High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I

AIDS. 2022 Sep 1;36(11):1511-1520. doi: 10.1097/QAD.0000000000003244. Epub 2022 Apr 23.

Abstract

Objective: We investigated the prevalence of preexisting M184V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

Design: Participant data were pooled from six clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed people with HIV.

Methods: Preexisting drug resistance was assessed by historical genotypes and/or baseline proviral DNA genotyping. Virologic outcomes were determined by last available on-treatment HIV-1 RNA. Stepwise selection identified potential risk factors for M184V/I in a multivariate logistic regression model.

Results: Altogether, 2034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data, and 1825 of these participants had baseline genotypic data available. Preexisting M184V/I was identified in 182 (10%), mostly by baseline proviral DNA genotype ( n = 167). Most substitutions were M184V ( n = 161) or M184V/I mixtures ( n = 10). Other resistance substitutions were often detected in addition to M184V/I ( n = 147). At last on-treatment visit, 98% (179/182) with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/ml, with no treatment-emergent resistance to B/F/TAF. Among adult participants, factors associated with preexisting M184V/I included other resistance, black race, Hispanic/Latinx ethnicity, lower baseline CD4 + cell count, advanced HIV disease, longer duration of antiretroviral therapy, and greater number of prior third agents.

Conclusion: M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Adult
  • Alanine
  • Amides
  • Anti-HIV Agents* / therapeutic use
  • Clinical Trials as Topic
  • Drug Combinations
  • Emtricitabine
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Heterocyclic Compounds, 3-Ring
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Piperazines
  • Pyridones
  • RNA / therapeutic use
  • Tenofovir / analogs & derivatives

Substances

  • Amides
  • Anti-HIV Agents
  • Drug Combinations
  • Heterocyclic Compounds, 3-Ring
  • Heterocyclic Compounds, 4 or More Rings
  • Piperazines
  • Pyridones
  • RNA
  • bictegravir
  • Tenofovir
  • tenofovir alafenamide
  • Emtricitabine
  • Adenine
  • Alanine