I have had the opportunity to develop a clinical research career in HIV in women and more specifically on HIV-1 shedding in the female genital tract. The purpose of this application for a Mid-career Investigator Award in Patient-Oriented Research (K24) is to provide the framework within which I can mentor junior clinical investigators in patient-oriented research focused on critical issues related to HIV in women. This proposal builds on the existing resources at our institution that has a robust track record of training junior faculty to become independent investigators. Our institution is committed to research training that can prepare the next generation of physicians to bridge the gaps in our knowledge in HIV infection. The Division of Infectious Diseases at the Miriam Hospital, Brown Medical School, includes NIH funded Adult AIDS Clinical Trials Unit, the Brown/Tufts/Lifespan Center of AIDS Research, the AIDS International Training and Research Program, the Center for Drug Addiction and AIDS Research, and NIH funded training grants. About 37-40 million adults are estimated to be living with HIV/AIDS and half of these are women. The predominant mode of HIV transmission worldwide is through heterosexual contact. Although many factors are associated with sexual transmission of HIV-1 (both behavioral and biologic), HIV-1 viral load has been identified as the chief predictor of the risk of sexual transmission. Levels of HIV-1 viral load have been associated with mother-to-infant transmission of HIV. Several studies have also shown a good correlation between blood plasma viral load and male and female genital tract viral load. The use of antiretroviral medications can reduce blood plasma HIV-1 RNA levels as well as genital tract HIV-1 RNA. Studies have also shown a reduction in perinatal transmission with effective antiretroviral therapy. Transmission of drug resistant HIV-1 has been reported in the US and Europe ranging from 2% to 27% among newly infected patients. There have been reports of resistant genotypic variants in both male and female genital tract that is different from those of blood. These findings underscore the risk of spreading resistant HIV-1 variants sexually as well as perinatally. With my research, I hope to be able to help contribute to the work on HIV treatment and prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AI066884-05
Application #
7638668
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Livnat, Daniella
Project Start
2005-08-15
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2011-06-30
Support Year
5
Fiscal Year
2009
Total Cost
$153,284
Indirect Cost
Name
Miriam Hospital
Department
Type
DUNS #
063902704
City
Providence
State
RI
Country
United States
Zip Code
02906
Hughes, Brenna L; Dutt, Riana; Raker, Christina et al. (2016) The impact of pregnancy on anti-HIV activity of cervicovaginal secretions. Am J Obstet Gynecol 215:748.e1-748.e12
Anderson, Brenna L; Mendez-Figueroa, Hector; Dahlke, Joshua D et al. (2013) Pregnancy-induced changes in immune protection of the genital tract: defining normal. Am J Obstet Gynecol 208:321.e1-9
Venkatesh, Kartik K; DeLong, Allison K; Kantor, Rami et al. (2013) Persistent genital tract HIV-1 RNA shedding after change in treatment regimens in antiretroviral-experienced women with detectable plasma viral load. J Womens Health (Larchmt) 22:330-8
Firth, Jacqueline; Wang, Chia-Ching; Gillani, Fizza et al. (2012) The changing face of HIV in pregnancy in Rhode Island 2004-2009. Infect Dis Obstet Gynecol 2012:895047
Kang, M; Cu-Uvin, S (2012) Association of HIV viral load and CD4 cell count with human papillomavirus detection and clearance in HIV-infected women initiating highly active antiretroviral therapy. HIV Med 13:372-8
Lahey, Timothy; Ghosh, Mimi; Fahey, John V et al. (2012) Selective impact of HIV disease progression on the innate immune system in the human female reproductive tract. PLoS One 7:e38100
Nijhawan, A E; Delong, A K; Chapman, S et al. (2012) Effect of HSV-2 suppressive therapy on genital tract HIV-1 RNA shedding among women on HAART: a pilot randomized controlled trial. Infect Dis Obstet Gynecol 2012:868526
Mabeya, Hillary; Khozaim, Kareem; Liu, Tao et al. (2012) Comparison of conventional cervical cytology versus visual inspection with acetic acid among human immunodeficiency virus-infected women in Western Kenya. J Low Genit Tract Dis 16:92-7
Mukura, Lucy R; Ghosh, Mimi; Fahey, John V et al. (2012) Genital tract viral load in HIV Type 1-positive women correlates with specific cytokine levels in cervical-vaginal secretions but is not a determinant of infectious virus or anti-HIV activity. AIDS Res Hum Retroviruses 28:1533-9
Anderson, Brenna L; Firnhaber, Cynthia; Liu, Tao et al. (2012) Effect of trichomoniasis therapy on genital HIV viral burden among African women. Sex Transm Dis 39:638-42

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