With an estimated 33 million persons living with HIV-1, 2.1 millions deaths from AIDS in 2007, and 2.5 million new HIV-1 infections per year worldwide, the global impact of HIV-1 and AIDS continues to be overwhelming, despite advances in treatment of chronic HIV-1 infection and improved access to treatment in developing countries Even in the United States, whose epidemic is dwarfed by that in developing countries, HIV-1 infection has had major health and social impacts: an estimated 1.3 million persons were living with HIV-1 infection and 56,000 people were newly infected in 2007[1,2]. Virologic and immunologic data germane to development of biomedical preventative strategies such as vaccines is critically important. 3.1 Viral Correlates of Sexual Transmission of HIV-1. The strongest viral correlate of sexual transmission has been plasma HiV-1 RNA levels[3,4]. HIV RNA levels in plasma and genital secretions correiate[5,6] and seminal plasma have been correlated with transmission probability[7,8]. More recent data suggest that distinct viral variants may be enriched in genital secretions compared with blood plasma although data are conflicting [9-12]. Many studies of sexual transmission over the years have shown that infections with HIV-1 subtype B typically (current estimates are ??70-80[13,14,15]) originate from single virus founders. However, data from heterosexual African women and men who had recently acquired HIV-1 subtypes A or D demonstrated that 20 of 32 women had multiple viral variants whereas all 10 of the men studied had a single variant^^. These data suggest that sex of the Infected individual or viral subtype might modify the characteristics of the transmitted virus. Other studies have suggested that other viral characteristics such as such as env glycoprotein N-llnked glycosylation or env lengths may impact transmissibility^^'^^, though again this may be subtype-specific[2021] (see Projects 1 and 3 for more detailed discussions).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI057005-09
Application #
8508169
Study Section
Special Emphasis Panel (ZCA1-GRB-T)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
9
Fiscal Year
2013
Total Cost
$255,374
Indirect Cost
$66,530
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hu, Xintao; Valentin, Antonio; Dayton, Frances et al. (2016) DNA Prime-Boost Vaccine Regimen To Increase Breadth, Magnitude, and Cytotoxicity of the Cellular Immune Responses to Subdominant Gag Epitopes of Simian Immunodeficiency Virus and HIV. J Immunol 197:3999-4013
Johnston, Christine; Harrington, Robert; Jain, Rupali et al. (2016) Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies. Biol Blood Marrow Transplant 22:149-56
Ma, Qing; Vaida, Florin; Wong, Jenna et al. (2016) Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients. J Neurovirol 22:170-8
Mothe, Beatriz; Hu, Xintao; Llano, Anuska et al. (2015) A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques. J Transl Med 13:60
Iyer, Shyamala; Casey, Eleanor; Bouzek, Heather et al. (2015) Comparison of Major and Minor Viral SNPs Identified through Single Template Sequencing and Pyrosequencing in Acute HIV-1 Infection. PLoS One 10:e0135903
Manocheewa, Siriphan; Mittler, John E; Samudrala, Ram et al. (2015) Composite Sequence-Structure Stability Models as Screening Tools for Identifying Vulnerable Targets for HIV Drug and Vaccine Development. Viruses 7:5718-35
Manocheewa, Siriphan; Lanxon-Cookson, Erinn C; Liu, Yi et al. (2015) Pairwise growth competition assay for determining the replication fitness of human immunodeficiency viruses. J Vis Exp :e52610
Stekler, Joanne D; McKernan, Jennifer; Milne, Ross et al. (2015) Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Antivir Ther 20:77-80
Sunshine, Justine E; Larsen, Brendan B; Maust, Brandon et al. (2015) Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape Processes in HIV-1 Infection. J Virol 89:10303-18
Maenza, Janine; Tapia, Kenneth; Holte, Sarah et al. (2015) How often does treatment of primary HIV lead to post-treatment control? Antivir Ther 20:855-63

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