from a sexually transmitted disease clinic found that 47% of the lesions were due to HSV-1.24
Four other variables were independently associated with HSV-2 infection: HIV-positive serostatus, black race, recent unprotected anal intercourse with a man, and older age (>25 years). Consistent with over 20 studies that have found HSV-2 infection to be a risk factor for HIV acquisition, HIV infection was an independent predictor of HSV-2 in this analysis.10,12 HIV-positive men in this study were almost 4 times as likely to be HSV-2 seropositive as HIV-negative men. Currently, clinical trials are under way to determine the efficacy of HSV-2 suppression with daily antiviral medications on HIV acquisition.25 Our findings underscore the importance of this research and other interventions aimed to reduce HSV-2 acquisition and/or suppress reactivation.
High prevalence of HSV-2 infection in the black community has been noted previously.26–29 In our study, the disparity in HSV-2 infection by race is also striking. Even when adjusting for age, number of partners, and HIV status, the odds of having HSV-2 are more than 2 times greater for blacks than whites. Nationally, rates of HSV-2 are higher among blacks than whites, and blacks most frequently choose sexual partners who are also black (assortative mating).30 Thus, blacks are more likely to have a partner with HSV-2 than if the mixing patterns were more heterogeneous. Black participants in this study were also more likely than white MSM to have both male and female sexual partners, and HSV-2 is more prevalent among women than men.23 The combination of high baseline prevalence, assortative mixing patterns, and having female as well as male partners likely contribute to the higher prevalence rate of HSV-2 among blacks in this study. The finding that HSV-2 seroprevalence was higher among older men likely reflects the increased probability of acquiring HSV-2 infection with increased duration of exposure.3,4
The current study has several limitations. First, the study uses a cross-sectional design and thus, causality cannot be inferred. However, the central questions of this study do not rely on causal models, but instead examine associations among variables. Another limitation is that the data are self-reported by participants. It is possible that social desirability may have influenced respondents’ answers to sensitive questions, such as condom use. Evidence suggests, however, that well-designed questionnaires can provide acceptable data when administered appropriately.31 The findings of this study are generalizable only to the population of young MSM who attend MSM-identified venues in Baltimore. In spite of these limitations, YMS sampled a large and diverse population of young MSM and the majority of young MSM within a community probably attend 1 or more public venues included in YMS sampling frames within a survey year.32 Finally, this study is a secondary analysis of existing data; thus, we were unable to evaluate certain risks, such as history of a STD other than HSV-2, whether a participant had ever had a sex partner with genital herpes, or whether a participant had experienced genital sores or blisters.
This study found that in a group of MSM, number of female partners was associated with HSV-2 infection. Additional investigations to determine if this relationship occurs in other populations of MSM are warranted. Future investigations of HSV-2 and sexual behavior among MSM need to distinguish between male and female sex partners in order to clarify this issue. Much attention has been given to the risk of HIV acquisition among women who have sex with bisexual men.17,18,33–36 Our results suggest that bisexual men may be at risk for contracting HSV-2 from women. Given the increased risk of acquiring and transmitting HIV if infected with HSV-2, these findings are particularly important for MSM. Information on the risks of sex with female partners should be included in HIV prevention information for MSM, and there is a need to affirm safer sex practices with partners of both genders among bisexual men.
1. Corey L, Handsfield H. Genital herpes and public health: addressing a global problem. JAMA 2000; 283:791–794.
2. Corey L, Wald A. Genital herpes. In: Holmes K, Nardh P, Wasserheit J, eds. Sexually Transmitted Diseases. 3rd ed. New York: McGraw-Hill, 1999:285–312.
3. Reynolds S, Risbud A, Shepherd M. Recent herpes simplex virus type 2 infection and the risk of human immunodeficiency virus type 1 acquisition in India. J Infect Dis 2003; 187:1513–1521.
4. Renzi C, Douglas JM, Foster M, et al. Herpes simplex virus type 2 infection as a risk factor for human immunodeficiency virus acquisition in men who have sex with men. J Infect Dis 2003; 187:19–25.
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 2002; 185:45–52.
6. Keet IP, Lee FK, van Griensven GJ, et al. Herpes simplex virus type 2 another genital ulcerative infections as a risk factor for HIV-1 acquisition. Genitourin Med 1990; 66:330–333.
7. Serwadda D, Gray RH, Sewankambo, et al. Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case control study in Rakai, Uganda. J Infect Dis 2003; 10:1492–1497.
8. Schacker T, Ryncarz AJ, Goddard J, et al. Frequent recovery of HIV-1 from genital herpes simplex lesions in HIV-1 infected men. JAMA 1998; 280:61–66.
9. Cowan FM, Johnson AM, Ashley R, et al. Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations. BMJ 1994; 309:1325–1329.
10. Suligoi B, Dorrucci M, Volpi A, et al. Prevalence and determinants of herpes simplex type 2 infection in a cohort of HIV-positive individuals in Italy. Sex Transm Dis 2002; 29:665–667.
11. Van de Laar MJW, Termorshyizen F, Slomka MJ et al. Prevalence and correlates of herpes simplex virus type 2 infection: evaluation of behavioural risk factors. Int J Epidemiol 1998; 27:127–134.
12. Siegel D, Golden E, Washington AE, et al. Prevalence and correlates of herpes simplex infections: the population-based AIDS in multiethnic neighborhoods study. JAMA 1992; 268:1702–1708.
13. Turner KR, McFarland W, Kellogg, et al. Incidence and prevalence of herpes simplex virus type 2 infection in persons seeking repeat HIV counseling and testing. Sex Transm Dis 2003; 30:331–334.
14. Stamm WE, Handsfield H, Rompalo AM, et al. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA 1998; 260:1429–1433.
15. Russell DB, Tabrizi SN, Russell JM, et al. Seroprevalence of herpes simplex types 1 and 2 in HIV-infected and uninfected homosexual men in a primary care setting. J Clin Virol 2001; 22:305–313.
16. Dukers NH, Bruisten SM, van den Hoek JA, et al. Strong decline in herpes simplex virus antibodies over time among young homosexual men is associated with changing sexual behavior. Am J Epidemiol 2000; 152:666–673.
17. Montgomery JP, Mokitoff ED, Gentry AC, et al. The extent of bisexual behaviour in HIV-infected men and implications for transmission to their female sex partners. AIDS Care 2003; 15:829–837.
18. Wold C, Seage GR 3rd, Lenderking WR, et al. Unsafe sex in men who have sex with both men and women. J Acquir Immun Defic Syndr Hum Retrovirol 1998; 17:371–377.
19. MacKellar DA, Valleroy LA, Karon JM, et al. The young men’s survey: methods for estimating HIV seroprevalence and risk factors among young men who have sex with men. Public Health Rep 1996; 111(suppl 1):138–144.
20. Valleroy LA, MacKellar DA, Karon JM, et al. HIV prevalence and associated risks in young men who have sex with men. JAMA 2000; 284:198–204.
21. Tabet S, Sanchez J, Lama J, et al. HIV, syphilis and heterosexual bridging among Peruvian men who have sex with men. AIDS 2002; 16:1271–1277.
22. Ascher DP, Roberts C. Determination of the etiology of seroconversion in HIV testing by antibody fingerprinting. J Acquir Immun Defic Syndr 1993; 6:241–244.
23. Fleming D, McQuillan G, Johnson R, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997; 337:1105–1111.
24. Lafferty WE, Downer L, Celum C, et al. Herpes simplex virus type 1 as a cause of genital herpes: impact on surveillance and prevention. J Infect Dis 2000; 181:1454–1457.
25. Celum CL, Robinson NJ, Cohen MS. Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection. J Infect Dis 2005; 191(suppl 1):S107–S114.
26. Johnson RE, Lee F, Hadgu A, et al. US genital herpes trends during the first decade of AIDS: prevalences increased in young whites and elevated in blacks. Sex Transm Dis 21(suppl): S109.
27. Gibson J, Hornung CA, Alexander G, et al. A cross-sectional study of herpes simplex virus types 1 and 2 in college students: occurrences and determinants of infection. J Infect Dis 1990; 162:306–312.
28. Sucato G, Celum C, Dithmer D, et al. Demographic rather than behavioral risk factors predict herpes simplex virus type 2 in sexually active adolescents. Pediatr Infect Dis 2001; 20:422–426.
29. Wald A, Koutskey L, Ashley R, et al. Genital herpes in a primary care clinic: demographic and sexual correlates of herpes simplex type 2 infections. Sex Transm Dis 1997; 24:149–155.
30. Laumann E, Youm Y. Racial/ethnic group differences in the prevalence of sexually transmitted disease in the United States: a network explanation. Sex Transm Dis 1999; 26:250–261.
31. Weinhardt LS, Forsyth AD, Carey MP, et al. Reliability and validity of self-report measures of HIV-related sexual behavior. Arch Sex Behav 1998; 27:155–180.
32. Lemp GF, Hirozawa AM, Givertz D, et al. Seroprevalence of HIV and risk behaviors among young homosexual and bisexual men. JAMA 1994; 272:449–454.
33. Chu S, Peterman TA, Doll L, et al. AIDS in bisexual men in the United States: epidemiology and transmission to women. Am J Public Health 1992; 82:220–224.
34. Doll L, Beeker C. Male bisexual behavior and HIV risk in the United States: synthesis of research with implications for behavioral interventions. AIDS Educ Prev 1996; 8:205–225.
35. Ekstrand ML, Coates TJ, Guydish JR, et al. Are bisexually identified men in San Francisco a common vector for spreading HIV infection to women? Am J Public Health 1994; 84:915–919.
36. Kalichman S, Roffman R, Picciano J, et al. Risk for HIV infection among bisexual men seeking HIV-prevention services and risks posed to their female partners. Health Psychol 1998; 17:320–327.
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