Regimen selection in the OPTIONS trial of HIV salvage therapy: drug resistance, prior therapy, and race-ethnicity determine the degree of regimen complexity

HIV Clin Trials. 2015 Aug;16(4):147-56. doi: 10.1179/1945577115Y.0000000001. Epub 2015 Jul 27.

Abstract

Background: Regimen selection for highly treatment-experienced patients is complicated.

Methods: Using a web-based utility, study team members reviewed antiretroviral (ARV) history and resistance data and recommended individual ARV regimens and nucleoside reverse transcriptase inhibitor (NRTI) options for treatment-experienced participants consisting of 3-4 of the following agents: raltegravir (RAL), darunavir (DRV)/ritonavir, tipranavir (TPV)/ritonavir, etravirine (ETR), maraviroc (MVC), and enfuvirtide (ENF). We evaluated team recommendations and site selection of regimen and NRTIs. Associations between baseline factors and the selection of a complex regimen (defined as including four ARV agents or ENF) were explored with logistic regression.

Results: A total of 413 participants entered the study. Participants initiated the first or second recommended regimen 86% of the time and 21% of participants started a complex regimen. In a multivariable model, ARV resistance to NRTI (odds ratio [OR] = 2.2), non-nucleoside reverse transcriptase inhibitor (NNRTI, OR = 6.2) or boosted protease inhibitor (PI, OR = 6.6), prior use of integrase strand transfer inhibitor (INSTI, OR = 25), and race-ethnicity (all P ≤ 0.01) were associated with selection of a complex regimen. Black non-Hispanic (OR = 0.5) and Hispanic participants from the continental US (OR = 0.2) were less likely to start a complex regimen, compared to white non-Hispanics.

Conclusions: In this multi-center trial, we developed a web-based utility that facilitated treatment recommendations for highly treatment-experienced patients. Drug resistance, prior INSTI use, and race-ethnicity were key factors in decisions to select a more complex regimen.

Keywords: Antiretroviral therapy; HIV drug resistance,; Phenotypic susceptibility score,; Treatment-experienced,; Tropism,; cPSS,.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Anti-Retroviral Agents / therapeutic use*
  • Darunavir / therapeutic use
  • Drug Resistance, Viral
  • Enfuvirtide
  • Female
  • HIV Envelope Protein gp41 / therapeutic use
  • HIV Infections / drug therapy*
  • HIV Infections / ethnology
  • HIV Infections / virology
  • Humans
  • Male
  • Middle Aged
  • Nitriles
  • Peptide Fragments / therapeutic use
  • Pyridazines / therapeutic use
  • Pyrimidines
  • Raltegravir Potassium / therapeutic use
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / therapeutic use
  • Salvage Therapy*

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • HIV Envelope Protein gp41
  • Nitriles
  • Peptide Fragments
  • Pyridazines
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • etravirine
  • Enfuvirtide
  • Raltegravir Potassium
  • Ritonavir
  • Darunavir