Background We aimed to assess the kinetics of drug-resistant viral variants (DRVs) harboring the M184V mutation in the proviral DNA of long-term virally suppressed patients, and factors associated with DRV persistence. Methods HIV-DNA from blood cells stored in 2019 and 2016 was sequenced using both Sanger and ultradeep sequencing (SS and UDS, with a detection threshold of 1%) in ART-treated patients with HIV-RNA <50 copies/mL for at least 5 years, with past M184V mutation documented in

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... NA. Results Among the 79 tested patients, by combining SS and UDS, the M184V was found to be absent in 26/79 (33%) patients (M184V- patients), and persisted in 53/79 (67%) (M184V+ patients). The M184V+ patients had a longer history of ART, a lower CD4 nadir and higher pretherapeutic HIV-RNA. Among the 37 patients with viral sequences assessed by UDS, the proportion of M184V+ DRVs significantly decreased between 2016 and 2019 (40% versus 14%, p=0.005). The persistence of M184V was associated with the duration and level of HIV-RNA replication under 3TC/FTC (p=0.0009 and p=0.009, respectively). Conclusion While it decreased over time in HIV-DNA, the M184V mutation was more frequently persistent in the HIV-DNA of more experienced patients with longer past replication under 3TC/FTC.