Candidate: Susan Graham, MD, MPH, is a Senior Fellow in Infectious Diseases at the University of Washington (UW) with training in internal medicine and public health and over 4 years of experience in international research. During her fellowship, she has studied HIV-1 genital tract shedding among antiretroviral-treated women in Kenya. Her immediate goals are to complete several prospective cohort studies of the impact of antiretroviral therapy on genital tract shedding, and to complete a doctoral degree in epidemiology. Her long-term objective is to become an independent investigator, leading a research team on the clinical epidemiology, prevention, and treatment of HIV infection in resource-limited settings. Environment: The UW, with its Center for AIDS Research, International AIDS Research and Training Program, and outstanding graduate-level training programs, is ideal for career development in international HIV/AIDS research. Dr. Graham will be supervised by her current mentors, Drs. King Holmes and Scott McClelland, and will collaborate with Dr. Julie Overbaugh's HIV-1 virology laboratory. The Mombasa field site provides administrative infrastructure, strong laboratory support, and a record of having successfully conducted many large epidemiologic studies. A cohort of HIV-1 seropositive patients established by Dr. Graham in a new clinic north of Mombasa provides ample opportunities for development of future projects. Research: In resource-limited settings, patients who fail first-line antiretroviral therapy have limited options and may transmit drug-resistant virus. The proposed prospective cohort study will evaluate the effectiveness of second-line therapy at suppressing HIV-1 replication in both plasma and genital tract secretions. We will evaluate resistance at failure of first-line therapy, subsequent viral suppression by second-line therapy, and correlates of continued HIV-1 genital shedding. Unique aspects of this study include the focus on women at high risk for transmission, enrollment from two ongoing cohorts with data on first-line therapy history, and our group's extensive research experience in studies of HIV-1 genital shedding. Relevance: We propose to study HIV-1 in blood and genital secretions of high-risk women starting second-line antiretroviral therapy. As HIV therapy is scaled up, research on drug resistance and the success of second-line treatment is crucial, and Dr. Graham is poised to make an important contribution in this area..

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI069990-05
Application #
7874613
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Huebner, Robin E
Project Start
2006-08-05
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
5
Fiscal Year
2010
Total Cost
$126,671
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
Korhonen, Christine J; Srinivasan, Sujatha; Huang, Dandi et al. (2017) Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men. J Acquir Immune Defic Syndr 74:250-257
Graham, Susan M; Chohan, Vrasha; Ronen, Keshet et al. (2016) Genital Shedding of Resistant Human Immunodeficiency Virus-1 Among Women Diagnosed With Treatment Failure by Clinical and Immunologic Monitoring. Open Forum Infect Dis 3:ofw019
Graham, Susan M; Raboud, Janet; Jaoko, Walter et al. (2014) Changes in sexual risk behavior in the Mombasa cohort: 1993-2007. PLoS One 9:e113543
Graham, Susan M; Raboud, Janet; McClelland, R Scott et al. (2013) Loss to follow-up as a competing risk in an observational study of HIV-1 incidence. PLoS One 8:e59480
Graham, Susan M; Holte, Sarah E; Dragavon, Joan A et al. (2012) HIV-1 RNA may decline more slowly in semen than in blood following initiation of efavirenz-based antiretroviral therapy. PLoS One 7:e43086
Graham, Susan M; Jalalian-Lechak, Zahra; Shafi, Juma et al. (2012) Antiretroviral treatment interruptions predict female genital shedding of genotypically resistant HIV-1 RNA. J Acquir Immune Defic Syndr 60:511-8
Graham, Susan M; Masese, Linnet; Gitau, Ruth et al. (2011) Genital ulceration does not increase HIV-1 shedding in cervical or vaginal secretions of women taking antiretroviral therapy. Sex Transm Infect 87:114-7
Graham, Susan M; Krieger, John N; Githua, Peter L M et al. (2011) Post-prostatic massage fluid/urine as an alternative to semen for studying male genitourinary HIV-1 shedding. Sex Transm Infect 87:232-7
Graham, Susan M; Masese, Linnet; Gitau, Ruth et al. (2010) Antiretroviral adherence and development of drug resistance are the strongest predictors of genital HIV-1 shedding among women initiating treatment. J Infect Dis 202:1538-42
Graham, Susan M; Shah, Prakesh S; Aesch, Zoe Costa-von et al. (2009) A systematic review of the quality of trials evaluating biomedical HIV prevention interventions shows that many lack power. HIV Clin Trials 10:413-31

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