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Background:  Increasing evidence indicates that prior sexually transmitted herpes simplex virus type 2 (HSV-2) infection facilitates HIV-1 transmission, so discovery of factors that promote or prevent HSV-2 infection may help alter the HIV/AIDS epidemic. We examined the epidemiological and immunogenetic correlates of HSV-2 infection in a cohort of sexually active adolescents.
Methods:  Sero-positivity for HIV-1, HSV-2, and HSV-1 was determined by screening 530 adolescents enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) study. Major human leukocyte antigen (HLA) and cytokine gene variants frequently targeted in various studies were defined by polymerase chain reaction (PCR)-based techniques. Epidemiological and immunogenetic factors related to HSV-2 infection were analyzed by univariate and multivariable logistic regression methods.
Results:  We identified 171 prevalent and 44 incident cases of HSV-2 infection during 853 person-visits. Gender, time since first sexual activity, and prevalent HIV-1 infection were independently associated with HSV-2 infection (p < 0.01 for all). Human leukocyte antigen (HLA) alleles A*01, A*68, DRB1*07, and the DRB1*04-DQB1*03 haplotype were weakly associated with HSV-2 infection in univariate analyses (P = 0.01 to 0.05). Multivariable analyses revealed that the (-330)G to 166G haplotype in the interleukin-2 (IL-2) locus and the (-1098)T to (-590)C-(-33)C haplotype in the IL-4 promoter were negatively associated with HSV-2 infection (adjusted odds ratio = 0.49 to 0.59; p =  0.017 and 0.015, respectively). These genetic relationships were also observed in separate analyses of incident HSV-2 infection and in analyses accounting for concomitant HIV-1 or HSV-1 infection.
Conclusions:  In addition to epidemiological factors predisposing adolescents to HSV-2 infection, our findings implicate host genetic polymorphisms, especially those in cytokine gene systems, as informative markers. The effects of these polymorphisms appear to be independent of co-infection with HSV-1 or HIV-1.

Keywords: HSV-2; genetics; adolescent