Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation

HIV Med. 2020 May;21(5):309-321. doi: 10.1111/hiv.12829. Epub 2020 Jan 11.

Abstract

Objectives: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes.

Methods: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics.

Results: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11).

Conclusions: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

Keywords: HIV; M184I; M184V; emtricitabine; lamivudine.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacology
  • Drug Resistance, Viral / drug effects*
  • Drug Therapy, Combination
  • Emtricitabine / administration & dosage*
  • Emtricitabine / pharmacology
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Lamivudine / administration & dosage*
  • Lamivudine / pharmacology
  • Male
  • Mutation
  • Tenofovir / administration & dosage*
  • Tenofovir / pharmacology
  • Treatment Failure
  • United Kingdom

Substances

  • Anti-HIV Agents
  • Lamivudine
  • Tenofovir
  • Emtricitabine