Studies of our adolescent population in Washington D.C. demonstrate that HIV infection is present in this population and that the seroprevalence rate is higher than in other nonselect groups. Many HIV+ adolescent females are given oral contraceptive pills to prevent pregnancy. This hormonal potentiation increases cervical ectopy that results in the presentation of the cervical squamocolumnar junction on the visible face of the ectocervix. This columnar epithelium is composed of a single cell layer and is more accessible to HIV-infected circulating cells than the stratified squamous epithelium of the vaginal wall and most of the ectocervix. This could impact transmission of HIV in adolescents by increasing either the shed of HIV or increasing susceptibility to infection. The long range goal of this proposal is to define the factors that influence transmission in adolescents in order to block or interfere with transmission. We propose to test the hypothesis that the genetic diversity of gp12O of the HIV quasispecies found in the cervical mucosa is different than the diversity in peripheral blood mononuclear cells (PBXC) and furthermore that oral contraceptive pills affect the genetic diversity of the HIV quasispecies in the cervical mucosa. We have chosen to concentrate on gpl2O because viral phenotypic and genetic variations in gpl20 influence disease progression in AIDS patients and potentiate perinatal transmission. To extend these results, we will use a recently developed in vitro model that is similar to the normal cervical epithelium to define the genetic diversity of HIV that replicates in a CD4 negative, cervix-derived cell line (ME18O). These studies are designed to provide a better understanding of the basic mechanisms of sexual transmission of HIV and factors that influence it. Ultimately, this understanding will lead to new strategies to prevent transmission.
| Holland, C A; Ellenberg, J H; Wilson, C M et al. (2000) Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network. AIDS Res Hum Retroviruses 16:959-63 |
