Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine

Viruses. 2024 Oct 31;16(11):1715. doi: 10.3390/v16111715.

Abstract

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).

Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.

Results: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S.

Conclusions: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.

Keywords: HIV-1 drug resistance; non-nucleoside reverse transcriptase inhibitors; rilpivirine.

MeSH terms

  • Adult
  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Drug Resistance, Viral* / genetics
  • Female
  • Genotype
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV Reverse Transcriptase* / genetics
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Reverse Transcriptase Inhibitors* / pharmacology
  • Reverse Transcriptase Inhibitors* / therapeutic use
  • Rilpivirine* / therapeutic use

Substances

  • Rilpivirine
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • Anti-HIV Agents
  • reverse transcriptase, Human immunodeficiency virus 1