Reply to Flom et al.

    Division of Sexually Transmitted Disease Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

    The study by Flom et al. [1] allows a comparison of the correlates of herpes simplex virus type 2 (HSV-2) infection in a representative community-based sample of low-income youth in Brooklyn, New York, with the correlates of infection in our larger sample of patients from 5 sexually transmitted disease (STD) clinics [2]. Despite the fact that our STD clinic sample was self-selected for riskier behavior and represented only 43% of those eligible to participate, Flom et al. replicated most of our observations, supporting the generalizability of these findings. Similar effect sizes were observed for such risk factors as female sex, black race, less education, prior diagnosis of STD, and greater number of lifetime sex partners, which suggests that these factors are important in multiple populations. Indeed, most of these risk factors were identified in a large population-based, nationally representative evaluation of HSV-2 seroprevalence [3].

    Unlike our study, the study by Flom et al. showed no association between HSV-1 infection and the seroprevalence of HSV-2, and they offered several possible explanations for this difference. Although all of their explanations are plausible, the association between HSV-1 and HSV-2 infection is best evaluated in prospective studies, given that the timing and rates of each infection with respect to the other are unknown in cross-sectional studies. In fact, when we monitored our STD clinic study population prospectively to determine risk factors for new HSV-2 infections, prior HSV-1 infection did not protect against the subsequent acquisition of HSV-2 [4]. One possible explanation for the difference between the inverse association of HSV-1 and HSV-2 infection observed in our seroprevalence study and the lack of such an association in our seroincidence study might be a protective effect of HSV-2 infection on subsequent HSV-1 acquisition, which has been suggested by previous studies [5, 6]. Given the high prevalence of HSV-2 infection even among the youngest age groups in our study, HSV-2 infection could precede HSV-1 acquisition in a portion of this high-risk population.

    Another difference between the study by Flom et al. and our seroprevalence study was the strength of association between HSV-2 seroprevalence and age at first sexual intercourse. Age at first sexual intercourse was much more strongly associated with HSV-2 infection in the community sample. In our study, age at first sexual intercourse was mildly associated with HSV-2 infection in bivariate analysis; yet, after controlling for other characteristics, such as age and number of lifetime sex partners, we found no association between age at first sexual intercourse and HSV-2 infection. Perhaps among the higher-risk STD clinic population, who had >3 times the median number of lifetime sex partners than the population in the community sample, age at first sexual intercourse was not as discriminating in separating out risk groups for HSV-2 infection. However, a similar lack of association between age at first sexual intercourse and HSV-2 infection was found in the general US population [3].

    Finally, in their study, Flom et al. were able to explore, to a greater degree than was possible in our study, 2 of the most consistent risk factors for HSV-2 infectionfemale sex and black race. Fleming et al. [3] had postulated that the high prevalence 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. We considered this to be unlikely as a primary explanation for the higher prevalence of HSV-2 infection in women, because we found that HSV-2 seroprevalence was generally higher among younger women than among considerably older men. However, we had no data on the age of the sex partners of the women in our study. Flom et al. found that having an older partner was a risk factor for HSV-2 infection, yet this factor did little to explain the overall difference in HSV-2 prevalence between men and women, which is consistent with our observations. However, it is important to keep in mind that HSV-2 seroprevalence reflects lifetime exposure to a risk factor. Therefore, the effect of a current sex partner or of a single partner within the past year would not necessarily be expected to predict prevalent HSV-2 infection, unless that partner choice corresponds to a lifetime pattern. The distinction between lifetime and recent exposure is also important with respect to race. Thus, although Flom et al. found no difference in HSV-2 seroprevalence between nonblacks with and without a black sex partner during the preceding 12 months, this finding does not refute our assertion that the preferential selection of partners within the same racial/ethnic group may contribute to the higher HSV-2 seroprevalence in blacks.

    References

    1.  Flom PL, Zenilman JM, Sandoval M, Kottiri BJ, Friedman SR. Seroprevalence and correlates of herpes simplex virus type 2 among young adults in a low-income minority neighborhood. J Infect Dis 2005; 191:81820 [in this issue]. First citation in article

    2.  Gottlieb SL, Douglas JM Jr, Schmid DS, et al., for the Project RESPECT Study Group. Seroprevalence and correlates of herpes simplex virus type 2 infection in five sexually transmitteddisease clinics. J Infect Dis 2002; 186:13819. First citation in article

    3.  Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997; 337:110511. First citation in article

    4.  Gottlieb SL, Douglas JM Jr, Foster M, et al. Incidence of herpes simplex virus type 2 infection in five sexually transmitted disease clinics and the effect of HIV/STD risk-reduction counseling. J Infect Dis 2004; 190:105967. First citation in article

    5.  Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:50915. First citation in article

    6.  Nahmias AJ, Lee FK, Beckman-Nahmias S. Sero-epidemiological and -sociological patterns of herpes simplex virus infection in the world. Scand J Infect Dis 1990; 69(Suppl):1936. First citation in article