Content area
Full text
About the Authors:
Max Lataillade
* E-mail: [email protected]
Affiliations Research and Development, Bristol-Myers Squibb, Wallingford, Connecticut, United States of America, Yale University School of Medicine and Veterans Affairs Health Care Systems, New Haven, Connecticut, United States of America
Jennifer Chiarella
Affiliation: Yale University School of Medicine and Veterans Affairs Health Care Systems, New Haven, Connecticut, United States of America
Rong Yang
Affiliation: Research and Development, Bristol-Myers Squibb, Wallingford, Connecticut, United States of America
Michelle DeGrosky
Affiliation: Research and Development, Bristol-Myers Squibb, Wallingford, Connecticut, United States of America
Jonathan Uy
Affiliation: Research and Development, Bristol-Myers Squibb, Plainsboro, New Jersey, United States of America
Daniel Seekins
Affiliation: Research and Development, Bristol-Myers Squibb, Plainsboro, New Jersey, United States of America
Birgitte Simen
Affiliation: 454 Life Sciences-Roche Co., Branford, Connecticut, United States of America
Elizabeth St. John
Affiliation: 454 Life Sciences-Roche Co., Branford, Connecticut, United States of America
Elizabeth Moreno
Affiliation: 454 Life Sciences-Roche Co., Branford, Connecticut, United States of America
Michael Kozal
Affiliation: Yale University School of Medicine and Veterans Affairs Health Care Systems, New Haven, Connecticut, United States of America
Introduction
HIV treatment guidelines recommend combination antiretroviral (ARV) regimens for treatment naive patients consisting of a nucleoside/nucleotide reverse transcriptase inhibitor (N(t)RTI)-based backbone along with either a non-nucleoside reverse transcriptase inhibitor (NNRTI), an integrase inhibitor (INI) or a ritonavir (RTV)-boosted protease inhibitor (PI) [1]. At the end of 2009, 584,000 HIV positive patients under care were receiving ARVs in the USA [2]. Approximately 40% of patients were initiated on an N(t)RTI+RTV-boosted PI (PI/r) as a first line regimen [2].
The most common drug resistance mutation pattern by standard HIV genotyping in patients experiencing virologic failure on an initial regimen of Tenofovir/Emtricitabine (TDF/FTC) plus a ritonavir boosted protease inhibitor (PI/r) is a solitary reverse transcriptase (RT) M184V mutation or no resistance mutations [3]–[7]. It is not known if HIV patients on a PI/r regimen experiencing virologic failure without evidence of PI resistance mutations by standard genotyping harbor low-level PI-resistant variants that are below the detection levels of standard genotyping methods. Further, if low-level resistant variants exist in these patients, could they affect the use of a subsequent PI/r containing regimen?
The objective of this study was to determine if patients with virologic failure on an initial PI/r-based regimen without...