Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study

Abstract

BackgroundDual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection.MethodsWe retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis.ResultsFour hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6–97.2) without M184V and 87.8% (95% CI, 78.4–97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51–199 copies/mL) was 79.8% (95% CI, 67.8%–91.8%) with M184V vs 90.1% (95% CI, 84.0%–96.2%) without M184V (P = .016).ConclusionsPrevious selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.

Lamivudine‐based maintenance antiretroviral therapies in patients living with HIV‐1 with suppressed HIV RNA: derivation of a predictive score for virological failure

“…As previously reported [5], the M184V mutation was not associated with VF. However, historical genotype could still be useful when deciding whether to simplify ART, as a consequence of the high risk of VF in patients with RAMs other than M184V.…”

“…Despite their high efficacy, based on previous experience with nucleoside reverse transcriptase inhibitor (NRTI)-reducing strategies, some patients on two-drug regimens could be at higher risk of virological failure (VF); for instance, those with a shorter time of virological suppression [5]. Also, when considering simplification to NRTI-sparing regimens, a lower CD4 count nadir, longer antiretroviral (ARV) exposure, lower adherence and higher residual viraemia were also predictive of VF [6]: although this was not demonstrated in previous trials with two-drug regimens, it could still represent a concern in this group in the long term.…”

Long-term data on the efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multi-centre cohort of HIV-1-infected, virologically suppressed patients

“…24 Our study also allows to frame the target of patients for whom this switch strategy may results more advantageous; in particular our data confirm that, even with a longer follow-up, the lone presence of the M184V resistance mutation is not a predictor of virological failure for this 3TC-containing dual regimen, probably because of the reduced replicative fitness caused to the virus by this mutation. [25][26][27] However, as previously reported by Gagliardini et al, 28 the M184V mutation appears to be associated with virological failure in patients with a reduced time of virological suppression at baseline. These results must bring to the attention of the clinician the need to collect a precise clinical and virological history of the patient before implementing a therapeutic simplification towards a two-drug regimen.…”

Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China

“…The elevated presence of M184V/I is expected and arises as a consequence of the use of 3TC as part of all the firstline regimens in China [23]. Although M184V/I causes high-level in vitro resistance to 3TC, M184V/I is not a contraindication to continued treatment with 3TC because it increases susceptibility to AZT, and in addition, it is associated with clinically significant reductions in HIV-1 replication [14,24,25]. Similar to our study finding, a high prevalence of M184 V/I mutation has been reported in Asia, Sub-Saharan Africa and Latin America, but a lower prevalence in western Europe [26][27][28][29][30][31].…”