期刊
JOURNAL OF INFECTIOUS DISEASES
卷 225, 期 3, 页码 502-509出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab413
关键词
antiretroviral treatment; HIV; HIV reservoir; M184V; ultradeep sequencing
资金
- ViiV Healthcare
- French National Agency for Research on AIDS and Emerging Infectious Diseases (ANRS-MIE) [AC43]
The presence of drug-resistant viral variants (DRVs) with the M184V mutation decreases over time in HIV DNA, but it persists more frequently in patients with longer treatment experience and past replication under 3TC/FTC.
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.
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