Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens

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Abstract

The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5-22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4 + T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase geneswere performed at baseline and after 1, 2, 3, 6, and 12months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range118-407,107) to+ T-cell counts remained unchanged (from 212 cells/ml, range 10-764 to 262 cells/μl, range 13-760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1month after initiating salvage HAART. Of note, the E→G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additionalmutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1month after initiating HAART salvage regimens. A newmutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated.

Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalJournal of Medical Virology
Volume82
Issue number1
DOIs
Publication statusPublished - Jan 2010

Fingerprint

Highly Active Antiretroviral Therapy
Mutation
Integrases
HIV-1
RNA
T-Lymphocytes
CD4 Lymphocyte Count
Raltegravir Potassium
Treatment Failure
Drug Resistance
Codon
Italy
Peptide Hydrolases
Cell Count

Keywords

  • Drug resistance
  • HIV
  • Integrase
  • Mutations
  • Raltegravir

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

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title = "Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens",
abstract = "The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5-22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4 + T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase geneswere performed at baseline and after 1, 2, 3, 6, and 12months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range118-407,107) to+ T-cell counts remained unchanged (from 212 cells/ml, range 10-764 to 262 cells/μl, range 13-760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3{\%}) patients as early as 1month after initiating salvage HAART. Of note, the E→G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additionalmutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1month after initiating HAART salvage regimens. A newmutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated.",
keywords = "Drug resistance, HIV, Integrase, Mutations, Raltegravir",
author = "Fausto Baldanti and Stefania Paolucci and Roberto Gulminetti and Micaela Brandolini and Giorgio Barbarini and Renato Maserati",
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T1 - Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens

AU - Baldanti, Fausto

AU - Paolucci, Stefania

AU - Gulminetti, Roberto

AU - Brandolini, Micaela

AU - Barbarini, Giorgio

AU - Maserati, Renato

PY - 2010/1

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N2 - The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5-22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4 + T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase geneswere performed at baseline and after 1, 2, 3, 6, and 12months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range118-407,107) to+ T-cell counts remained unchanged (from 212 cells/ml, range 10-764 to 262 cells/μl, range 13-760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1month after initiating salvage HAART. Of note, the E→G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additionalmutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1month after initiating HAART salvage regimens. A newmutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated.

AB - The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5-22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4 + T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase geneswere performed at baseline and after 1, 2, 3, 6, and 12months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range118-407,107) to+ T-cell counts remained unchanged (from 212 cells/ml, range 10-764 to 262 cells/μl, range 13-760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1month after initiating salvage HAART. Of note, the E→G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additionalmutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1month after initiating HAART salvage regimens. A newmutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated.

KW - Drug resistance

KW - HIV

KW - Integrase

KW - Mutations

KW - Raltegravir

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