Genotypic resistance test in proviral DNA can identify resistance mutations never detected in historical genotypic test in patients with low level or undetectable HIV-RNA

Mauro Zaccarelli, Maria Mercedes Santoro, Daniele Armenia, Vanni Borghi, William Gennari, Caterina Gori, Federica Forbici, Ada Bertoli, Lavinia Fabeni, Alberto Giannetti, Stefania Cicalini, Rita Bellagamba, Massimo Andreoni, Claudio Maria Mastroianni, Cristina Mussini, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Andrea Antinori

Research output: Contribution to journalArticle

Abstract

Background Beyond the detection of resistant HIV strains found in plasma samples, archival HIV-DNA in peripheral blood mononuclear cells (PBMCs) might represent a reservoir of additional resistance. Objective To characterize the HIV-1 resistance in PBMCs from patients with suppressed or low-level viremia (50–1000 copies/mL) and evaluate its added value compared to the resistance detected in previous plasma genotypic resistance tests (GRTs). Study design HIV-1 infected patients selected for treatment change despite low/undetectable viremia were tested. Number and type of primary resistance mutations (PRMs) detected in PBMCs were compared to those detected in previous plasma GRTs. Logistic regression assessed factors associated with presence of at least one PRM in PBMCs. Result 468 patients with a PBMC GRT were analyzed; 149 of them had at least 2 plasma GRTs performed before PBMC genotyping. 42.3% of patients showed at least one PRM in PBMCs. The highest proportion of PRMs in PBMCs was observed for NRTI class (30.6%), followed by NNRTI (22.2%), PI (14.1%) and INI (4.9%). In 20.1% of patients, PRMs were detected only in PBMCs and not in any of the plasma GRT previously performed. By using multivariable analysis, a higher number of previous regimens, injecting drug-use route and a lower nadir CD4 were associated with significantly higher risk of detecting PRMs in PBMCs. Conclusion Our findings support the usage of PBMC GRT in addition to the current recommended plasma RNA test, especially when therapeutic and/or resistance information is not available.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalJournal of Clinical Virology
Volume82
DOIs
Publication statusPublished - Sep 1 2016

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Keywords

  • HIV reservoir
  • HIV-DNA
  • PBMC resistance
  • Proviral DNA
  • Resistance genotyping
  • Resistance mutations

ASJC Scopus subject areas

  • Medicine(all)
  • Virology
  • Infectious Diseases

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