1. 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 6 th 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? REFERRAL TO SMMC INITIATION OF ART (n=306) SEQUENCE #1SEQUENCE #2 RNA #1RNA #2 vEvol, GSS, DRMs Mean VL n=75 patients; t=11 months

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!