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 MDDivision of Infectious Disease

Stanford University, USAPrimary contact: sdalai@stanford.edu

6th IAS Conference, Rome, Italy18.07.2011

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

INITIATIONOF ART (n=306)

SEQUENCE #1 SEQUENCE #2

RNA #1 RNA #2

vEvol, GSS, DRMs

Mean VL

n=75 patients; t=11 months

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

Greater viral evolution in patients with history of PI-exposure

no PI

no PI-exp

Viral evolution is associated with reduced ARV susceptibility

Correlated DRM pairs associated

with increased viral evolution

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!