Presentation Abstract

Session: 100-HIV-1 Drug Resistance
Sunday, Sep 18, 2011, 11:15 AM - 1:15 PM
Presentation Title: H2-800 - Significant Reductions in the Prevalence of Protease Inhibitor and 3-Class Resistance: Recent Trends in a Large HIV-1 Protease/Reverse Transcriptase Database
Location: Exhibit Hall F1
Poster Board Number: 290
Presentation Number: H2-800
Pres. Time: Sunday, Sep 18, 2011, 11:15 AM - 1:15 PM
Category: H1
Keywords: HIV-1 resistance 
Author(s): A. C. Paquet, Masters (MA or MS) - Statistician, M. Evans - Principal Bioinformatics Scientist, C. Petropoulos - VP R&D Virology, CSO (MGRM) / VP (LabCorp), J. Whitcomb - VP, Operations (MGRM) / VP (LabCorp), E. Coakley - Senior Director, Clinical Research Collaboration, L. Napolitano - Medical Director, M. Haddad - Associate Director, Bioinformatics/Biostatistics;
Monogram Biosciences, South San Francisco, CA.
Financial Disclosures:  A. C. Paquet,
Monogram Biosciences Role(s): Employee, Received: Salary.
M. Evans,
Monogram Biosciences Role(s): Employee, Received: Salary.
C. Petropoulos,
Monogram Biosciences Role(s): Employee, Received: Salary.
J. Whitcomb,
Monogram Biosciences Role(s): Employee, Received: Salary.
E. Coakley,
Monogram Biosciences Role(s): Employee, Received: Salary.
L. Napolitano,
Monogram Biosciences Role(s): Employee, Received: Salary.
M. Haddad,
Monogram Biosciences Role(s): Employee, Received: Salary.
Abstract: Background: Drug resistance testing for individuals infected with HIV-1 is a key component of the management of antiretroviral (ARV) therapy. We examined phenotypic drug resistance patterns in protease- (PI), nucleoside-reverse-transcriptase- (NRTI), and non-nucleoside-reverse-transcriptase-inhibitors (NNRTI) as well as 1-, 2-, and 3-class resistance over time by surveying Monogram Biosciences commercial database. Methods: Samples submitted for routine phenotypic and genotypic testing showing phenotypic resistance to at least one drug within PIs, NRTIs, and NNRTIs as measured by fold-change of IC50 (FC) ≥ lower cutoff (CO) were selected. A total of 68587 resistant samples collected from 2003 through 2010 were grouped into specimens that had FC ≥ CO for minimum of 1 drug in each drug class. Significance of these trends was evaluated using the Jonckheere-Terpstra test. Results: Among samples that showed any phenotypic drug resistance, prevalence of resistance to PIs decreased dramatically from 52% in 2003 to 26% in 2010. Frequency of NRTI and NNRTI resistance over the same period also decreased, from 77% to 70%, and 70% to 61%, respectively. Percentage of samples with 1-class resistance increased from 31% to 54% while 2-class resistance remained relatively stable (40% to 35%), and 3-class resistance declined from 29% to 11%. Within 2-class resistant samples collected in 2010, proportion of isolates resistant to NRTIs and NNRTIs was 70%, PIs and NRTIs 24%, and PIs and NNRTIs 7%; these proportions for 2003 samples were 54%, 37%, and 9% respectively. All trends in prevalence of resistance to PIs, NRTIs, NNRTIs, 1-, 2- and 3-class resistance were statistically significant (p-value < 0.05). Conclusions: A strong trend of decreasing prevalence of PI resistance was observed in Monogram commercial database between 2003 and 2010. This trend was accompanied by a significant reduction in the prevalence of 3-class resistance. These results may have important implications for ARV selection, clinical trial design and drug development.




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