Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial)
| Autor: | Marie-Laure Nere, Sinata Koulla-Shiro, Adrien Sawadogo, Jacques Reynes, Sabrina Eymard-Duvernay, Mireille Mpoudi Ngolle, Cheik Tidiane Ndour, Alix Armero, Constance Delaugerre, Marie-Laure Chaix, Anrs, Laura Ciaffi, Ali Amara, Ndaye Fatou Ngom Gueye |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Oncology medicine.medical_specialty Anti-HIV Agents 030106 microbiology HIV Infections Deep sequencing Defective virus 03 medical and health sciences 0302 clinical medicine Internal medicine Drug Resistance Viral medicine Humans Protease Inhibitors Pharmacology (medical) Protease inhibitor (pharmacology) 030212 general & internal medicine Pharmacology business.industry High-Throughput Nucleotide Sequencing Lamivudine Viral Load Resistance mutation Virological failure Stop codon Infectious Diseases Mutation Mutation (genetic algorithm) HIV-1 business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 76:1286-1293 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | BackgroundThe ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation.ObjectivesWe aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF).MethodsUltra-deep sequencing (UDS) was performed on proviral HIV-DNA at inclusion among 265 patients enrolled in the ANRS 12026/MOBIDIP trial, and on plasma from 31 patients experiencing VF. The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models.ResultsM184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. M184I mutation was always associated with a STOP codon, suggesting defective virus. The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively.ConclusionsUsing UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. The antiviral efficacy of lamivudine-based dual therapy regimens is mainly due to the residual lamivudine activity. |
| Databáze: | OpenAIRE |
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