title: A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
abstract: BACKGROUND
  We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.
  
  
  METHODS
  The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses.
  
  
  RESULTS
  Overall, at therapy start, 27% of patients had FPR ≤ 10 (6%, FPR ≤ 2; 7%, FPR 2-5; 14%, FPR 5-10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%.
  
  
  CONCLUSIONS
  Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Armenia
authors.affiliation: Unité Mixte de Recherche en Santé (UMR_S) 1136 Pierre Louis Institute of Epidemiology and Public Health, Université Pierre et Marie Curie (UPMC) University Paris 06, Paris, France; UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France; Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié Salpêtrière, Paris, France.
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulie
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Di Carlo
authors.affiliation: Antiviral Drug Monitoring Unit, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fabeni
authors.affiliation: Antiviral Drug Monitoring Unit, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Gori
authors.affiliation: Antiviral Drug Monitoring Unit, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; Molecular Virology, University Hospital Tor Vergata, Rome, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.affiliation: Infectious Disease Unit, University Hospital Tor Vergata, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Sarmati
authors.affiliation: Department of Infectious Dermatology, San Gallicano Hospital, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: Department of Infectious Dermatology, San Gallicano Hospital, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Latini
authors.affiliation: Infectious Diseases Division, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Evangelo
authors.initials: E
authors.lastname: Boumis
authors.affiliation: Infectious Diseases Division, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.affiliation: Infectious Diseases Division, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Bellagamba
authors.affiliation: Infectious Disease Unit, University Hospital Tor Vergata, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.affiliation: Unité Mixte de Recherche en Santé (UMR_S) 1136 Pierre Louis Institute of Epidemiology and Public Health, Université Pierre et Marie Curie (UPMC) University Paris 06, Paris, France; UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France; Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié Salpêtrière, Paris, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Unité Mixte de Recherche en Santé (UMR_S) 1136 Pierre Louis Institute of Epidemiology and Public Health, Université Pierre et Marie Curie (UPMC) University Paris 06, Paris, France; UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France; Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe hospitalier Pitié Salpêtrière, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.affiliation: Infectious Diseases Division, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; Antiviral Drug Monitoring Unit, Istituto Nazionale delle Malattie Infettive (INMI) Lazzaro Spallanzani, Rome, Italy; Molecular Virology, University Hospital Tor Vergata, Rome, Italy.
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Perno
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Santoro
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents