Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I

J Antimicrob Chemother. 2019 Dec 1;74(12):3555-3564. doi: 10.1093/jac/dkz347.

Abstract

Objectives: Studies 1878 and 1844 demonstrated non-inferior efficacy of switching suppressed HIV-1-infected adults to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus continuing boosted PI-based triple regimens or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Here, detailed analyses of pre-existing resistance in the two BIC/FTC/TAF switch studies and efficacy at week 48 are described.

Methods: Pre-existing resistance was assessed from historical genotypes (documented resistance to study drugs was excluded) and by retrospective baseline proviral archive DNA genotyping from whole blood. Outcomes were based on HIV-1 RNA at week 48 with missing values imputed using the last on-treatment observation carried forward method.

Results: Cumulative pre-existing resistance data from historical and proviral genotypes were obtained for 95% (543/570) of participants who switched to BIC/FTC/TAF. Altogether, 40% (217/543) had one or more pre-existing primary resistance substitutions in protease, reverse transcriptase and/or integrase. Pre-switch NRTI resistance was detected in 16% (89/543) of BIC/FTC/TAF-treated participants, with M184V or M184I detected by proviral genotyping in 10% (54/543). At week 48, 98% (561/570) of all BIC/FTC/TAF-treated participants versus 98% (213/217) with pre-existing resistance and 96% (52/54) with archived M184V/I had HIV-1 RNA <50 copies/mL. No BIC/FTC/TAF-treated participants developed treatment-emergent resistance to study drugs.

Conclusions: Pre-existing resistance substitutions, notably M184V/I, were unexpectedly common among suppressed participants who switched to BIC/FTC/TAF. High rates of virological suppression were maintained in the overall study population and in those with pre-existing resistance, including M184V/I, for up to 48 weeks of BIC/FTC/TAF treatment with no resistance development. These results indicate that BIC/FTC/TAF is an effective treatment option for suppressed patients, including those with evidence of archived NRTI resistance.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Amino Acid Substitution / genetics
  • Anti-HIV Agents / therapeutic use*
  • Double-Blind Method
  • Drug Resistance, Multiple, Viral / genetics
  • Drug Substitution*
  • Drug Therapy, Combination
  • Emtricitabine / therapeutic use*
  • Genotype
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Humans
  • RNA, Viral / blood
  • Retrospective Studies
  • Sustained Virologic Response*

Substances

  • Anti-HIV Agents
  • Heterocyclic Compounds, 4 or More Rings
  • RNA, Viral
  • bictegravir
  • tenofovir alafenamide
  • Emtricitabine
  • Adenine