Monitoring the emergence of resistance mutations in patients infected with HIV-1 under salvage therapy with raltegravir in Rio de Janeiro, Brazil: a follow-up study

J Med Virol. 2012 Dec;84(12):1869-75. doi: 10.1002/jmv.23409.

Abstract

The present study describes a follow-up of a prospective and observational cohort of patients infected with HIV-1 and treated with raltegravir for salvage therapy in Brazil. Two groups of patients were analyzed: switching from T20 to RAL (Group 1, n = 9) and salvage therapy containing RAL (Group 2, n = 10). Blood samples were drawn for CD4(+) T-cell counts and HIV-1 viral load determinations. Protease, reverse transcriptase, and integrase genotyping were performed at baseline and at the time of virologic failure. CD4(+) T-cells increased at 6 and 12 months in both groups; HIV-1 viral load was continuously suppressed for Group 1, and for Group 2 it significantly decreased after starting a RAL-containing regimen. Three out of 10 patients from Group 2 could not suppress HIV-1 viral load. The mutations Q148H + G140S were observed for two patients and for the third patient only mutations to PR/RT inhibitors were detected. The genotypic sensitivity score (GSS) was analyzed for all patients of Group 2 and both patients who developed resistance to raltegravir presented a GSS < 2.0 for the RAL-containing scheme, which could be associated to the lack of effectiveness of the proposed scheme. The present study describes, for the first time in Brazil, the close follow-up of a series of patients using a raltegravir-containing HAART, showing the safety of the enfuvirtide switch to RAL and the effectiveness of a therapeutic regimen with RAL in promoting immune reconstitution and suppressing HIV replication, as well as documenting the occurrence of resistance to integrase inhibitors in the country.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Brazil / epidemiology
  • CD4 Lymphocyte Count
  • Cyclohexanes / therapeutic use
  • Drug Resistance, Viral / genetics*
  • Enfuvirtide
  • Follow-Up Studies
  • Genotyping Techniques
  • HIV Envelope Protein gp41 / therapeutic use
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • HIV Integrase / genetics
  • HIV Protease / genetics
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • Humans
  • Maraviroc
  • Mutation
  • Peptide Fragments / therapeutic use
  • Prospective Studies
  • Pyrrolidinones / therapeutic use*
  • RNA, Viral / blood
  • Raltegravir Potassium
  • Salvage Therapy / methods*
  • Treatment Outcome
  • Triazoles / therapeutic use
  • Viral Load
  • Virus Replication

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Pyrrolidinones
  • RNA, Viral
  • Triazoles
  • Enfuvirtide
  • Raltegravir Potassium
  • HIV Integrase
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • HIV Protease
  • Maraviroc