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, Arturo Ciccullo, Alberto Borghetti, Franco Maggiolo, Dario Bartolozzi, Vanni Borghi, Monica Pecorari, Antonio Di Biagio, Anna Paola Callegaro, Bianca Bruzzone, Francesco Saladini, Stefania Paolucci, Renato Maserati, Maurizio Zazzi, Simona Di Giambenedetto, Andrea De Luca

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalOpen Forum Infectious Diseases
Volume5
Issue number6
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Dual therapy
  • Integrase inhibitors
  • Lamivudine
  • M184V
  • NRTI mutations

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

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