Back to Search
Start Over
Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2015 Nov; Vol. 70 (11), pp. 3080-6. Date of Electronic Publication: 2015 Aug 26. - Publication Year :
- 2015
-
Abstract
- Objectives: The aim of this study was to characterize the prevalence and patterns of genotypic integrase inhibitor (INI) resistance in relation to HIV-1 clade.<br />Methods: The cohort comprised 533 INI-naive subjects and 255 raltegravir recipients with viraemia who underwent integrase sequencing in routine care across Europe, including 134/533 (25.1%) and 46/255 (18.0%), respectively, with non-B clades (A, C, D, F, G, CRF01, CRF02, other CRFs, complex).<br />Results: No major INI resistance-associated mutations (RAMs) occurred in INI-naive subjects. Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K + G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%). In addition, four (1.6%) raltegravir recipients showed novel mutations at recognized resistance sites (E92A, S147I, N155D, N155Q) and novel mutations at other integrase positions that were statistically associated with raltegravir exposure (K159Q/R, I161L/M/T/V, E170A/G). Comparing subtype B with non-B clades, Q148H/R/K occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005). Intermediate- to high-level cross-resistance to twice-daily dolutegravir was predicted in 40/255 (15.7%) subjects, more commonly in subtype B versus non-B clades (39/209, 18.7% versus 1/46, 2.2%; P = 0.003). A glycine (G) to serine (S) substitution at integrase position 140 required one nucleotide change in subtype B and two nucleotide changes in all non-B clades.<br />Conclusions: No major INI resistance mutations occurred in INI-naive subjects. Reduced occurrence of Q148H/R/K + G140S/A was seen in non-B clades versus subtype B, and was explained by the higher genetic barrier to the G140S mutation observed in all non-B clades analysed.<br /> (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
- Subjects :
- Anti-HIV Agents therapeutic use
Cohort Studies
Europe
Genotype
HIV-1 classification
HIV-1 isolation & purification
Humans
Integrase Inhibitors therapeutic use
Mutation, Missense
Raltegravir Potassium therapeutic use
Anti-HIV Agents pharmacology
Drug Resistance, Viral
HIV Infections drug therapy
HIV Infections virology
HIV-1 genetics
Integrase Inhibitors pharmacology
Raltegravir Potassium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 70
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 26311843
- Full Text :
- https://doi.org/10.1093/jac/dkv243