VIROLOGIC AND HOST FACTORS CONTRIBUTING TO HIV CONTROL IN ELITE CONTROLLERS
Hiroyu Hatano
University Of California San Francisco, 3333 California St., Ste 315, San Francisco, Ca 94143-0962
Grant 5K23AI075985-03 from National Institute Of Allergy And Infectious Diseases
Abstract: This is an application for a K23 award for Dr. Hiroyu Hatano, a fellow in adult infectious diseases at the University of California, San Francisco who is establishing herself as a young investigator in patient-oriented translational research of HIV-infected elite controllers. Elite controllers are HIV-antibody individuals who have maintained "undetectable" plasma HIV-1 RNA levels in the absence of antiretroviral therapy. This K23 award will provide Dr. Hatano with the support necessary to accomplish the following goals (1) to recover, quantify, and characterize HIV in elite controllers; (2) to examine the interactions between host and virologic factors that contribute to effective virologic control in elite controllers; and (4) to develop an independent, clinic-based translational research career. To achieve these goals, Dr. Hatano has assembled a mentoring team comprised of her primary mentor, Dr. Steven G. Deeks, an expert in translational HIV research with a focus on HIV pathogenesis, and three co-mentors Dr. Joseph K. Wong, a clinical virologist and expert in HIV latency; Dr. Joseph (Mike) McCune, an immunologist with expertise in the immunology of HIV infection; and Dr. Jeffrey N. Martin, an expert in infectious diseases and epidemiology. Although highly active antiretroviral therapy (HAART) has been effective in decreasing the morbidity and mortality associated with HIV infection for patients with access to medical care, the challenges of long-term efficacy, toxicity, cost, and life-long adherence remain. Thus, models of eradication need to be examined in order to elucidate potential host and viral factors that may make eradication possible. One such model is the elite controller cohort. Although rare, elite controllers provide a unique opportunity to study a naturally occurring model of sustained control of HIV. Dr. Hatano will identify both virologic factors (Aim 1) and host factors (and their interactions) (Aim 2) that contribute to the effective control of HIV in elite controllers, and she will examine whether a proportion of them have "cleared" their HIV infection (Aim 3). This research will provide Dr. Hatano with the skills and preliminary data to successfully compete for R34 (Year 4) and U01 (Year 5) NIH grant support that will focus specifically on HIV latency and control of HIV in elite controllers and whether treatment with HAART or others methods aimed at depletion of HIV can eradicate HIV in elite controllers. Insight into how elite controllers maintain their distinctive version of HIV latency and durable viral control may affect HIV treatment strategies, bolster therapeutic vaccine design efforts, and contribute to the possible eradication of HIV
Keywords: 21+ years old; AIDS Antibodies; AIDS Virus; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Acute; Adherence; Adherence (attribute); Adult; Adverse effects; Affect; Alleles; Allelomorphs; Anti-Retroviral Agents; Antibodies; Antibody Formation; Antibody Production; Antibody Response; Antiretroviral Agents; Antiretroviral Therapy, Highly Active; Applications Grants; Assay; Bioassay; Biologic Assays; Biological Assay; Blood Plasma; Blotting, Western; C-C CKR-5 Gene; C-C Chemokine Receptor Type 5 Gene; CC-CKR-5 Gene; CCCKR5 Gene; CCR-5 Gene; CCR5; CCR5 gene; CD195 Antigen Gene; CHEMR13 Gene; CKR-5 Gene; CKR5 Gene; CMKBR5 Gene; CTL; California; Caring; Cell-Mediated Lympholytic Cells; Characteristics; Chemokine (C-C) Receptor 5 Gene; Clinic; Clinical; Co-culture; Cocultivation; Coculture; Coculture Techniques; Communicable Diseases; Competence; Cytolytic T-Cell; Cytotoxic T Cell; Cytotoxic T-Lymphocytes; DNA; Data; Defective Hybrids; Defective Interfering Particles; Defective Interfering Viruses; Defective Viruses; Deoxyribonucleic Acid; Detection; Drugs; Equilibrium; Evolution; FLR; Failure (biologic function); Gene Products, RNA; Genetic; Genetic Alteration; Genetic Change; Genetic Risk; Genetic defect; Genotype; Goals; Grant; Grant Proposals; Grants, Applications; HAART; HIV; HIV Antibodies; HIV Infections; HIV antibody positive; HIV-1; HIV-1 Fusion Co-Receptor Gene; HIV-Associated Antibodies; HIV-I; HIV1; HTLV-III; HTLV-III Antibodies; HTLV-III Infections; HTLV-III-LAV Antibodies; HTLV-III-LAV Infections; Haplotypes; Highly Active Antiretroviral Therapy; Host Factor; Host Factor 1; Host Factor 1 Protein; Host Factor Protein; Host Factor Q; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human immunodeficiency virus 1; Human, Adult; Immunodeficiency Virus Type 1, Human; Immunologist; Immunology; Immunology (Including BRMP); Immunology (NCI Program); Incomplete Viruses; Individual; Infection; Infectious Disease Epidemiology; Infectious Disease Pathway; Infectious Diseases; Infectious Diseases and Manifestations; Infectious Disorder; Infectious Epidemiology; Integration Host Factors; Investigators; K23 Award; K23 Mechanism; K23 Program; Knowledge; LAV Antibodies; LAV-HTLV-III; Living Costs; Logistic Regressions; Lymphadenopathy-Associated Antibodies; Lymphadenopathy-Associated Virus; Measures; Medical; Medication; Mentored Patient-Oriented Research Career Development Award; Mentored Patient-Oriented Research Career Development Award (K23); Mentors; Methods; Minority; Modeling; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Mutation; NIH; National Institutes of Health; National Institutes of Health (U.S.); Optics; Pathogenesis; Patients; Pharmaceutic Preparations; Pharmaceutical Preparations; Phenotype; Plasma; Prevalence; Publishing; RNA; RNA, Non-Polyadenylated; Recovery; Regression Analyses; Regression Analysis; Regression Diagnostics; Regressions, Logistic; Reporting; Research; Research Personnel; Researchers; Reticuloendothelial System, Serum, Plasma; Ribonucleic Acid; Risk; Role; Sample Size; San Francisco; Series; Serologic; Serological; Serum, Plasma; Statistical Regression; T-Cells; T-Lymphocyte; T-Lymphocytes, Cytotoxic; T-Lymphotropic Virus Type III Antibodies, Human; T-Lymphotropic Virus Type III Infections, Human; Testing; Thymus-Dependent Lymphocytes; Time; Toxic effect; Toxicities; Translational Research; Translational Research Enterprise; Translational Science; Transmission; Treatment Side Effects; United States National Institutes of Health; Universities; Vaccine Design; Variant; Variation; Viral; Viremia; Virus; Virus-HIV; Viruses, General; Western Blotting; Western Blottings; Western Immunoblotting; adult human (21+); anti-retroviral; anti-retroviral therapy, highly active; antibody biosynthesis; antiretroviral; antiretroviral therapy; balance; balance function; base; career; clinical phenotype; cohort; comparison group; density; drug/agent; experiment; experimental research; experimental study; failure; genome mutation; hfq Gene Product; human T cell leukemia virus III; human T lymphotropic virus III; immunoglobulin biosynthesis; insight; novel; novel therapeutic intervention; patient centered; patient oriented; prevent; preventing; protective effect; protein blotting; public health relevance; research study; response; side effect; skills; social role; therapeutic vaccine; therapy adverse effect; thymus derived lymphocyte; translation research enterprise; transmission process; treatment adverse effect; treatment strategy; viraemia; viral sepsis; virusemia
Project start date: 2007-06-15
Project end date: 2012-05-31
Budget start date: 1-JUN-2009
Budget end date: 31-MAY-2010
PFA/PA: PA-05-143
5K23AI075985-03 (2009): $125820
Sponsored Links Excellgen http://Excellgen.com
VIROLOGIC AND HOST FACTORS CONTRIBUTING TO HIV CONTROL IN ELITE CONTROLLERS
Hiroyu Hatano
University Of California San Francisco, 3333 California St., Ste 315, San Francisco, Ca 94143-0962
Grant 5K23AI075985-04 from National Institute Of Allergy And Infectious Diseases
Abstract: This is an application for a K23 award for Dr. Hiroyu Hatano, a fellow in adult infectious diseases at the University of California, San Francisco who is establishing herself as a young investigator in patient-oriented translational research of HIV-infected elite controllers. Elite controllers are HIV-antibody individuals who have maintained "undetectable" plasma HIV-1 RNA levels in the absence of antiretroviral therapy. This K23 award will provide Dr. Hatano with the support necessary to accomplish the following goals (1) to recover, quantify, and characterize HIV in elite controllers; (2) to examine the interactions between host and virologic factors that contribute to effective virologic control in elite controllers; and (4) to develop an independent, clinic-based translational research career. To achieve these goals, Dr. Hatano has assembled a mentoring team comprised of her primary mentor, Dr. Steven G. Deeks, an expert in translational HIV research with a focus on HIV pathogenesis, and three co-mentors Dr. Joseph K. Wong, a clinical virologist and expert in HIV latency; Dr. Joseph (Mike) McCune, an immunologist with expertise in the immunology of HIV infection; and Dr. Jeffrey N. Martin, an expert in infectious diseases and epidemiology. Although highly active antiretroviral therapy (HAART) has been effective in decreasing the morbidity and mortality associated with HIV infection for patients with access to medical care, the challenges of long-term efficacy, toxicity, cost, and life-long adherence remain. Thus, models of eradication need to be examined in order to elucidate potential host and viral factors that may make eradication possible. One such model is the elite controller cohort. Although rare, elite controllers provide a unique opportunity to study a naturally occurring model of sustained control of HIV. Dr. Hatano will identify both virologic factors (Aim 1) and host factors (and their interactions) (Aim 2) that contribute to the effective control of HIV in elite controllers, and she will examine whether a proportion of them have "cleared" their HIV infection (Aim 3). This research will provide Dr. Hatano with the skills and preliminary data to successfully compete for R34 (Year 4) and U01 (Year 5) NIH grant support that will focus specifically on HIV latency and control of HIV in elite controllers and whether treatment with HAART or others methods aimed at depletion of HIV can eradicate HIV in elite controllers. Insight into how elite controllers maintain their distinctive version of HIV latency and durable viral control may affect HIV treatment strategies, bolster therapeutic vaccine design efforts, and contribute to the possible eradication of HIV
Keywords: 21+ years old; AIDS Antibodies; AIDS Virus; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Acute; Adherence; Adherence (attribute); Adult; Adverse effects; Affect; Alleles; Allelomorphs; Anti-Retroviral Agents; Antibodies; Antibody Formation; Antibody Production; Antibody Response; Antiretroviral Agents; Antiretroviral Therapy, Highly Active; Applications Grants; Assay; Bioassay; Biologic Assays; Biological Assay; Blood Plasma; Blotting, Western; C-C CKR-5 Gene; C-C Chemokine Receptor Type 5 Gene; CC-CKR-5 Gene; CCCKR5 Gene; CCR-5 Gene; CCR5; CCR5 gene; CD195 Antigen Gene; CHEMR13 Gene; CKR-5 Gene; CKR5 Gene; CMKBR5 Gene; CTL; California; Caring; Cell-Mediated Lympholytic Cells; Characteristics; Chemokine (C-C) Receptor 5 Gene; Clinic; Clinical; Co-culture; Cocultivation; Coculture; Coculture Techniques; Communicable Diseases; Competence; Cytolytic T-Cell; Cytotoxic T Cell; Cytotoxic T-Lymphocytes; DNA; Data; Defective Hybrids; Defective Interfering Particles; Defective Interfering Viruses; Defective Viruses; Deoxyribonucleic Acid; Detection; Drugs; Equilibrium; Evolution; FLR; Failure (biologic function); Gene Products, RNA; Genetic; Genetic Alteration; Genetic Change; Genetic Risk; Genetic defect; Genotype; Goals; Grant; Grant Proposals; Grants, Applications; HAART; HIV; HIV Antibodies; HIV Infections; HIV antibody positive; HIV-1; HIV-1 Fusion Co-Receptor Gene; HIV-Associated Antibodies; HIV-I; HIV1; HTLV-III; HTLV-III Antibodies; HTLV-III Infections; HTLV-III-LAV Antibodies; HTLV-III-LAV Infections; Haplotypes; Highly Active Antiretroviral Therapy; Host Factor; Host Factor 1; Host Factor 1 Protein; Host Factor Protein; Host Factor Q; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human immunodeficiency virus 1; Human, Adult; Immunodeficiency Virus Type 1, Human; Immunologist; Immunology; Immunology (Including BRMP); Immunology (NCI Program); Incomplete Viruses; Individual; Infection; Infectious Disease Epidemiology; Infectious Disease Pathway; Infectious Diseases; Infectious Diseases and Manifestations; Infectious Disorder; Infectious Epidemiology; Integration Host Factors; Investigators; K23 Award; K23 Mechanism; K23 Program; Knowledge; LAV Antibodies; LAV-HTLV-III; Living Costs; Logistic Regressions; Lymphadenopathy-Associated Antibodies; Lymphadenopathy-Associated Virus; Measures; Medical; Medication; Mentored Patient-Oriented Research Career Development Award; Mentored Patient-Oriented Research Career Development Award (K23); Mentors; Methods; Minority; Modeling; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Mutation; NIH; National Institutes of Health; National Institutes of Health (U.S.); Optics; Pathogenesis; Patients; Pharmaceutic Preparations; Pharmaceutical Preparations; Phenotype; Plasma; Prevalence; Publishing; RNA; RNA, Non-Polyadenylated; Recovery; Regression Analyses; Regression Analysis; Regression Diagnostics; Reporting; Research; Research Personnel; Researchers; Reticuloendothelial System, Serum, Plasma; Ribonucleic Acid; Risk; Role; Sample Size; San Francisco; Series; Serologic; Serological; Serum, Plasma; Statistical Regression; T cell response; T-Lymphocytes, Cytotoxic; T-Lymphotropic Virus Type III Antibodies, Human; T-Lymphotropic Virus Type III Infections, Human; Testing; Time; Toxic effect; Toxicities; Translational Research; Translational Research Enterprise; Translational Science; Transmission; Treatment Side Effects; United States National Institutes of Health; Universities; Vaccine Design; Variant; Variation; Viral; Viremia; Virus; Virus-HIV; Viruses, General; Western Blotting; Western Blottings; Western Immunoblotting; adult human (21+); anti-retroviral; anti-retroviral therapy, highly active; antibody biosynthesis; antiretroviral; antiretroviral therapy; balance; balance function; base; career; clinical phenotype; cohort; comparison group; density; drug/agent; experiment; experimental research; experimental study; failure; genome mutation; hfq Gene Product; human T cell leukemia virus III; human T lymphotropic virus III; immunoglobulin biosynthesis; insight; novel; novel therapeutic intervention; patient centered; patient oriented; prevent; preventing; protective effect; protein blotting; public health relevance; research study; side effect; skills; social role; therapeutic vaccine; therapy adverse effect; translation research enterprise; transmission process; treatment adverse effect; treatment strategy; viraemia; viral sepsis; virusemia
Project start date: 2007-06-15
Project end date: 2012-05-31
Budget start date: 1-JUN-2010
Budget end date: 31-MAY-2011
PFA/PA: PA-05-143
5K23AI075985-04 (2010): $125820
Grants awarded to Hiroyu Hatano
Virologic And Host Factors Contributing To HIV Control In Elite Controllers
Hiroyu Hatano
University Of California San Francisco 3333 California St., Ste 315 San Francisco, Ca 941430962
Grant 1K23AI075985-01 from National Institute Of Allergy And Infectious Diseases IRG: AIDS
Abstract: This is an application for a K23 award for Dr. Hiroyu Hatano, a fellow in adult infectious diseases at the University of California, San Francisco who is establishing herself as a young investigator in patient-oriented translational research of HIV-infected elite controllers. Elite controllers are HIV-antibody individuals who have maintained "undetectable" plasma HIV-1 RNA levels in the absence of antiretroviral therapy. This K23 award will provide Dr. Hatano with the support necessary to accomplish the following goals (1) to recover, quantify, and characterize HIV in elite controllers; (2) to examine the interactions between host and virologic factors that contribute to effective virologic control in elite controllers; and (4) to develop an independent, clinic-based translational research career. To achieve these goals, Dr. Hatano has assembled a mentoring team comprised of her primary mentor, Dr. Steven G. Deeks, an expert in translational HIV research with a focus on HIV pathogenesis, and three co-mentors Dr. Joseph K. Wong, a clinical virologist and expert in HIV latency; Dr. Joseph (Mike) McCune, an immunologist with expertise in the immunology of HIV infection; and Dr. Jeffrey N. Martin, an expert in infectious diseases and epidemiology. Although highly active antiretroviral therapy (HAART) has been effective in decreasing the morbidity and mortality associated with HIV infection for patients with access to medical care, the challenges of long-term efficacy, toxicity, cost, and life-long adherence remain. Thus, models of eradication need to be examined in order to elucidate potential host and viral factors that may make eradication possible. One such model is the elite controller cohort. Although rare, elite controllers provide a unique opportunity to study a naturally occurring model of sustained control of HIV. Dr. Hatano will identify both virologic factors (Aim 1) and host factors (and their interactions) (Aim 2) that contribute to the effective control of HIV in elite controllers, and she will examine whether a proportion of them have "cleared" their HIV infection (Aim 3). This research will provide Dr. Hatano with the skills and preliminary data to successfully compete for R34 (Year 4) and U01 (Year 5) NIH grant support that will focus specifically on HIV latency and control of HIV in elite controllers and whether treatment with HAART or others methods aimed at depletion of HIV can eradicate HIV in elite controllers. Public health relevance Insight into how elite controllers maintain their distinctive version of HIV latency and durable viral control may affect HIV treatment strategies, bolster therapeutic vaccine design efforts, and contribute to the possible eradication of HIV.
Keywords: RNA, virus, AIDS, AIDS education /prevention, DNA, HAART (highly active antiretroviral therapy), HIV infection, allele, amidohydrolase, antibody, antibody titering, balance, base, career, cell, communicable disease, copying, culture, cytotoxic T lymphocyte, defective virus, density, emotion, epidemiology, evolution, experimental design, gene, gene mutation, genetics, genotype, immunology, infection, information system, insight, latent virus infection, lead, learning, measurement, medicine, model, patient oriented research, phenotype, plasma, plasma cell, public health, role, sectioning, success, suppression, therapy, training, university, vaccine, virus load, virus replication, western blotting, clinical research
Project start date: 2007-06-15
Project end date: 2012-05-31
1K23AI075985-01 (2007): $124200