HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir

K. A. Sutherland, J. Ghosn, J. Gregson, Jean Mbisa, M. L. Chaix, I. Cohen codar, J. F. Delfraissy, C. Delaugerre, R. K. Gupta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Objective: PI susceptibility results from a complex interplay between protease and Gag proteins, with Gag showing wide variation across HIV-1 subtypes. We explored the impact of pre-treatment susceptibility on the outcome of lopinavir/ritonavir monotherapy. Methods: Treatment-naive individuals who experienced lopinavir/ritonavir monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) with those who achieved virological response ('successes'). Successes were defined by viral load <400 copies/mL after week 24 and <50 copies/mL from week 48 to week 96. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain. Results: Baseline lopinavir susceptibility was lower in viral failures compared with viral successes, but the differences were not statistically significant (median lopinavir susceptibility: 4.4 versus 8.5, respectively, P=0.17). Among CRF02_AG/G patients, there was a significant difference in lopinavir susceptibility between the two groups (7.1 versus 10.4, P=0.047), while in subtype B the difference was not significant (2.7 versus 3.4, P=0.13). Subtype CRF02_AG/G viruses had a median lopinavir FC of 8.7 compared with 3.1 for subtype B (P=0.001). Conclusions: We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on lopinavir/ritonavir monotherapy in antiretroviral-naive patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure.

Original languageEnglish
Pages (from-to)243-248
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015

Bibliographical note

Publisher Copyright:
© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Keywords

  • Antiretroviral therapy
  • Gag
  • Protease inhibitor
  • Resistance

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