Impact of pre-existent drug resistance on virological efficacy of single-tablet regimens in people living with HIV.


Journal

International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 07 06 2021
revised: 21 06 2022
accepted: 05 07 2022
pubmed: 13 7 2022
medline: 24 8 2022
entrez: 12 7 2022
Statut: ppublish

Résumé

Despite the wide use of single-tablet regimens (STRs), few real-life data are available regarding the impact of pre-existent drug resistance on virological failure (VF). We aimed to fill this gap by analysing a large cohort of individuals selected from the ARCA database. The impact on VF of pre-existent resistance-associated mutations (RAMs) and cumulative genotypic susceptibility score (cGSS) before STR start was evaluated through survival analysis. Potential emergence of resistance at VF was also evaluated. Overall, 3916 individuals were included, comprising 678 treatment-naïve (G1), 2309 treatment-experienced aviraemic (G2) and 929 viraemic (G3), of whom 65.2% were treated with a STR based on efavirenz (35.2%) or rilpivirine (30.0%). At 2 years after starting a STR, the overall probability of VF was 5.9% in G1, 8.7% in G2 and 20.8% in G3. No impact of pre-existent resistance on VF was found in G1. The probability of VF was higher in patients with cGSS < 3 (reduced susceptibility to at least one drug) than in those with cGSS = 3 (full susceptibility to STR drugs) both in G2 and G3. A higher probability of VF was also found in the presence of pre-existent M184V (alone or in combination with pre-existent thymidine analogue mutations). Among patients who failed STR, a significant emergence of RAMs was found only in those exposed to EFV/FTC/TDF in G3 (specifically K103N and M184V). Our results confirm a high efficacy of STRs in clinical settings. Pre-existent resistance appears to influence virological efficacy of STRs in treatment-experienced individuals (both aviraemic and viraemic).

Identifiants

pubmed: 35820534
pii: S0924-8579(22)00148-0
doi: 10.1016/j.ijantimicag.2022.106636
pii:
doi:

Substances chimiques

Anti-HIV Agents 0
Tablets 0
Tenofovir 99YXE507IL

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

106636

Informations de copyright

Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None declared.

Auteurs

Giulia Stella (G)

Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medical Sciences, Infectious and Tropical Diseases Unit, AOU Senese, Siena, Italy.

Lorenzo Volpicelli (L)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Domenico Di Carlo (DD)

CRC Pediatric "Romeo and Enrica Invernizzi", Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.

Ilaria Vicenti (I)

Department of Medical Biotechnologies, University of Siena, Siena, Italy.

Luigi Celani (L)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Franco Maggiolo (F)

Department of Infectious Diseases, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.

Anna Paola Callegaro (AP)

Department of Laboratory Medicine, ASST Papa Giovanni XXIII, Bergamo, Italy.

William Gennari (W)

Unit of Virology and Molecular Microbiology, University Hospital, Modena, Italy.

Daniela Francisci (D)

Clinical Infectious Diseases, University of Perugia, Perugia, Italy.

Francesca Lombardi (F)

Department of Safety and Bioethics, Infectious Diseases Section, Catholic University of the Sacred Heart, Rome, Italy.

Lorenzo Piermatteo (L)

Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy.

Antonia Bezenchek (A)

IPRO-InformaPRO S.r.l., Rome, Italy; EuResist Network GEIE, Rome, Italy.

Valeria Micheli (V)

Laboratory of Clinical Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco, L. Sacco University Hospital, Milan, Italy.

Barbara Rossetti (B)

Department of Medical Sciences, Infectious and Tropical Diseases Unit, AOU Senese, Siena, Italy.

Maria Mercedes Santoro (MM)

Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy. Electronic address: santormaria@gmail.com.

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Classifications MeSH