Despite increasing use of integrase inhibitors to treat HIV infection, resistance to this class remains stable

J Antimicrob Chemother. 2026 Jan 6;81(1):dkaf454. doi: 10.1093/jac/dkaf454.

Abstract

Background: The aim of this study was to evaluate changes in prevalence of resistance to integrase strand transfer inhibitors (INSTIs) in relation to changes in their use over 16 years in people living with HIV (PLWHIV) treated with antiretrovirals (ARVs) and in virological failure.

Materials and methods: We analysed the use of different INSTIs (for ≥3 months during the study year) in ARV-treated PLWHIV in an academic centre and the HIV INSTI resistance profiles in RNA in case of virological failure (2008-24; analysed using the ANRS-MIE algorithm v33).

Results: During the studied period (2008-24), INSTI use increased from 3.3% to 71.2%. Raltegravir use peaked at 21.5% in 2013 and then declined to 2.5% in 2024. Elvitegravir followed a similar trend, increasing to 15.7% in 2018 and then decreasing to 1.5% in 2024. Dolutegravir increased steadily from 6.3% in 2014 to 39.3% in 2023 and bictegravir from 2.0% in 2018 to 28.0% in 2024. Cabotegravir, first noted in 2020 (0.3%), will reach 3.8% in 2024. The proportion of patients with INSTI-resistant viruses was initially high for raltegravir (47.8% in 2008), before decreasing. By 2024, resistance was 2.7% for dolutegravir, cabotegravir and bictegravir, but remained higher for raltegravir (8.5%) and elvitegravir (9.8%).

Conclusions: Although the use of INSTIs has increased over time with differences in the duration of use, we did not observe a corresponding increase in the proportion of ARV-treated PLWHIV who experienced virological failure with INSTI-resistant viruses during the study period.

MeSH terms

  • Adult
  • Amides
  • Diketopiperazines
  • Dolutegravir
  • Drug Resistance, Viral*
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV Integrase Inhibitors* / pharmacology
  • HIV Integrase Inhibitors* / therapeutic use
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Naphthyridines
  • Oxazines
  • Piperazines
  • Pyridones / therapeutic use
  • Quinolones / therapeutic use
  • Raltegravir Potassium / therapeutic use
  • Treatment Failure
  • Viral Load

Substances

  • HIV Integrase Inhibitors
  • Pyridones
  • Raltegravir Potassium
  • Quinolones
  • Heterocyclic Compounds, 3-Ring
  • Piperazines
  • Oxazines
  • Naphthyridines
  • Amides
  • Diketopiperazines
  • Dolutegravir
  • elvitegravir
  • bictegravir
  • cabotegravir

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