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S. Dalai MSc , S. Sethi MSc , V. Levy MD, D. Israelski MD, D. Katzenstein MD

HIV-1 Evolution and Drug Resistance Among Patients Receiving ART in San Mateo County, California, 1997-2010. S. Dalai MSc , S. Sethi MSc , V. Levy MD, D. Israelski MD, D. Katzenstein MD Division of Infectious Disease Stanford University, USA Primary contact: sdalai@stanford.edu

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S. Dalai MSc , S. Sethi MSc , V. Levy MD, D. Israelski MD, D. Katzenstein MD

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  1. HIV-1 Evolution and Drug Resistance Among Patients Receiving ART in San Mateo County, California, 1997-2010 S. Dalai MSc, S. SethiMSc, V. Levy MD, D. Israelski MD, D. Katzenstein MD Division of Infectious Disease Stanford University, USA Primary contact: sdalai@stanford.edu 6th IAS Conference, Rome, Italy 18.07.2011

  2. Background and Methods • In a community public health treatment program 75/306 patients (25%) remained viremic on ART • Paired RT/protease sequences from 75 patients were analyzed to determine vEvol over a median time of 11 months using a best-fit nucleotide substitution model implemented in PAUP. • DRM and genotypic susceptibility score (GSS) were determined using HIVSEQ (Stanford Drug Resistance Database). DRMs were correlated using permutation testing to control for a false discovery rate. • Is HIV-1 viral evolutionary rate (vEvol) associated with drug class, drug resistance mutations (DRMs) and/or RNA VL? n=75 patients; t=11 months vEvol, GSS, DRMs Mean VL

  3. HIV-1 viral evolution is associated with increased RNA VL and presence of PI DRMs

  4. Greater viral evolution in patients with history of PI-exposure no PI no PI-exp

  5. Viral evolution is associated with reduced ARV susceptibility

  6. Correlated DRM pairs associated with increased viral evolution

  7. Conclusions • Repeat HIV-1 RNA genotyping in viremic Rx-experienced patients in San Mateo revealed RT/Pr DRMs in 75% and evolutionary changes in 90%. • Viral evolution is associated with higher RNA VL, exposure to PI drugs, the co-occurrence of specific DRMs, and reduced genotypic susceptibility to all ARV classes • Future analyses will characterize the complex interactions among evolutionary change, DRMs, and reduced drug susceptibility • We would like to thank the following: • Patients, physicians, and staff at San Mateo Medical Center • Stanford HIV Drug Resistance Database team; • The Howard Hughes Medical Institute, California HIV Research Program, the Soros Foundation, and the Stanford Medical Scientist Training Program for financial support THANK YOU!

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