The overall purpose of the Clinical Data and Sample Core (Clinical Core) is to provide relevant clinical datato Project 1, 'Computational and Bioinformatics modeling and analysis of HIV Protease drug resistance', anddata and specimens to Project 4, 'Structure-based Mechanisms for Resistance to PR Inhibitors'.Clinical experience often differs from that of controlled clinical trials, and the evolution of resistance toprotease inhibitor drugs (Pis) seen in clinical settings may differ that selected in vitro or in the homogenouspopulations in randomized trials. This may be particularly true with respect to highly treatment-experiencedindividuals with persistent virological failure. We hypothesize that modeling limited data sets from clinicalcohort(s) will lead to new predictions concerning evolution of resistance that can in turn be tested inlaboratory models. Similarly, it is hypothesized that both unique patterns of mutations within the HIVprotease as well as compensatory mutations outside the protease region may correlate with success orfailure of PI containing regimens,and that specific strains from clinical trial samples can be identified to testthis hypothesis in vitro.;Specifically, the Clinical Core will: (1) Implement human use projects to obtain and abstract limited data setssuitable for modeling and/or other analysis by Project 1 which include HIV genotypic (sequence as well asinterpretation) data, immunologic (T-cell subset), virological (HIV RNA), and treatment (sequential treatmentregimen) from three clinical sites in Southern California and a 'salvage' trial in highly advanced patients(Options in Managment with Antiretrovirals - OPTIMA, substudy), and (2) Identify and characterize (PCRamplifcation and sequencing of gag-pol) samples from clinical trials (OPTIMA substudy, Drug Adherence inHIV-infected Veterans) likely to contain suitable mutations for study by Project 4.
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