The overarching goals of this proposal are to further our understanding of the effect of potent antiretroviral therapy (ART) on Human Immunodeficiency Virus Type 2 (HIV-2) infection. HIV-2 is generally less pathogenic than HIV-1. Compared to HIV-1, HIV-2 infection is characterized by a much longer asymptomatic stage, lower plasma viral loads, slower decline in CD4+ T cell count, decreased mortality rate due to AIDS, lower rates of mother to child transmission, and lower rates of sexual transmission. Nonetheless, a significant proportion of HIV-2 infected individuals eventually progress to AIDS. Antiretrov'iral therapy is becoming increasingly available in resource-limited settings. In Senegal where both HIV-1 and HIV-2 are found, a national program of providing antiretroviral treatment (ART) for those with AIDS, CD4+ T cell counts less than 200/mm3, or CD4+ T cell counts less than 350/mm3 and clinical symptoms has been established. However, the effects of ART on outcome, immunologic response, viral load, dynamics and evolution, HIV-2 drug resistance and fitness in HIV-2 infected individuals are largely unknown. Our longstanding longitudinal cohort of HIV-2 infected subjects from Dakar, Senegal provides a unique opportunity to study the role ART plays in suppressing HIV-2 infection.
The Specific Aims of this proposal are:
AIM 1 : To determine the clinical, virologic and immunologic outcomes associated with antiretroviral therapy (ART) in a longitudinal prospective HIV-2 infected Senegalese cohort.
AIM 2 : To assess role of drug resistance in viruses that emerge in HIV-2 infected subjects with virologic failure and to determine if there are qualitative and quantitative differences the drug resistant viruses that emerge between HIV-2 and HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI060466-03
Application #
7189880
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Huebner, Robin E
Project Start
2005-06-07
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
3
Fiscal Year
2007
Total Cost
$628,409
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Smith, Robert A; Wu, Vincent H; Zavala, Christopher G et al. (2018) In Vitro Antiviral Activity of Cabotegravir against HIV-2. Antimicrob Agents Chemother 62:
Chang, Ming; Wong, Audrey J S; Raugi, Dana N et al. (2017) Clinical validation of a novel diagnostic HIV-2 total nucleic acid qualitative assay using the Abbott m2000 platform: Implications for complementary HIV-2 nucleic acid testing for the CDC 4th generation HIV diagnostic testing algorithm. J Clin Virol 86:56-61
Wu, Vincent H; Smith, Robert A; Masoum, Sara et al. (2017) MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture. Antimicrob Agents Chemother 61:
Whitham, Hilary K; Hawes, Stephen E; Chu, Haitao et al. (2017) A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-Positive and HIV-Negative Women in Senegal, Africa. Cancer Epidemiol Biomarkers Prev 26:886-894
Chang, Ming; Steinmetzer, Katrin; Raugi, Dana N et al. (2017) Detection and differentiation of HIV-2 using the point-of-care Alere q HIV-1/2 Detect nucleic acid test. J Clin Virol 97:22-25
Raugi, Dana N; Smith, Robert A; Gottlieb, Geoffrey S et al. (2016) Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors. J Virol 90:1062-9
Smith, Robert A; Raugi, Dana N; Wu, Vincent H et al. (2015) The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1. Antimicrob Agents Chemother 59:7437-46
Smith, Robert A; Raugi, Dana N; Pan, Charlotte et al. (2015) In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Retrovirology 12:10
Gottlieb, Geoffrey S (2013) Changing HIV epidemics: what HIV-2 can teach us about ending HIV-1. AIDS 27:135-7
Hanisch, R A; Sow, P S; Toure, M et al. (2013) Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal, West Africa. J Clin Virol 58:696-702

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