My career objectives over the next five years are (1) to recruit and mentor young investigators interested in translational HIV research, (2) to further define the pathogenesis of drug-resistant HIV, and (3) to established a well-characterized cohort of HIV-seropositive individuals who in the absence of therapy are able to durably maintain undetectable plasma HIV RNA levels (the so-called """"""""elite"""""""" controllers). These goals will be pursued in the context of a multi-disciplinary research program aimed at translating basic research findings into the clinic while also collecting biologic specimens from well-characterized cohorts for focused laboratory-based research. Specifically, I will direct a study aimed at testing the hypothesis that drug-resistance mutations attenuate the pathogenicity of HIV. I will also direct two prospective pilot studies, one aimed at determining if antiretroviral therapy can be used intermittently to increase CD4+ T cell counts in patients with drug-resistant viremia and one aimed at preventing the establishment of drug-resistant virus in the latent reservoir. Finally, I will expand our model to include """"""""elite"""""""" controllers, and will direct a series of multi-disciplinary studies aimed at understanding the mechanisms of virus control in these individuals. I currently devote approximately 50% of total effort to clinical care and administrative/teaching responsibilities. With the support of a K24 award, I will decrease my clinical and teaching commitments, thus allowing me to focus on patient-oriented research and mentoring. Also, I will be able reduce my commitment as a co-investigator on grants that are not directly related to the aims outlined in this proposal. Public health implications: A significant and possibly growing proportion of HIV-infected patients harbor drug-resistant HIV. The studies outlined here will investigate novel approaches to prevent and manage HIV drug-resistance. Also, we believe that insights regarding the mechanisms operative in elite controllers will prove to be highly informative for future efforts aimed at preventing HIV infection and eradicating virus in those already infected. ? ? ?

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
Application #
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Fitzgibbon, Joseph E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
Zip Code
Scherzer, Rebecca; Shah, Sanjiv J; Secemsky, Eric et al. (2018) Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection. Circ Heart Fail 11:e004312
Kiniry, Brenna E; Li, Shengbin; Ganesh, Anupama et al. (2018) Detection of HIV-1-specific gastrointestinal tissue resident CD8+ T-cells in chronic infection. Mucosal Immunol 11:909-920
Rutishauser, Rachel Lena; Hartogensis, Wendy; Deguit, Christian Deo et al. (2017) Early and Delayed Antiretroviral Therapy Results in Comparable Reductions in CD8+ T Cell Exhaustion Marker Expression. AIDS Res Hum Retroviruses 33:658-667
Tawakol, Ahmed; Ishai, Amorina; Li, Danny et al. (2017) Association of Arterial and Lymph Node Inflammation With Distinct Inflammatory Pathways in Human Immunodeficiency Virus Infection. JAMA Cardiol 2:163-171
Paquin-Proulx, D; Ching, C; Vujkovic-Cvijin, I et al. (2017) Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection. Mucosal Immunol 10:69-78
Cockerham, Leslie R; Yukl, Steven A; Harvill, Kara et al. (2017) A Randomized Controlled Trial of Lisinopril to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Individuals. Pathog Immun 2:310-334
Ramirez, Christina M; Sinclair, Elizabeth; Epling, Lorrie et al. (2016) Immunologic profiles distinguish aviremic HIV-infected adults. AIDS 30:1553-62
Hsu, Denise C; Ma, Yi Fei; Hur, Sophia et al. (2016) Plasma IL-6 levels are independently associated with atherosclerosis and mortality in HIV-infected individuals on suppressive antiretroviral therapy. AIDS 30:2065-74
Ribeiro, Susan Pereira; Milush, Jeffrey M; Cunha-Neto, Edecio et al. (2016) p16INK4a Expression and Immunologic Aging in Chronic HIV Infection. PLoS One 11:e0166759
Chew, Glen M; Fujita, Tsuyoshi; Webb, Gabriela M et al. (2016) TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. PLoS Pathog 12:e1005349

Showing the most recent 10 out of 141 publications