Is Herpes Simplex Virus Type 1 (HSV-1) Now More Common than HSV-2 in First Episodes of Genital Herpes?

In this issue, Roberts et al. report that while HSV-2 was isolated more frequently from genital cultures at a Midwestern university from 1993 to 1997, HSV-1 became the predominant isolate type from 1997 to 2001. 1 Also in this issue, Samra et al. report that while HSV-2 was the predominate cause of genital herpes in Israel in the 1970s, HSV-1 was the principal cause of genital herpes among persons seeking care at a Tel Aviv medical center from 1993 to 2001. 2 Similarly, a Norwegian study found that 35% of initial first-episode genital herpes cases in 1987 to 1989 were attributable to HSV-1, compared to 66% in 1992 to 1995 and 51% in 1996 to 1998. 3 The changing epidemiology seems to be primarily affecting adolescents and young adults. 1-3 Roberts reports that HSV-1 was significantly more common in persons age 16 to 21 than in those ≥22 (64% versus 36%, P < 0.001). Among Norwegian patients, a significant increase in the proportion of HSV-1 isolates was noted in persons <21 with initial genital herpes between 1987 to 1989 (41%) and 1992 to 1995 (91%, P < 0.001) and 1996 to 1998 (70%, P < 0.001). There was not a similar significant change for persons 21 to 30, and the proportion of HSV-1 isolates for persons >30 years remained at or below 30%. Is HSV-1 now the predominant cause of first episode genital herpes for young persons? The short answer is that we do not know, but these studies certainly argue that HSV-1 is increasing and may be the major cause of new genital infections in certain populations. The two studies reported in this issue are not population-based and we have little demographic information on the participants. It would have been helpful to have information on the number of sexual partners, sexual practices, sexual orientation, socioeconomic status and race/ethnicity of the participants. However, population-based serostudies do not identify the site of infection, and studies that determine the HSV type isolated from first episodes of genital herpes will always be restricted to convenience samples that are not truly population-based. Lafferty et al. reported that HSV-1 was recovered from 164 (20%) of 821 culture-positive initial episodes, including 47% of males reporting sex with men (MSM) versus 21% of heterosexual females and 15% of heterosexual males among patients seen at the sexually transmitted diseases clinic in Seattle between 1993 and 1997. 4 Such detail on sexual history and other demographic information helps to highlight possible subpopulation effects, which is not available from other studies. 5-6 Ideally, future studies should seek such information in broad study populations or specific populations of interest. To insure adequate representation of adolescents and young adults, studies might be done in high school- and university-based health services and other settings where adolescents and young adults receive health care. Why is this increase occurring? One possibility may be that HSV-1 infections during childhood have declined so that more adolescents and young adults are HSV seronegative when they become sexually active. Most studies show that immunity resulting from prior HSV-1 infection (presumably nongenital) reduces the likelihood that an HSV-2 infection (presumably genital) will be symptomatic. 7 It is reasonable to assume that the same applies to genital HSV-1 infection; hence, for equal exposures, the adolescent with immunity to HSV-1 would be less likely to develop symptomatic genital HSV-1 infection compared to the HSV seronegative adolescent. The extent to which a decline in HSV-1 seroprevalence among adolescents and young adults has occurred over the past decade is unknown, but the anticipated analysis of the US population-based NHANES IV study may shed light on the US situation. A second explanation for the increase in incident HSV-1 genital herpes cases could be the emergence of more virulent strains of HSV-1. However, if this were the reason for the increase one might expect to see the increase across all age groups rather than principally among the young. A third explanation for the increase might be changes in sexual practices, particularly an increase in oral-genital sex. Lafferty et al. reported that white race and receptive oral sex in the 2 months before acquisition of genital herpes were significant positive predictors of HSV-1 infection. 4 The risk from receptive oral sex is obvious, whereas the risk associated with white race may result from both a higher incidence of oral sex and lower rates of childhood acquisition of non-genital HSV-1 infections compared to black and Hispanic populations in the US. 8,9 A study from the Northeastern US found that adolescents aged 15 to 17 years were significantly more likely to engage in oral sex than vaginal sex and report significantly greater numbers of oral sex partners as compared to sexual intercourse partners. 10 Studies suggest that 33%-59% of US high school adolescents, including 7%-24% of adolescent virgins, have engaged in oral sex 10 and higher rates of oral sex have been reported for adolescents in other countries. 11 Although there is no historical data on rates of oral sex, it has been suggested that an increasing emphasis on abstinence, HIV-related safe sex messages and a misconception that oral sex is safe and risk-free is leading to an increase in oral sex among adolescents and young adults. 12 What is clear is that the barrier protection, which might reduce the risk of acquiring a sexually transmitted infection during oral sex, is seldom used during oral sex. In contrast, in the US there has been an increase in condom use for vaginal intercourse by college students. 13 Because condoms have been shown to afford some protection against acquisition of HSV-2 infection, the increased use of condoms during sexual intercourse would be expected to decrease the incidence of genital HSV-2 infections. 14 By the same token, a decrease in protection afforded by prior oral HSV-1 infection, an increase in oral sex activities, and minimal use of barrier protection during oral sex may all combine to increase the incidence of genital HSV-1 infections among adolescents and young adults. What are the implications of the increase in the proportion of first-episodes caused by HSV-1? First, because genital HSV-1 infections recur less frequently, decrease in frequency more rapidly, and result in significantly less asymptomatic shedding, these infections should cause less long-term clinical morbidity and presumably should result in lower risk of transmission to neonates and to sexual partners. Second, population-based serosurveys that determine the prevalence of HSV-2 antibody undoubtedly underestimate the prevalence of genital HSV infections, particularly in populations that are shown to have high incident rates of genital HSV-1 infections. The changing epidemiology also has implications for strategies designed to control genital herpes. Safer sex messages need to be revised to include the risk of genital herpes resulting from oral-genital sex. Recent work demonstrating the usefulness of valaciclovir in reducing transmission of genital HSV-2 infection among discordant couples should be expanded to examine its value in reducing the oral to genital transmission of HSV-1. 15 Finally, vaccines intended to prevent genital herpes will need to be effective against both HSV-1 and HSV-2 infections. Fortunately, the recombinant glycoprotein D vaccine that was recently shown to afford women some protection against genital herpes caused by HSV-2 has also been shown in animal studies to protect equally well against genital HSV-1 infection. 16,17 Vaccines intended to prevent genital HSV infections will need to be administered to preadolescents in order to provide broadest coverage, including protection against genital HSV-1 in the virginal adolescent.