Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients

Author:

Palich Romain12ORCID,Teyssou Elisa2,Sayon Sophie2,Abdi Basma2ORCID,Soulie Cathia2,Cuzin Lise34ORCID,Tubiana Roland1,Valantin Marc-Antoine1,Schneider Luminita1,Seang Sophie1,Wirden Marc2,Pourcher Valérie1ORCID,Katlama Christine1,Calvez Vincent2,Marcelin Anne-Geneviève2

Affiliation:

1. Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Pierre Louis Epidemiology and Public Health Institute, INSERM 1136, Paris, France

2. Sorbonne University, Virology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Pierre Louis Epidemiology and Public Health Institute, INSERM 1136, Paris, France

3. Centre d’Epidémiologie et de Recherche en Santé des Populations, Toulouse University, INSERM UMR1295, Université Paul Sabatier, Toulouse, France

4. Infectious Diseases Department, Martinique University Hospital, Fort-de-France, MartiniqueFrance

Abstract

Abstract Background We aimed to assess the kinetics of drug-resistant viral variants (DRVs) harboring the M184V mutation in proviral DNA of long-term virally suppressed patients, and factors associated with DRV persistence. Methods Human immunodeficiency virus (HIV) DNA from blood cells stored in 2016 and 2019 was sequenced using Sanger and ultradeep sequencing (SS and UDS; detection threshold 1%) in antiretroviral therapy (ART)-treated patients with HIV RNA < 50 copies/mL for at least 5 years, with past M184V mutation documented in HIV RNA. Results Among 79 patients, by combining SS and UDS, M184V was found to be absent in 26/79 (33%) patients and persistent in 53/79 (67%). M184V-positive patients had a longer history of ART, lower CD4 nadir, and higher pretherapeutic HIV RNA. Among 37 patients with viral sequences assessed by UDS, the proportion of M184V-positive DRVs significantly decreased between 2016 and 2019 (40% vs 14%, P = .005). The persistence of M184V was associated with duration and level of HIV RNA replication under lamivudine/emtricitabine (3TC/FTC; P = .0009 and P = .009, respectively). Conclusions While it decreased over time in HIV DNA, M184V mutation was more frequently persistent in HIV DNA of more treatment-experienced patients with longer past replication under 3TC/FTC.

Funder

ViiV Healthcare

French National Agency for Research on AIDS and Emerging Infectious Diseases

ANRS-MIE

AC43)

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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