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 #
1K23AI069990-01
Application #
7120952
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
2006-08-05
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$126,562
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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