This K23 patient oriented career development award application is for Brenna Anderson, M.D., M.Sc. Dr. Anderson is a Maternal Fetal Medicine specialist with additional training in clinical research and reprodcutive infectious diseases. Dr. Anderson's training and research plans are designed to develop an independent research career on HIV in women with a focus on risk of HIV acquisition in pregnancy. It will address the trans-NIH plan for HIV-related research for Women and Girls objective: To elucidate biologic determinants of HIV transmission and define the mechanisms by which viral, host, and immune factors may influence the process of HIV transmission, acquisition, and resistance to infection among women and girls across the life cycle. The training plan involves four focus areas:! gaining expertise in HIV care as it applies to research protocols, 2. training in clinical HIV research topics that are unique to women and minorities, 3. acquisition of knowledge in reproductive immunology relevant to HIV and translational research, and 4. formal training in professional development. Dr. Anderson will acquire the necessary skills develop an independent research program. The research plan will determine the risk of HIV infectivity among uninfected pregnant women using a TZM-bl in vitro infectivity assay. A prospective cohort study of 37 pregnant and 37 non-pregnant women will be enrolled and followed with serial cervicovaginal lavage collections. The study goal is to show that protection against HIV infection during pregnancy is reduced due to decreased endogenous antimicrobial components in the genital immune tract during pregnancy.The hypothesis to be tested is that the cervicovaginal lavage (CVL) of pregnant women will inhibit HIV infectivity to a lesser extent than that of non-pregnant women. The primary study aims will be 1. To compare anti-HIV properties of CVL from pregnant and non-pregnant women in a TZM-bl assay and 2. To identify and quantify the endogenous innate immune antivirals in the CVL responsible for inhibition of the infectivity assays. The secondary aims will be 3. To examine the impact that disruption of normal vaginal flora in the form of bacterial vaginosis has on HIV infectivity, and 4: To evaluate the impact of host race/ethnicity on the anti-HIV properties of CVL.

Public Health Relevance

Pregnant women may be at increased risk for HIV acquisition and the implications of this include a possible increase in mother to child HIV transmission. Key factors in heterosexual transmission in pregnancy must be elucidated to develop preventive measures that are safe and effective in pregnant women. Endogenous components of the immune system could be used in development of microbicides during pregnancy.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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AIDS Clinical Studies and Epidemiology Study Section (ACE)
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Mofenson, Lynne M
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Women and Infants Hospital-Rhode Island
United States
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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
Dutt, Riana; Raker, Christina; Anderson, Brenna L (2015) Ethnic variations in cervical cytokine concentrations and vaginal flora during pregnancy. Am J Reprod Immunol 73:141-50
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
McDonnold, Mollie A; Friedman, Alexander M; Raker, Christina A et al. (2012) First-trimester pyelonephritis is associated with later initiation of prenatal care: a retrospective cohort analysis. Am J Perinatol 29:141-6
Johnson, Julie; Anderson, Brenna; Pass, Robert F (2012) Prevention of maternal and congenital cytomegalovirus infection. Clin Obstet Gynecol 55:521-30
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
Anderson, Brenna L; Ghosh, Mimi; Raker, Christina et al. (2012) In vitro anti-HIV-1 activity in cervicovaginal secretions from pregnant and nonpregnant women. Am J Obstet Gynecol 207:65.e1-10
Anderson, Brenna L; Cu-Uvin, Susan (2011) Clinical parameters essential to methodology and interpretation of mucosal responses. Am J Reprod Immunol 65:352-60
Anderson, Brenna L; Cu-Uvin, Susan; Raker, Christina A et al. (2011) Subtle perturbations of genital microflora alter mucosal immunity among low-risk pregnant women. Acta Obstet Gynecol Scand 90:510-5
Mendez-Figueroa, Hector; Raker, Christina; Anderson, Brenna L (2011) Neonatal characteristics and outcomes of pregnancies complicated by influenza infection during the 2009 pandemic. Am J Obstet Gynecol 204:S58-63

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