Genital herpes in high risk HIV-1 infected and HIV-1 uninfected women in US: Quantitative and qualitative evaluation of HSV infection and its interaction with HIV-1

Background. Recent evidence suggests existence of a synergistic interaction between Human Immunodeficiency Virus 1 (HIV-1) and Herpes Simplex Virus Type 2 (HSV-2). Despite this evidence epidemiological data remain conflicting. This dissertation research was conducted to qualitatively and quantitatively explore genital HSV course and its interactions with HIV-1 within the setting of the Women's Interagency HIV-1 longitudinal study (WIHS).;Methods. This dissertation consists of three studies. The first study developed and evaluated the utility of quantitative Real Time TaqMan Polymerase Chain Reaction (PCR) for detection and quantification of HSV-2 shedding in cervicovaginal lavage (CVL) specimens collected from participants of WIHS. The second study explored correlates of cervicovaginal HSV-2 shedding in the context of HSV-2 natural history among 369 HIV-1 infected and 63 uninfected HSV seropositive women. The third study explored the role of HSV-2 clinical reactivation on HIV-1 replication among highly active antiretroviral therapy (HAART) naive HIV-1 infected HSV-2 seropositive women of WIHS.;Results. Study 1: The assay demonstrated to have potential utility for identifying individuals with wide linear range of HSV-2 DNA shedding in genital secretions. Overall, 7% of the 509 tested samples were found positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). Study 2: Detection and quantity of HSV-2 DNA shedding were higher in HIV-1 infected than HIV-1 uninfected women. The quantity of HSV-2 DNA load was significantly correlated with the number of subsequent lesion-episodes observed during the study. HSV-2 shedding decreased with age reflecting decrease in HSV-2 recurrences observed during the study follow up. Study 3: A positive association was found between HSV-2 clinical reactivation and plasma HIV-1 RNA levels. Severity of HSV-2 clinical expression was correlated with the severity of HIV-1 disease.;Conclusion. This research identified new and supports previously described correlates of genital HSV-2 shedding. It provided important insights on the natural course of HSV-2 among HIV-1 infected women and demonstrated that multiple herpes recurrences promote HIV-1 replication and thus may contribute to poor prognosis of HIV-1. Results of this research have implications for prevention and management of HSV-2 infections in HIV-1 infected and high risk uninfected women.