Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing.

PloS One
Max LatailladeMichael J Kozal

Abstract

It is unknown whether HIV-positive patients experiencing virologic failure (VF) on boosted-PI (PI/r) regimens without drug resistant mutations (DRM) by standard genotyping harbor low-level PI resistant variants. CASTLE compared the efficacy of atazanavir/ritonavir (ATV/r) with lopinavir/ritonavir (LPV/r), each in combination with TVD in ARV-naïve subjects. To determine if VF on an initial PI/r-based regimen possess low-level resistant variants that may affect a subsequent PI-containing regimen. Patients experiencing VF on a Tenofovir/Emtricitabine+PI/r regimen were evaluated by ultra deep sequencing (UDS) for mutations classified/weighted by Stanford HIVdb. Samples were evaluated for variants to 0.4% levels. 36 VF subjects were evaluated by UDS; 24 had UDS for PI and RT DRMs. Of these 24, 19 (79.2%) had any DRM by UDS. The most common UDS-detected DRM were NRTI in 18 subjects: M184V/I (11), TAMs(7) & K65R(4); PI DRMs were detected in 9 subjects: M46I/V(5), F53L(2), I50V(1), D30N(1), and N88S(1). The remaining 12 subjects, all with VLs<10,000, had protease gene UDS, and 4 had low-level PI DRMs: F53L(2), L76V(1), I54S(1), G73S(1). Overall, 3/36(8.3%) subjects had DRMs identified with Stanford-HIVdb weights >12 for ATV or LPV: N88...Continue Reading

References

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Citations

Mar 4, 2014·Current Infectious Disease Reports·Richard M GibsonMiguel E Quiñones-Mateu
May 14, 2014·Annual Review of Genomics and Human Genetics·Shiven B ChabriaMichael J Kozal
Mar 1, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jonathan Z Li, Daniel R Kuritzkes
Oct 8, 2013·PloS One·Brendan B LarsenJames I Mullins
Aug 6, 2015·AIDS·Maria CasadellàUNKNOWN ADVANZ and ADVANZ-3 Investigators
Mar 11, 2015·The Journal of Antimicrobial Chemotherapy·Charlotte CharpentierDiane Descamps
Dec 6, 2017·The Journal of Infectious Diseases·Natalia Stella-AscarizJonathan Z Li
Jan 4, 2013·Journal of Clinical Microbiology·Boaz AvidorDan Turner
Oct 21, 2021·Microbiology Spectrum·Horeyah Sarkhouh, Wassim Chehadeh

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Methods Mentioned

BETA
genotyping
Assay

Clinical Trials Mentioned

NCT00272779

Software Mentioned

CASTLE

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