Abstract

The seroprevalence of herpes simplex virus type 2 (HSV-2) infection was studied among 4128 patients from sexually transmitted disease (STD) clinics who were enrolled in a randomized controlled trial of human immunodeficiency virus and STD counseling efficacy. HSV-2 seroprevalence was 40.8% and was higher in women than in men (52.0% vs. 32.4%; P<.0001) and higher in blacks than in nonblacks (48.1% vs. 29.6%; P<.0001). Among 14–19-year-old patients, 36.8% of black women and 25.8% of nonblack women were infected with HSV-2. Independent predictors of HSV-2 seropositivity included female sex, black race, older age, less education, more lifetime sex partners, prior diagnosis of syphilis or gonorrhea, and lack of HSV-1 antibody. The majority of HSV-2–seropositive persons (84.7%) had never received a diagnosis of genital herpes. HSV-2 infection is common in STD clinic attendees in the United States, even among young age groups, especially among women. Efforts to prevent genital herpes should begin at an early age. The high rate of undiagnosed HSV-2 infection likely contributes to ongoing transmission

Herpes simplex virus type 2 (HSV-2) is the main cause of genital herpes and a leading cause of genital ulcer disease throughout the world [1, 2]. Although HSV-2 may cause painful genital blisters and ulcerations, most HSV-2 infections are unrecognized or asymptomatic [3–5] yet can still be transmitted to a sex partner [4]. Furthermore, there is mounting evidence that HSV-2 facilitates the transmission of human immunodeficiency virus (HIV) infection [6, 7]. In the United States, large national surveys such as the National Health and Nutrition Examination Surveys (NHANES) II and III have shown that the prevalence of HSV-2 antibody in the general US population has increased since 1978, with 22% of US adults being infected by the early 1990s [8]. However, in high-risk settings such as sexually transmitted disease (STD) clinics, where patients are more likely than the general population to be at risk of both HSV-2 and HIV infection, HSV-2 prevalence data are less complete. Most large HSV-2 seroprevalence studies in STD clinics have been performed outside the United States [9–11] or primarily among US women [5, 12]. Project RESPECT was a large randomized controlled trial in 5 urban STD clinics, which demonstrated that HIV and STD risk-reduction counseling can result in behavioral change and the prevention of new bacterial STDs [13]. The purpose of the present study was to use enrollment data from Project RESPECT to determine the seroprevalence and correlates of HSV-2 infection in a geographically dispersed population of US STD clinic patients

Methods

Study design and procedures.We performed a cross-sectional seroprevalence analysis, using questionnaire data and serum samples obtained during the Project RESPECT enrollment visit. The complete methodology for Project RESPECT has been described in detail elsewhere [13]. In brief, the trial was conducted from July 1993 through September 1996, at public, inner-city STD clinics in Baltimore, Denver, Long Beach, Newark, and San Francisco. All English-speaking patients aged ⩾14 years who came for STD examinations during the study period and had had vaginal intercourse in the preceding 3 months were asked to participate in the study. Men who identified themselves as homosexual or who had had a male sex partner during the preceding 12 months were excluded from the study, as were those patients found to be HIV positive at enrollment. Participants were then randomized to 4 arms with varying intensities of safer-sex counseling. Participants in arms 1–3 were scheduled for quarterly follow-up visits over the next 12 months; arm 4 participants had no routine follow-up scheduled. Unlike participants in the first 3 arms, arm 4 participants did not consistently undergo serum testing for HSV-2 at baseline enrollment and thus were excluded from this seroprevalence analysis

At the enrollment visit, participants were interviewed to obtain information on sociodemographic characteristics, sexual history and behavior, and STD history, including the question “Have you ever been told by a doctor or nurse that you had genital herpes?” No data were available on previous symptoms suggestive of genital HSV (e.g., undiagnosed genital blisters or ulcerations) or contact with a sex partner known to have genital herpes. Genital examinations and laboratory testing for STDs were performed for all patients and included serologic testing for HSV-1 and HSV-2

Laboratory methods.Stored serum samples were tested for antibodies to HSV-1 and HSV-2 by a type-specific strip immunoblot assay (Chiron) based on recombinant antigen bands for glycoproteins gB1, gD2, gG1, and gG2 [14]. The sensitivity of the strip immunoblot assay has been found to be >98% for HSV-2 and 95% for HSV-1, with a specificity of >99% for both, compared with Western blot analysis [15]. All tests were performed in the same laboratory, with the manufacturer's automated processor. For patients with symptoms or signs of genital herpes, a diagnosis of primary or recurrent infection was made in each STD clinic, on the basis of the examiner's clinical impression of the patient's history and physical condition, without the standardized use of confirmatory HSV culture or other virologic testing. Infection with Neisseria gonorrhoeae was defined as a positive culture or, for men, as gram-negative intracellular diplococci on a Gram stain of a urethral swab. Infection with Chlamydia trachomatis was defined as a positive result of polymerase chain-reaction assay on endocervical swabs (women) and urine samples (men). Syphilis was diagnosed by positive treponemal and nontreponemal antibody tests. Infection with Trichomonas vaginalis in women was defined by a positive culture result or by trichomonads seen on a wet mount from a vaginal swab

Statistical analysis.Point prevalences, 95% confidence intervals (CIs), and odds ratios (ORs) were calculated by SAS software, version 6.12 (SAS Institute). Univariate and bivariate analyses were performed to examine the association between HSV-2 seropositivity and demographic, sexual behavior, and current and past STD variables by the χ2 test (P<.05). Multiple logistic regression was used to determine independent predictors of HSV-2 seropositivity, by a manual backward-elimination process. All demographic, sexual-behavior, and STD variables with crude associations at P<.20 were first entered into a model. A manual stepwise process then removed nonsignificant variables that were not significant confounders, according to the likelihood ratio test using the χ2 distribution for significance (>95%). Independent predictors in the final model were retained variables with a significance level of P<.05. Separate models for men and women were used to assess variables obtained for only 1 sex. An additional multiple logistic regression model was created in the same fashion among only HSV-2–seropositive persons to determine independent predictors of remaining undiagnosed with genital herpes despite having HSV-2 antibodies

Results

From July 1993 through June 1995, 13,471 eligible patients were asked to participate in Project RESPECT, and 5833 (43%) agreed to enroll. Study participants and those who refused were similar in age, racial or ethnic background, and education level, although, compared with those who refused, participants were more likely to be women (OR, 1.49; 95% CI, 1.44–1.55), to have had an STD at enrollment (OR, 1.19; 95% CI, 1.14–1.24), and to have been previously tested for HIV (OR, 1.13; 95% CI, 1.08–1.18). After exclusion of patients with a positive baseline HIV test result (n=75) and of arm 4 participants who did not routinely receive HSV testing (n=1430), 4328 baseline enrollees remained for this seroprevalence analysis. HSV-2 test results were available for 4128 (95.4%) of these participants. Results were unavailable for 200 participants because of insufficient quantities of serum for HSV testing and the loss of serum samples during transportation, storage, or processing

Of 4128 total participants, 2348 (56.9%) were male and 1780 (43.1%) were female. The study population was 60.7% black, 20.6% white, 11.3% Hispanic, and 7.4% other racial or ethnic group. The median age was 25 years (range, 14–76 years). Study participants were predominantly low income, and fewer than one-third of respondents had an education beyond high school. All of the study participants had had at least 1 sex partner; the median number of lifetime sex partners was 10 for women and 20 for men. The median age at first sexual intercourse was 15 years. Almost two-thirds (62.7%) of subjects reported prior treatment for at least 1 STD, with gonorrhea being the most commonly reported past STD

Overall, 1686 (40.8%) of the 4128 participants were positive for HSV-2 antibody (table 1). HSV-2 seroprevalence was higher among women (52.0%) than among men (32.4%; P<.0001). HSV-2 seroprevalence among blacks was 48.1%, significantly higher than that among whites (30.1%; P<.0001). HSV-2 seroprevalence in Hispanics and other racial or ethnic groups did not differ significantly from that in whites. Black females had the highest overall seroprevalence, 62.8% (95% CI, 59.7–65.9), whereas black males had a seroprevalence of 39.0% (95% CI, 36.5–41.4), with very little variation by study site, for either black women (59%–68%) or black men (37%–42%). Similar to the frequency seen in black males, 40.8% (95% CI, 36.0–41.0) of white females were HSV-2 seropositive, whereas white males had the lowest overall seroprevalence, at 19.7% (95% CI, 15.9–23.6). HSV-2 seroprevalence increased with older age and with less education. Seroprevalence was lowest in San Francisco (33.2%) and highest in Baltimore (50.1%), with differences largely attributable to the proportion of black participants at each study site

Table 1

Herpes simplex virus type 2 (HSV-2) seroprevalence, by selected participant characteristics

Table 1

Herpes simplex virus type 2 (HSV-2) seroprevalence, by selected participant characteristics

Figure 1 shows HSV-2 seroprevalence, by age, for black and nonblack males and females. Whites, Hispanics, and other races or ethnicities were grouped as nonblacks, because they were not significantly different from each other. HSV-2 seroprevalence increased with age, for all sex and racial groups (χ2 for trend, P<.0001 for all groups). For each age group, women had higher seroprevalence rates than did men, and blacks had higher rates than did nonblacks (P<.05 for each comparison). Within each racial group, women often had higher rates of HSV-2 infection than did substantially older men. For example, nonblack women aged 14–19 years had a higher HSV-2 seroprevalence than did nonblack men aged 25–29 years, and black women aged 20–24 years had a higher rate than did black men aged 30–39 years. Even in the youngest age group (14–19 years old), 25.8% of nonblack women and 36.8% of black women were already infected with HSV-2. It was difficult to determine the age at which HSV-2 seroprevalence first started to increase, because the small number of study participants <17 years old made estimates of seroprevalence during these early adolescent years unreliable. However, among 91 females who were 17 years old, the HSV-2 seroprevalence was already 33.0% (95% CI, 22.8–43.2). In the oldest age group (⩾40 years old), ∼50% of nonblack males, 65% of black males, 60% of nonblack females, and almost 90% of black females had HSV-2 infection

Figure 1

Herpes simplex virus type 2 (HSV-2) seroprevalence according to age, race, and sex. HSV-2 seroprevalence increased with age (χ2 for trend, P<.0001 for all race and sex groups). For each age group, women had higher seroprevalences than did men, and blacks had higher rates than nonblacks (P<.05 for all comparisons)

Figure 1

Herpes simplex virus type 2 (HSV-2) seroprevalence according to age, race, and sex. HSV-2 seroprevalence increased with age (χ2 for trend, P<.0001 for all race and sex groups). For each age group, women had higher seroprevalences than did men, and blacks had higher rates than nonblacks (P<.05 for all comparisons)

Sexual-behavior history and past STD history also were associated with HSV-2 seroprevalence (table 1). On univariate analysis, an earlier age at first sexual intercourse was associated with higher seroprevalence rates. The presence of HSV-2 antibody also increased with increasing numbers of lifetime sex partners (χ2 for trend, P<.0001). There were 234 persons who had been given a clinical diagnosis of herpes in the past, of whom 197 (84.2%) had HSV-2 antibodies. Of the 37 persons with a prior herpes diagnosis who lacked HSV-2 antibodies, 29 had HSV-1 antibodies and 8 did not. A prior diagnosis of gonorrhea, chlamydial infection, syphilis, and trichomoniasis (for women) were all associated with HSV-2 infection. Among these past STDs, HSV-2 seroprevalence was highest in participants with a prior diagnosis of syphilis (71.0%) and in women with prior trichomoniasis (74.4%). HSV-2 seroprevalence was slightly higher in those who were positive for HSV-1 antibody (42.0%) than in those who were not (37.9%). Likewise, men who were uncircumcised were slightly more likely to be HSV-2 infected than were those who were circumcised (36.4% vs. 30.8%)

Figure 2 demonstrates HSV-2 seroprevalence according to number of lifetime sex partners, race, and sex. HSV-2 seroprevalence increased with increasing numbers of lifetime sex partners, for all sex and racial groupings (χ2 for trend, P<.0001 for all groups). For each category of lifetime sex partners, women had higher prevalences than did men (P<.0001) and blacks had higher rates than did nonblacks (P<.05). Black women had the lowest median number of lifetime sex partners (8) but had the highest overall seroprevalence. Even among black women with only 1–5 lifetime sex partners, HSV-2 seroprevalence was 45.7% (95% CI, 40.1–51.1). Among nonblack women with only 1–5 lifetime sex partners, HSV-2 seroprevalence was 24.7% (95% CI, 18.8–30.5). In fact, even with only 1 or 2 lifetime partners, HSV-2 seroprevalence was 33.9% (95% CI, 21.3–46.5) among black women and 17.7% (95% CI, 7.4–28.1) among nonblack women

Figure 2

Herpes simplex virus type 2 (HSV-2) seroprevalence by lifetime sex partners, race, and sex. HSV-2 seroprevalence increased with increasing numbers of lifetime partners (χ2 for trend, P<.0001 for all race and sex groups). For each category of lifetime partners, women had higher seroprevalences than did men, and blacks had higher rates than nonblacks (P<.05 for each comparison)

Figure 2

Herpes simplex virus type 2 (HSV-2) seroprevalence by lifetime sex partners, race, and sex. HSV-2 seroprevalence increased with increasing numbers of lifetime partners (χ2 for trend, P<.0001 for all race and sex groups). For each category of lifetime partners, women had higher seroprevalences than did men, and blacks had higher rates than nonblacks (P<.05 for each comparison)

Independent predictors of HSV-2 seropositivity, by multiple-logistic-regression analysis, are shown in table 2. After adjustment for other risk factors, women had >4 times the odds of HSV-2 infection that men had (OR, 4.6; 95% CI, 3.8–5.5). Black race was also independently associated with HSV-2, with an overall adjusted OR of 2.5 (95% CI, 2.0–3.2), compared with whites. The odds of HSV-2 also increased with increasing age and numbers of lifetime sex partners. Other independent predictors of HSV-2 seropositivity included less education, a history of gonorrhea, a history of syphilis, and fewer new sex partners in the past 3 months. It is noteworthy that, after we controlled for other risk factors, the relationship between HSV-1 antibody and HSV-2 changed, resulting in an inverse association (OR, 0.8; 95% CI, 0.7–0.9). Furthermore, in multivariate analysis, both age at first sex and study site were no longer independently associated with HSV-2 infection

Table 2

Independent predictors of herpes simplex virus type 2 (HSV-2) seropositivity, by multivariate analysis

Table 2

Independent predictors of herpes simplex virus type 2 (HSV-2) seropositivity, by multivariate analysis

Several variables were available only for women or only for men. When these were considered in separate models for women and men, 4 additional factors predicted HSV-2 infection in women: a prior diagnosis of trichomoniasis (OR, 1.6; 95% CI, 1.2–2.2), a current diagnosis of trichomoniasis (OR, 1.5; 95% CI, 1.1–2.2), a history of prostitution (OR, 1.9; 95% CI, 1.2–2.9), and having had a sex partner who had been in jail (OR, 1.3; 95% CI, 1.0–1.7). The only additional factor predicting HSV-2 infection in men was a history of being in jail (OR, 1.3; 95% CI, 1.0–1.6). It is noteworthy that circumcision was not independently associated with HSV-2 infection, after adjustment for other factors

Of the 1686 participants with HSV-2 antibodies, only 197 (11.7%) had been previously given the diagnosis of genital herpes, and an additional 60 (3.6%) were diagnosed clinically as having genital herpes during the enrollment visit. Thus, 84.7% of all HSV-2–infected persons remained undiagnosed at the end of the enrollment visit. By univariate analysis, race or ethnicity and HSV-1 status were most strongly associated with having undiagnosed HSV-2 infection. Among those with HSV-2 infection, blacks were significantly more likely than whites to remain undiagnosed (88.8% vs. 74.3%; P<.001). Likewise, among HSV-2–infected persons, those who were HSV-1 seropositive were more likely to remain undiagnosed than were those who were HSV-1 seronegative (86.6% vs. 79.7%; P=.0005). Table 3 displays the results of a multivariate analysis of factors associated with remaining undiagnosed with genital herpes among HSV-2–infected persons. Factors independently associated with being undiagnosed included black race, female sex, older age, still being in school, attending the Newark clinic, a diagnosis of gonorrhea at enrollment, and being positive for HSV-1 antibody. Thus, black race, female sex, and older age were independently associated not only with HSV-2 seroprevalence but also with the likelihood of remaining undiagnosed with genital herpes once infected

Table 3

Independent predictors of remaining undiagnosed with genital herpes among herpes simplex virus type 2 (HSV-2)–seropositive persons (n=1686), by multivariate analysis

Table 3

Independent predictors of remaining undiagnosed with genital herpes among herpes simplex virus type 2 (HSV-2)–seropositive persons (n=1686), by multivariate analysis

If both overall HSV-2 seroprevalence and the proportion of infections that remain undiagnosed are taken into account, the percentage of the entire study population with undiagnosed HSV-2 infection can be calculated. This percentage represents the potential yield of serologic screening to detect clinically undiagnosed HSV-2 infection that would not otherwise be found and is shown in table 4, for various race, sex, and age groups. For example, the yield of screening would be >20% in nonblack men ⩾30 years old, black men and nonblack women ⩾20 years old, and black women of any age. Among black men and nonblack women ⩾40 years old, and among black women ⩾20 years old, the yield of screening would be >50%

Table 4

Percentage of total study population with undiagnosed herpes simplex virus type 2 (HSV-2) infection, found only by serologic tests, according to age, race, and sex

Table 4

Percentage of total study population with undiagnosed herpes simplex virus type 2 (HSV-2) infection, found only by serologic tests, according to age, race, and sex

Discussion

These data represent the largest evaluation, to date, of HSV-2 seroprevalence in men and women attending STD clinics. The overall seroprevalence of HSV-2 was 41% in this population, predictably higher than the 22% HSV-2 seroprevalence seen in the general US population in the most recent NHANES study [8]. Approximately half of the women and half of the blacks in this study were HSV-2–seropositive. HSV-2 seroprevalence among nonblacks was 20% in men and 39% in women, whereas that among blacks was 39% in men and 63% in women. These findings are consistent with prior studies of women attending US STD clinics [5, 12]; however, similar studies have not previously been performed in heterosexual males. Overall HSV-2 seroprevalence was higher than that previously seen among STD clinic attendees in Europe [9–11]

The disparity in HSV-2 infection by sex was striking; even after we adjusted for age, race or ethnicity, and number of lifetime sex partners, the odds of having HSV-2 infection were >4 times greater in women than in men. Likely contributing to this finding is the demonstrated higher efficiency of HSV-2 transmission from men to women, compared with that from women to men [16]. The larger exposed mucosal surface area in women, which may be more easily traumatized, could account for a large part of this difference in transmission [2]. However, lack of circumcision, an anatomic condition that increases mucosal surface area in men and that has been shown to increase the risk of HIV acquisition [17], was not associated with HSV-2 infection in a multivariate model. It has also been postulated [8] that high rates of HSV-2 among women may be partially explained by the fact that women are more likely to choose partners who are older than themselves [18] and who therefore have a greater risk of HSV-2 infection. However, we found that HSV-2 seroprevalence was generally higher among younger women than among considerably older men, indicating that choice of older male partners is unlikely to be the primary explanation for high rates of HSV-2 infection in women. For women in this study, the prevalence of HSV-2 was notably high even among adolescents and those with few lifetime sex partners. Thus, HSV-2 prevention strategies must start at an early age in populations with high rates of STD

A second noteworthy finding was the higher seroprevalence of HSV-2 among black men and women than among other racial or ethnic groups, even when we controlled for other demographic and sexual-behavior characteristics. For any given number of lifetime sex partners, the adjusted odds of having HSV-2 infection were 2.5 times higher in blacks than in whites. This observation supports the idea that, with respect to HSV-2, the pool of potential partners is different for blacks and whites and that sexual networks may play a critical role in determining an individual's STD risk [19, 20]. Because the prevalence of HSV-2 is higher in blacks, and because sex partnerships tend to develop among members of the same race or ethnic group [18], blacks are likely to have a higher risk of coming into contact with an infected partner with each new partnership. In addition, recent work has shown that blacks who have had only 1 partner in the past year are much more likely to choose partners who have had ⩾4 partners in the past year than are their white counterparts [19]. If replicated in other studies, this “dissortative” partner choice may be a major contributor to the high prevalence of HSV-2 in black STD clinic attendees

For both sexes, past sexual behavior and STD history were predictors of HSV-2 infection, especially the number of lifetime sex partners and a prior history of gonorrhea or syphilis, as were both prostitution and prior or current diagnosis of trichomoniasis in women. Of note, after adjustment for other characteristics, such as age and total numbers of lifetime sex partners, we did not find an association between age at first intercourse and HSV-2 infection. This observation is consistent with that found in the general US population [8] and may have programmatic implications in that STD prevention efforts aimed at delaying first coitus may ultimately have a limited impact on prevention of HSV-2 infection. The association between HSV-2 infection and past STDs, although likely reflective of unmeasured behavioral factors, raises the interesting question of a possible biologic interaction. For example, it is possible that STDs such as syphilis, gonorrhea, and trichomoniasis could be cofactors for HSV-2 shedding or susceptibility, just as they are suspected to be for HIV [21, 22]. Unfortunately, we could not assess the very important potential interaction between HIV and HSV-2, because HIV-positive persons were excluded from Project RESPECT. The inverse association between HSV-1 and HSV-2 antibodies after adjustment for demographic and sexual behavior characteristics also suggests a potential biologic interaction between HSV-1 and HSV-2 [1, 2]. In a cross-sectional study such as this one, the timing and rates of new HSV-1 and HSV-2 infections are not known; however, our data suggest that HSV-1 may partially protect against HSV-2 infection

As also was true in other studies [3–5, 8–11], the vast majority of our patients with HSV-2 infection (84.7%) had never been given a diagnosis of genital herpes, either previously or at the time of their enrollment visit. A prior diagnosis of herpes was based on the question “Have you ever been told by a doctor or nurse that you had genital herpes?” There may have been participants who suspected that they had genital herpes but who had never received a definitive diagnosis from a clinician. Thus, our estimates may be influenced by either access to health care or health care–seeking behavior and may underestimate the number of participants who were aware of having genital herpes. Indeed, it is possible that geographic variation in health care utilization might partially explain the association between remaining undiagnosed and 1 of the 5 sites (Newark) involved in the study. Nonetheless, lack of a definitive diagnosis for those who are infected and who may not take precautions to prevent transmission could contribute to ongoing spread of HSV-2 infection

Because of this issue, HSV-2 serologic screening of selected populations at risk for STD has been discussed as a potential prevention strategy [23, 24]. Studies have shown that the majority of patients with previously “asymptomatic” HSV-2 infection can be taught to subsequently recognize clinical outbreaks [3, 25]; thus, screening would increase the likelihood that many subclinically infected persons would come to recognize lesions. Such knowledge would allow infected persons to avoid intercourse when herpetic lesions were present, to decrease the chance of transmission [3]. In fact, preliminary data indicate that knowledge of genital herpes is associated with delayed transmission of HSV to a sex partner [26]. Avoiding sex when one is symptomatic might also lead to a reduction in HIV transmission efficiency [6, 7], another potential benefit of an HSV-2 screening program. Furthermore, because a recent study of HSV-2–discordant couples has shown for the first time that condoms can prevent transmission of genital herpes [27], knowledge of HSV-2 infection detected by serologic screening might also facilitate prevention of herpes transmission, by condom use, even without recognition of symptomatic lesions. Our data indicate that, at the very least, the yield of a screening program in identifying undiagnosed HSV-2 infection in STD clinics would be substantial. Moreover, given the associations between HSV-2 infection and black race, female sex, and older age, combined with the increased likelihood that these groups will remain undiagnosed when infected, it follows that the yield of serologic screening in a particular clinical setting would partially depend on patient demographics. However, the degree of benefit of serologic screening in terms of clinical care and prevention has not yet been quantified, and there are potential concerns about the psychosocial and economic impact of screening [28, 29]. Thus, the role that newly licensed type-specific HSV-2 serologic tests play in HSV-2 prevention efforts should continue to be evaluated, with a focus on populations at greatest risk of undiagnosed infection

The present study had several limitations. First, the study population consisted of selected patients, representing only 43% of those eligible, who enrolled in a randomized controlled trial conducted in 5 inner-city public clinics; thus, these findings may not be generalizable to all STD clinic patients. Second, the type-specific antibody test used in this analysis is no longer available, affecting the reproducibility of these findings in future seroprevalence studies. However, the sensitivity of the strip immunoblot assay for HSV-2 has been found to be >98%, and specificity >99%, compared with Western blot analysis [15]. Thus, our results are likely to be generally valid. Finally, this study was a secondary analysis of existing data and thus is not as strong as it would be if designed specifically to evaluate HSV-2 seroprevalence. Because it was a secondary analysis, we were unable to evaluate certain herpes-specific risks, such as whether a participant had ever had a sex partner with genital herpes or whether a participant had ever experienced genital sores or blisters

Despite these limitations, the data from this large evaluation offer observations that will be important for future prevention efforts. First, the high seroprevalence rates among women and blacks, even among adolescents and those with few lifetime sex partners, indicate that HSV-2 prevention efforts must begin during early adolescence, before presentation for STD-related concerns and, ideally, even before the onset of sexual activity. Second, the high seroprevalence among blacks, even after adjustment for lifetime sexual exposure, implies that HSV-2 transmission may be influenced as much by sexual-network dynamics as by individual risk behaviors, potentially limiting the impact of prevention approaches aimed at changing individual behavior. Finally, the high rate of undiagnosed HSV-2 infection in this population likely contributes to ongoing transmission, highlighting the need for further evaluation of the risks and benefits of HSV-2 serologic screening as a prevention strategy

Project RESPECT Study Group

Baltimore: Carolyn Erwin-Johnson, Andrew L. Lentz, Mary A. Staat, Dawn Sweet, Jonathan M. Zenilman (Principal Investigator [PI]). Denver: John M. Douglas (PI), Tamara Hoxworth, Ken Miller, William McGill. Long Beach: Ruth Bundy (co-PI), Laura A. Hoyt, C. Kevin Malotte, Fen Rhodes (PI). Newark: Michael Iatesta, Eileen Napolitano (co-PI), Judy Rogers, Ken Spitalny (PI). San Francisco: Gail A. Bolan (PI), Coleen LeDrew, Kimberly A. J. Coleman, Luna Hananel, Charlotte K. Kent. NOVA, Inc., Bethesda, Maryland: Robert Francis (PI), Christopher Gordon, Nancy Rosenshine (PI), Carmita Signes. Centers for Disease Control and Prevention: Sevgi Aral, Robert H. Byers, Beth Dillon, Martin Fishbein, Sandra Graziano, Mary L. Kamb, William Killean, James Newhall, Daniel Newman, Thomas A. Peterman, and Karen L. Willis

Acknowledgments

We thank Rae Lynn Burke of Chiron for provision of the strip immunoblot reagents and equipment and Denise Brown for performance of the laboratory assays

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Presented in part: National STD Prevention Conference, Milwaukee, 4–7 December 2000 (abstract A6)
Informed consent was obtained from all patients participating in the study. Human experimentation guidelines of the US Department of Health and Human Services and those of participating institutions were followed in the conduct of this research. The Project RESPECT protocol was reviewed and approved by the institutional review board at each participating site
Financial support: National Research Service Award grant 5 T32 PE10006 08; cooperative agreements with state and local health departments and the Centers for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention