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. 2018 May 15;5(6):ofy113.
doi: 10.1093/ofid/ofy113. eCollection 2018 Jun.

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

Roberta Gagliardini  1 , Arturo Ciccullo  2 , Alberto Borghetti  2 , Franco Maggiolo  3 , Dario Bartolozzi  4 , Vanni Borghi  5 , Monica Pecorari  6 , Antonio Di Biagio  7 , Anna Paola Callegaro  8 , Bianca Bruzzone  9 , Francesco Saladini  10 , Stefania Paolucci  11 , Renato Maserati  12 , Maurizio Zazzi  10 , Simona Di Giambenedetto  2 , Andrea De Luca  1   10 ; ARCA Study Group
Collaborators, Affiliations

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

Roberta Gagliardini et al. Open Forum Infect Dis. .

Abstract

Background: Dual 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.

Methods: We 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.

Results: Four 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).

Conclusions: Previous 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.

Keywords: M184V; NRTI mutations; dual therapy; integrase inhibitors; lamivudine.

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Figures

Figure 1.
Figure 1.
a: Estimated probability of being free from virological failure (VF) with dual therapy (M184V groups based on the hGRT). b: Estimated probability of being free from virological failure (VF) in the overall population of dual therapy and in patients with shorter time of viral suppression (M184V groups based on the hGRT). c: Estimated probability of being free from treatment discontinuation (TD) with dual therapy (M184V groups based on the hGRT). d: Estimated probability of being free from virological blips (VB) with dual therapy (M184V groups based on the hGRT).
See this image and copyright information in PMC

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