807. Limited Evolution of Inferred HIV-1 Tropism From R5 to Non-R5 While Viremia Is Undetectable During Standard HAART Therapy
Session: Abstracts: Oral Abstract Session: HIV Complications and Pathogenesis
Friday, October 22, 2010: 3:15 PM
118-120
Background:

CCR5 antagonists for HIV therapy require screening for plasma viral CCR5 use (“R5 tropism”).  However, many patients currently have undetectable HIV viremia, rendering it impossible to test plasma virus.  Here, we investigate changes from CCR5 to non-CCR5 tropic (or vice versa) after prolonged viral suppression on PI/NNRTI-based HAART regimens in the initially therapy-naive HOMER cohort from BC, Canada.

Methods:

Patients who experienced both post-treatment viral suppression (two consecutive viral loads < 500) and subsequent viral rebound (two consecutive dates with viral load >500) on HAART were included in this study (N=326).  Tropism was inferred from the gp-120 V3 loop genotype using the geno2pheno algorithm with a 5.75 cut-point. Original Trofile (Monogram) data was available on 24 patients.

Results:

Of the 281 patients with initially CCR5-tropic virus, 21 (7.4%) changed to non-CCR5-tropic over a median of 1.1 year (IQR 0.56-2.3 years) of undetectable viremia.  Explanatory models shows that each one log increase in viral load at baseline has an added risk of 2.66-fold for CCR5 to non-CCR5 tropism change, but neither the duration of undetectability nor the use of PI-based vs NNRTI-based HAART were predictors of tropism change.  15 patients were R5 by Trofile; only one changed to non-R5 (6.7%).  Of interest, a higher proportion (13 of 45 patients; 29%) changed tropism from non-R5 to R5 following undetectable viremia (Fisher’s Exact p<.001).

Conclusion:

Viral tropism inferred by genotype did not show significant evolution from R5 to non-R5 during prolonged periods of undetectable viral load during standard HAART therapy.  A higher viral load at baseline is associated with a higher probability of changing from CCR5 to non-CCR5 tropic HIV-1 at viral rebound.  This data supports the use of a previous R5 tropism result in patients with undetectable viremia who wish to consider a CCR5 antagontist.


Subject Category: H. HIV/AIDS and other retroviruses

Speakers:
Guinevere Q. Lee , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Winnie Dong , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Theresa Mo , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Chanson Brumme , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Conan Woods , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Steve Kanters , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Anya Shen , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Benita Yip , B.C. Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
Richard Harrigan, PhD , British Columbia Center for Excellence in HIV Research Labs, Vancouver, BC, Canada

Disclosures:

G. Q. Lee, None

W. Dong, None

T. Mo, None

C. Brumme, None

C. Woods, None

S. Kanters, None

A. Shen, Yes
BC Centre for Excellence in HIV/AIDS: Employee,

B. Yip, None

R. Harrigan, Yes
Pfizer: Consultant, Grant Investigator and Research Contractor,
Viiv: Consultant, Grant Investigator and Research Contractor,
Merck: Consultant and Grant Investigator,
Abbott: Grant Investigator,
Virco: Consultant,
Quest: Consultant,


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