Doravirine/islatravir for the treatment of HIV

Expert Opin Pharmacother. 2025 Jan;26(1):9-15. doi: 10.1080/14656566.2024.2440000. Epub 2024 Dec 10.

Abstract

Introduction: HIV is a global disease affecting millions of people. While treatments have improved over the past decades, treatment failure remains a significant issue for treatment experienced patients. Doravirine/islatravir is a new dual-therapy regimen with a promising resistance profile and reductions in central nervous system effects. Recent trials have shown non-inferiority compared to current standards of care. However, current research suggests that CD4 counts decrease in an islatravir-dose dependent manner, but more data is needed to determine the full extent of this effect at lower doses.

Areas covered: Doravirine/islatravir is a therapeutic combination for the treatment of HIV which is currently in Phase 3 trials. This article reviews key studies regarding the safety and efficacy of the combination.

Expert opinion: When approved, doravirine/islatravir should be considered for patients who have previously failed treatment due to viral resistance. It expands the selection of two-drug single-pill therapies and introduces a novel mechanism of action to the market. However, more data is needed regarding the effects of islatravir on CD4 counts. ISL doses as low as 0.25 mg proved non-inferior to current treatments. Therefore, evaluation of the long-term efficacy and safety of DOR/ISL should focus on reduced doses of ISL and minimizing CD4 reduction.

Keywords: HIV; doravirine; islatravir; non-nucleoside reverse transcriptase inhibitor; nucleoside reverse transcriptase translocation inhibitor.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • CD4 Lymphocyte Count
  • Deoxyadenosines
  • Dose-Response Relationship, Drug
  • Drug Combinations*
  • Drug Resistance, Viral*
  • HIV Infections* / drug therapy
  • Humans
  • Nitriles / therapeutic use
  • Pyridones* / administration & dosage
  • Pyridones* / pharmacology
  • Pyridones* / therapeutic use
  • Triazoles* / administration & dosage
  • Triazoles* / therapeutic use

Substances

  • doravirine
  • Anti-HIV Agents
  • Pyridones
  • Triazoles
  • Drug Combinations
  • islatravir
  • Nitriles
  • Deoxyadenosines