Herpes simplex virus type 2 (HSV-2) infections is one of the driving forces behind the HIV epidemic In sub- Saharan Africa. This is especially true for adolescent/young women who acquire both infections rapidly after sexual debut. We hypothesize that genital inflammation among young women in sub-Saharan Africa is largely driven by HSV-2 acquisition. Our Sp.
Aim 1 will determine if HSV-2 acquisition among young African women results in persistent (>1 year) genital inflammation. The primary outcome will be the change in concentrations of the three pro-inflammatory factors MIP-ip, IL-1 a, and IL-8, measured by Luminex assays in cervicovaginal lavage (CVL) samples from adolescent women before and after initiation of sexual activity, and after HSV-2 seroconversion. We will test for other sexually transmitted infections, and for sexual activity by PSA, to determine their relative contribution to genital inflammation. A secondary clinical outcome will be the density of vulvar infiltration with HIV target cells, as measured by absolute densities of CCR5+ T cells, macrophages and dendritic cells (DCs), quantified by immunofluorescence staining vulvar biopsies obtained from women before and after HSV-2 acquisition. We will compare these biopsies to matched control women who are sexually active but remain HSV-2 seronegative. In year 1 we will conduct an exploratory microarray transcriptome study in an ex vivo vulvovaginal explant tissue model of HSV-2 infection. Our Sp Aim 2 will test whether the frequency of HSV-2 reactivation at set point correlates with the degree of inflammatory changes. We will establish a cohort of HSV-2/HIV negative adolescent women in Thika, Kenya. The women who acquire HSV-2 infection will be enrolled into a 60-day intensive study of HSV-2 shedding, during which they self-collect daily genital swabs for HSV-2 detection. The results on this study will define the role of HSV-2 in mucosal priming of young women for HIV acquisition upon exposure, provide insights into the mechanism, and lay foundation for future interventions for HSV-2 such as chemoprophylaxis, microbicides or vaccines.
In Africa, young women acquire genital herpes and then HIV in rapid succession. The mechanism by which having genital herpes increases the risk of HIV is not clear. We will follow a group of young Kenyan women from the time before they become sexually active and look at the effect on the genital tract of sexual activity and acquisition of genital herpes. This study is important for design of effective HSV-2 and HIV prevention.
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