A research program is proposed that will serve as the basis for mentoring beginning investigators in AIDS-related patient-oriented research. This proposal builds on existing resources of the Division of Infectious Diseases at the University of Colorado Health Sciences Center, including an NIH-funded AIDS Clinical Trials Unit, an Adult ACTG Virology Support Laboratory, the Colorado HIV-1 Medicine Training Program (funded by an Institutional AIDS Training Grant), and RO1-funded research of the applicant. Clinical and research fellows, as well as junior faculty, interested in pursuing careers in therapeutic AIDS clinical trials and translational virology will be mentored by the applicant. Course work in molecular biology, biostatistics, HIV-1 medicine, and the ethics of human research will be offered. The research component of this proposal is focused on clinical trials of HIV-1 therapeutics and drug resistance in HIV-1 infection. Ongoing patient-oriented research under the applicant's direction comprises an array of studies with the overall goal of understanding the mechanisms, clinical significance, and management of drug resistance in HIV- I infection. Specific research aims of this proposal are 1) to determine the relationship between drug resistance and treatment response in clinical trials of salvage therapy and treatment intensification conducted by the Adult ACTG.; 2) to compare the utility of genotypic and phenotypic approaches to drug resistance testing in the management antiretroviral therapy; and 3) To compare the relative fitness of HIV-1 carrying protease and reverse transcriptase genes from wild-type and drug-resistant clinical isolates using a novel recombinant virus assay. This research program provides a framework within which the applicant can mentor beginning clinical investigators in patient-oriented research focused on these critical issues in HIV-1 medicine.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24RR016482-05
Application #
6883224
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Wilde, David B
Project Start
2001-06-01
Project End
2006-06-30
Budget Start
2005-06-01
Budget End
2006-06-30
Support Year
5
Fiscal Year
2005
Total Cost
$97,754
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Marconi, Vincent C; Wu, Baohua; Hampton, Jane et al. (2013) Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic. AIDS Patient Care STDS 27:657-68
Li, Jonathan Z; Paredes, Roger; Ribaudo, Heather J et al. (2013) Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure. J Infect Dis 207:893-7
Sunpath, Henry; Wu, Baohua; Gordon, Michelle et al. (2012) High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. AIDS 26:1679-84
Henrich, Timothy J; Lewine, Nicolas R P; Lee, Sun-Hee et al. (2012) Differential use of CCR5 by HIV-1 clinical isolates resistant to small-molecule CCR5 antagonists. Antimicrob Agents Chemother 56:1931-5
Hatano, Hiroyu; Scherzer, Rebecca; Wu, Yuaner et al. (2012) A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection. J Acquir Immune Defic Syndr 61:317-25
Li, Jonathan Z; Christensen, Julie A; Wang, Hongying et al. (2012) Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption. J Acquir Immune Defic Syndr 61:19-22
Lin, Nina H; Becerril, Carlos; Giguel, Francoise et al. (2012) Env sequence determinants in CXCR4-using human immunodeficiency virus type-1 subtype C. Virology 433:296-307
Murphy, Richard A; Marconi, Vincent C; Gandhi, Rajesh T et al. (2012) Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa. PLoS One 7:e44793
Murphy, Richard A; Sunpath, Henry; Castilla, Carmen et al. (2012) Second-line antiretroviral therapy: long-term outcomes in South Africa. J Acquir Immune Defic Syndr 61:158-163
Putcharoen, Opass; Lee, Sun Hee; Henrich, Timothy J et al. (2012) HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug. J Virol 86:1119-28

Showing the most recent 10 out of 72 publications