Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. (20th August 2021)

• Record Type: Journal Article
• Authors: Palich, Romain; Teyssou, Elisa; Sayon, Sophie; Abdi, Basma; Soulie, Cathia; Cuzin, Lise; Tubiana, Roland; Valantin, Marc-Antoine; Schneider, Luminita; Seang, Sophie; Wirden, Marc; Pourcher, Valérie; Katlama, Christine; Calvez, Vincent; Marcelin, Anne-Geneviève
• Is Part Of: Journal of infectious diseases. Volume 225:Number 3(2022)
• Page Start: 502
• Page End: 509
• Publication Date: 2021-08-20
• Subjects: antiretroviral treatment -- HIV -- HIV reservoir -- M184V -- ultradeep sequencing; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab413
• Languages: English
• ISSNs: 0022-1899

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. Abstract : An ultrasensitive sequencing technique showed that the M184V mutation progressively cleared in the HIV DNA reservoir over time in virally suppressed HIV patients. However, this mutation was likely to persist in patients with sustained past replication under lamivudine or emtricitabine.