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Scientific article
English

A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure

Published inInternational journal of antimicrobial agents, vol. 42, no. 1, p. 42-47
Publication date2013
Abstract

This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.

Keywords
  • Anti-HIV Agents/therapeutic use
  • Antiretroviral Therapy, Highly Active/methods
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Drug Resistance, Viral
  • Female
  • HIV Infections/drug therapy/virology
  • HIV-1/genetics/isolation & purification
  • Humans
  • Male
  • Mutation, Missense
  • Pyrrolidinones/therapeutic use
  • RNA, Viral/blood
  • Treatment Failure
  • Viral Load
Citation (ISO format)
MARCELIN, Anne-Geneviève et al. A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure. In: International journal of antimicrobial agents, 2013, vol. 42, n° 1, p. 42–47. doi: 10.1016/j.ijantimicag.2013.02.016
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Article (Published version)
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Identifiers
ISSN of the journal0924-8579
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