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). (24th February 2021)

• Record Type: Journal Article
• Authors: Delaugerre, Constance; Nere, Marie-Laure; Eymard-Duvernay, Sabrina; Armero, Alix; Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien; Ngom Gueye, Ndaye Fatou; Ndour, Cheik Tidiane; Mpoudi Ngolle, Mireille; Amara, Ali; Chaix, Marie-Laure; Reynes, Jacques
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 76:Number 5(2021)
• Page Start: 1286
• Page End: 1293
• Publication Date: 2021-02-24
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkab002
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: The 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. Objectives: We aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF). Methods: Ultra-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. Results: M184V 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. Conclusions: Using 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.