loading page

The Presence of Resistance-associated Mutations in Reverse Transcriptase Gene is Associated with Cerebrospinal Fluid HIV-1 Escape: a multicentric retrospective analysis
  • +10
  • Mattia Trunfio,
  • Carmela Pinnetti,
  • Stefania Arsuffi,
  • Francesca Bai,
  • Luigi Celani,
  • Gabriella D'Ettorre,
  • Jaime Vera H,
  • Antonella Darminio,
  • Emanuele Focà,
  • Valeria Ghisetti,
  • stefano bonora,
  • Andrea Antinori,
  • Andrea Calcagno
Mattia Trunfio
Amedeo di Savoia Hospital at Department of Medical Sciences

Corresponding Author:mattia.trunfio@edu.unito.it

Author Profile
Carmela Pinnetti
INMI Lazzaro Spallanzani IRCCS
Author Profile
Stefania Arsuffi
Universita degli Studi di Brescia Dipartimento di Scienze Cliniche e Sperimentali
Author Profile
Francesca Bai
Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo
Author Profile
Luigi Celani
Umberto I Policlinico di Roma
Author Profile
Gabriella D'Ettorre
Umberto I Policlinico di Roma
Author Profile
Jaime Vera H
Brighton and Sussex Medical School Department of Global Health and Infection
Author Profile
Antonella Darminio
Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo
Author Profile
Emanuele Focà
Universita degli Studi di Brescia Dipartimento di Scienze Cliniche e Sperimentali
Author Profile
Valeria Ghisetti
ASL Citta di Torino
Author Profile
stefano bonora
Amedeo di Savoia Hospital at Department of Medical Sciences
Author Profile
Andrea Antinori
INMI Lazzaro Spallanzani IRCCS
Author Profile
Andrea Calcagno
Amedeo di Savoia Hospital at Department of Medical Sciences
Author Profile

Abstract

Background: We assessed whether the association between the risk of cerebrospinal fluid escape (CVE) and specific antiretroviral (ARV) classes, such as protease inhibitors, is due to suboptimal pharmacological profile generated by archived resistance-associated mutations (RAMs). Methods: A retrospective multicentric study on 300 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modelling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modelling the risk. Results: Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/μL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs 32.1%, p=0.005) and CSF RAMs in RT (n=63, 57.1% vs 28.6%, p=0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p<0.001) and in models restricted to plasma viral load ≤50 copies/mL (n=202; aOR 4.3 , p=0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (p<0.001). Conclusions: Viruses harboring mutations appear to favor CVE and the impact of single ARV classes or type of ART regimens may lose significance when adjusted for the presence and effect of specific RAMs.
29 Dec 2022Submitted to Journal of Medical Virology
29 Dec 2022Submission Checks Completed
29 Dec 2022Assigned to Editor
29 Dec 2022Review(s) Completed, Editorial Evaluation Pending
02 Jan 2023Reviewer(s) Assigned
04 Feb 2023Editorial Decision: Revise Major
07 Feb 20231st Revision Received
08 Feb 2023Review(s) Completed, Editorial Evaluation Pending
08 Feb 2023Submission Checks Completed
08 Feb 2023Assigned to Editor
11 Feb 2023Reviewer(s) Assigned
23 Mar 2023Editorial Decision: Accept