HIV-1 Genital Shedding in Women Before and After Treatment for Cervical Dysplasia
Parent Project: UCSF-Gladstone Center for AIDS Research (CFAR)
The majority of the global HIV epidemic is occurring in sub-Saharan Africa, where the main route of transmission is heterosexual intercourse. An understanding of factors impacting transmission risk is necessary for effective prevention strategies, especially in countries such as Kenya, where the majority of infected individuals are in relationships with HIV-negative partners. One of the factors thought to be associated with sexual transmission is the presence and quantity of HIV-1 in the genital tract. The association between sexually transmitted infections (STIs) and increased risk of HIV transmission has been well studied and is thought to be partly attributable to increased levels of HIV-1 found in secretions of co-infected individuals. Human papillomavirus (HPV), the STI responsible for the vast majority of cervical cancers is found in up to 87% of HIV-infected women in Kenya. Women with HIV have a two- to ten-fold increase in risk for HPV infection and the subsequent development of cervical dysplasia and invasive cancer. Remarkably little is known about the potential impact of HPV-related dysplasia, and its treatment, on HIV-1 genital shedding. This pilot project explores the impact of the presence and treatment of HPV-related cervical dysplasia on HIV-1 in genital secretions. We will compare the levels of HIV-1 RNA found in the cervicovaginal secretions of women with no evidence of cervical dysplasia to levels in women with high-grade cervical dysplasia; we will also compare the levels of HIV-1 RNA prior to and up to 14 weeks after standard treatment for cervical dysplasia using loop electrosurgical excision procedure (LEEP). Study findings will have a potentially large epidemiologic impact on evaluation of HIV transmission risk and will help in the design and implementation of trials evaluating the safety and efficacy of various methods for treating cervical dysplasia among HIV-infected women. Results also have a potential immediate effect on counseling sero-discordant couples about periods of high infectivity following LEEP.