Genital ulcer disease (GUD) is a significant risk factor for the bidirectional transmission of the human immunodeficiency virus type-1 (HIV-1). A number of biologic and molecular mechanisms have been proposed which likely account for this increased risk, including disruption of the protective epithelial/mucosal barrier, recruitment of activated inflammatory cells, and increased replication of HIV-1 at the genital ulcer. In vitro studies have provided evidence that at least one HIV-1 coreceptor (CCR5) is upregulated after stimulation of human monocytes with T. pallidum. There is, however, a paucity of in vivo data confirming many of these molecular findings. Given that HIV infection remains an alarming global public health problem, and that co-infection with GUD is common, studies to further elucidate this interrelationship at the cellular and molecular levels is vital to our understanding of and possible prevention of HIV transmission. The potential role pregnancy and/or elevated progesterone levels play in altering HIV transmission has not been investigated, yet may be a major confounder. To this end, the Specific Aims of this proposal are: 1) To characterize the inflammatory milieu in GUD and determine the effect on HIV-1 coreceptor expression in HIV-1 uninfected women with GUD; 2) To determine the effect of GUD on HIV-1 expression in HIV- 1 infected women; and 3) To determine the influence of pregnancy on the inflammatory milieu and HIV-1 coreceptor expression in the setting of GUD. The pursuit of these aims will further elucidate the cellular and molecular bases of the interrelationship between GUD and HIV-1 transmission, particularly in women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD041358-03
Application #
6744733
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Watts, Heather
Project Start
2002-05-01
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
3
Fiscal Year
2004
Total Cost
$124,200
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Sheffield, Jeanne S; Wendel Jr, George D; McIntire, Donald D et al. (2009) The effect of progesterone levels and pregnancy on HIV-1 coreceptor expression. Reprod Sci 16:20-31
Sheffield, Jeanne S; Wendel Jr, George D; McIntire, Donald D et al. (2007) Effect of genital ulcer disease on HIV-1 coreceptor expression in the female genital tract. J Infect Dis 196:1509-16