Antiviral Therapy and HIV in the Genital tract of Women. About 40 million adults are estimated to be living with HIV/AIDS. 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. Understanding the dynamics of HIV-1 in the genital tract is of great importance in strategies to control sexual and perinatal transmission of HIV.
The specific aims of this study are: 1) To understand the relative dynamics of viral failure and viral replication in the genital tract, 2) To assess drug exposure and patterns of drug resistance in the female genital tract and 3) To evaluate cellular reservoirs in the female genital tract. To address issues of viral failure, development of resistance, and drug levels, we will enroll 50 HIV (+) women who are failing their current antiviral regimen. We will assess paired plasma and genital tract secretions at multiple time points for: viral load, genotyping, and peak and trough drug levels before and after changing therapy. To evaluate latent reservoirs in the genital tract, we will enroll 50 HIV (+) women who are fully suppressed on antiviral therapy and propose to collect endocervical cells by a swab/cytobrush technique in an attempt to recover replication competent virus. We also propose to enroll women who have undergone total hysterectomy to assess HIV dynamics in the vagina.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI040350-06A2
Application #
6656086
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (06))
Program Officer
Livnat, Daniella
Project Start
1997-04-15
Project End
2008-04-30
Budget Start
2003-05-16
Budget End
2004-04-30
Support Year
6
Fiscal Year
2003
Total Cost
$571,660
Indirect Cost
Name
Miriam Hospital
Department
Type
DUNS #
063902704
City
Providence
State
RI
Country
United States
Zip Code
02906
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Ghosh, Mimi; Shen, Zheng; Fahey, John V et al. (2010) Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract. Immunology 129:207-19
Cu-Uvin, Susan; DeLong, Allison K; Venkatesh, Kartik K et al. (2010) Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS 24:2489-97
Ghosh, Mimi; Fahey, John V; Shen, Zheng et al. (2010) Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies. PLoS One 5:e11366
Mitchell, Caroline; Moreira, Carla; Fredricks, David et al. (2009) Detection of fastidious vaginal bacteria in women with HIV infection and bacterial vaginosis. Infect Dis Obstet Gynecol 2009:236919
Moreira, Carla; Venkatesh, Kartik K; DeLong, Allison et al. (2009) Effect of treatment of asymptomatic bacterial vaginosis on HIV-1 shedding in the genital tract among women on antiretroviral therapy: a pilot study. Clin Infect Dis 49:991-2
Anderson, Brenna L; Wang, Chia-Ching; Delong, Allison K et al. (2008) Genital tract leukocytes and shedding of genital HIV type 1 RNA. Clin Infect Dis 47:1216-21

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