Salvage therapy or simplification of salvage regimens with dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART-experienced subjects: an Italian cohort

Antivir Ther. 2017;22(3):257-262. doi: 10.3851/IMP3095. Epub 2016 Sep 23.

Abstract

Background: Dolutegravir plus darunavir provide a high genetic barrier to HIV-1 resistance and are suitable for simple salvage regimens.

Methods: All HIV-1-infected subjects treated with dolutegravir plus boosted darunavir dual therapy between March 2011 and September 2015 were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48.

Results: We enrolled 113 subjects. After week 24, one was lost at follow-up, one dropped out for grade 2 elevation of liver enzymes, one died from illicit drug abuse and one from cancer-related sepsis. The mean age was 51, 26.5% were female and 9.7% were non-Caucasian. Twenty had never experienced failure. A total of 99 had reverse-transcriptase (RT) mutations, 87 had protease inhibitor mutations and 12 had integrase strand transfer inhibitor (INSTI) mutations. Viraemic patients declined from baseline to week 24 from 43.4% to 6.2%, the remainder being due to high baseline viraemia or adherence issues. The proportion of subjects with viraemia 1-49 copies/ml remained at 20.4% while those in whom no virus was detected (NVD) increased from 36.3% to 73.5% by week 24. All the 47 subjects who had a 48-week follow-up had <50 copies/ml and 42 (89.4%) had NVD. 18 subjects had reduced sensitivity to darunavir (Stanford median score 15, range 15-40), but none rebounded, 6 having a 24-week and 7 a 48-week follow-up. The median variation in serum creatinine was -0.01 (range +0.2 to -0.21) mg/dl.

Conclusions: This dual regimen provides a simple salvage regimen and proved safe and effective in this cohort.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiretroviral Therapy, Highly Active
  • Cohort Studies
  • Darunavir / therapeutic use*
  • Drug Resistance, Viral
  • Drug Substitution
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Mutation
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral
  • Retreatment
  • Ritonavir / therapeutic use*
  • Salvage Therapy
  • Viral Load
  • Virus Replication / drug effects
  • Young Adult

Substances

  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral
  • dolutegravir
  • Ritonavir
  • Darunavir