title: 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.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.affiliation: University of Rome Tor Vergata, Rome, Italy. Electronic address: santormaria@gmail.com.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Santoro
authors.affiliation: University of Rome Tor Vergata, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Armenia
authors.affiliation: Modena University Hospital, Modena, Italy.
authors.forename: Vanni
authors.initials: V
authors.lastname: Borghi
authors.affiliation: Modena University Hospital, Modena, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Gennari
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Gori
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.affiliation: University of Rome Tor Vergata, Rome, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fabeni
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannetti
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cicalini
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Bellagamba
authors.affiliation: University Hospital Tor Vergata, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.affiliation: La Sapienza University, Polo Pontino, Latina, Italy.
authors.forename: Claudio Maria
authors.initials: CM
authors.lastname: Mastroianni
authors.affiliation: Modena University Hospital, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000235:genetics*; D024882:Drug Resistance, Viral; D005260:Female; D060005:Genotyping Techniques / Q000379:methods*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D008875:Middle Aged; D009154:Mutation; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral
keywords: HIV reservoir; HIV-DNA; PBMC resistance; Proviral DNA; Resistance genotyping; Resistance mutations