Transmitted Drug Resistance to Integrase-Based First-Line Human Immunodeficiency Virus Antiretroviral Regimens in Mediterranean Europe

Clin Infect Dis. 2023 May 3;76(9):1628-1635. doi: 10.1093/cid/ciac972.

Abstract

Background: We evaluated the prevalence of transmitted drug resistance (TDR) to integrase strand-transfer inhibitors (INSTIs) and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and of clinically relevant resistance (CRR) in newly diagnosed people with human immunodeficiency virus (HIV; PWH) naive to antiretroviral therapy (ART) in Europe.

Methods: MeditRes is a consortium that includes ART-naive PWH newly diagnosed in France, Greece, Italy, Portugal, and Spain during 2018-2021. Reverse transcriptase and INSTI sequences were provided by participating centers. To evaluate the prevalence of surveillance drug resistance mutations (SDRM), we used the calibrated population resistance tools from the Stanford HIV website. To evaluate CRR, defined as any resistance level ≥3, we used the Stanford HIV Drug Resistance Database v.9.1 algorithm.

Results: We included 2705 PWH, 72% men, median age of 37 years (interquartile range, 30-48); 43.7% were infected by non-B subtypes. The prevalence of INSTI-SDRMs was 0.30% (T66I, T66A, E92Q, E138T, E138K, Y143R, S147G, R263K; all n=1) and the prevalence of NRTI-SDRMs was 5.77% (M184V: 0.85%; M184I: 0.18%; K65R/N: 0.11%; K70E: 0.07%; L74V/I: 0.18%; any thymidine analog mutations: 4.36%). INSTI-CRR was 2.33% (0.15% dolutegravir/bictegravir, 2.29% raltegravir/elvitegravir) and 1.74% to first-line NRTIs (0.89% tenofovir/tenofovir alafenamide, 1.74% abacavir, 1.07% lamivudine/emtricitabine).

Conclusions: We present the most recent data on TDR to integrase-based first-line regimens in Europe. Given the low prevalence of CRR to second-generation integrase inhibitors and to first-line NRTIs during 2018-2021, it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second-generation integrase inhibitors.

Keywords: HIV; resistance; transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Drug Resistance, Viral / genetics
  • Europe / epidemiology
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • HIV Integrase Inhibitors* / pharmacology
  • HIV Integrase Inhibitors* / therapeutic use
  • HIV Integrase* / genetics
  • HIV-1* / genetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Integrases / genetics
  • Male
  • Mutation
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Integrases
  • HIV Integrase Inhibitors
  • Anti-Retroviral Agents
  • Reverse Transcriptase Inhibitors
  • Adenine
  • HIV Integrase
  • Heterocyclic Compounds, 3-Ring