New Dual Combination of Dolutegravir-Rilpivirine for Switching to Maintenance Antiretroviral Therapy

AIDS Rev. 2018;20(4):179-186. doi: 10.24875/AIDSRev.M18000026.

Abstract

Advances in antiretroviral therapy have led to dramatic improvements in survival of HIV-infected persons. However, HIV cure remains elusive and lifelong treatment is needed. Attempts for reducing long-term drug exposure, toxicities, and cost, while maintaining viral suppression, have led to explore whether maintenance strategies with less than triple therapy could be feasible using the newest more potent antiretrovirals. While monotherapies have failed to do so with selection of drug resistance, some dual combinations have proven its efficacy when used sequentially in patients with viral suppression under standard triple regimens. Furthermore, the advent of coformulations makes easier long-term drug adherence. Herein, we review the current experience with the new single tablet regimen of dolutegravir (DTG) and rilpivirine (RPV) (Juluca®). It is the first approved two-drug single-tablet regimen and the first dual nuc-sparing coformulation. Two randomized, non-inferiority clinical trials (SWORD-1 and -2) and five observational studies have evaluated DTG-RPV in treatment-experienced patients. Despite distinct inclusion criteria, more than 95% of patients kept plasma HIV-RNA undetectable for at least 48 weeks. Along with virological efficacy being non-inferior to triple regimens, the tolerance of DTG-RPV was good, being discontinuations due to adverse events only 0.8-7.9%. Moreover, improvements were seen in lipid profiles in patients switched from protease inhibitors, and in renal and bone biomarkers in those switched from tenofovir disoproxil fumarate. Finally, resistance is rare failing on DTG-RPV. In summary, DTG-RPV is a novel two-drug coformulation that can be effectively and safely used in treatment-experienced patients with viral suppression if the virus is fully susceptible to both drugs. Its unique features make this drug one of the best options as long-term regimen or lifelong maintenance HIV therapy.

Keywords: Adverse events; Dolutegravir; Drug resistance; Long-term regimens; Maintenance; Rilpivirine; Switch; Toxicity; Two-drug regimens.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Antiretroviral Therapy, Highly Active / methods*
  • Drug Combinations
  • Drug Resistance, Viral
  • Drug Substitution / methods*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • HIV Infections / drug therapy*
  • Heterocyclic Compounds, 3-Ring / administration & dosage*
  • Humans
  • Maintenance Chemotherapy / methods*
  • Observational Studies as Topic
  • Oxazines
  • Piperazines
  • Pyridones
  • Randomized Controlled Trials as Topic
  • Rilpivirine / administration & dosage*
  • Sustained Virologic Response
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Drug Combinations
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir
  • Rilpivirine