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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HD062340-04
Application #
8306898
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Mofenson, Lynne M
Project Start
2009-08-10
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$132,921
Indirect Cost
$9,846
Name
Women and Infants Hospital-Rhode Island
Department
Type
DUNS #
069851913
City
Providence
State
RI
Country
United States
Zip Code
02905
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; 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
Anderson, Brenna; Zhao, Yuan; Andrews, William W et al. (2011) Effect of antibiotic exposure on Nugent score among pregnant women with and without bacterial vaginosis. Obstet Gynecol 117:844-9
Anderson, Brenna L; Rouse, Dwight J; Fitzsimmons, Christine (2011) Clinical characteristics of pregnant women with influenza-like illness during the 2009 H1N1 pandemic and use of a standardized management algorithm. Am J Obstet Gynecol 204:S31-7