Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus

J Antimicrob Chemother. 2018 Jan 1;73(1):177-182. doi: 10.1093/jac/dkx371.

Abstract

Objectives: This study evaluated the virological efficacy of dolutegravir 50 mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data from clinical practice.

Patients and methods: This analysis included HIV-1-infected patients who were ≥18 years of age, treatment experienced, had HIV-1 RNA >50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50 mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www.progettoprestigio.it). Follow-up accrued from the start of dolutegravir 50 mg twice daily + OBT until virological failure (VF) or dolutegravir discontinuation for any reason or the last treatment visit on dolutegravir 50 mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA <50 copies/mL by 6 months and thereafter, or the occurrence of two consecutive HIV-1 RNA ≥50 copies/mL after achievement of undetectable viral load.

Results: The estimated VF probabilities were 17% (95% CI = 12%-24%), 28% (95% CI = 21%-37%), 33% (95% CI = 25%-43%), 39% (95% CI = 29%-51%) and 52% (95% CI = 39%-67%) at 12, 24, 36, 48 and 60 months since baseline, respectively. A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with ≥1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015).

Conclusions: Our data showed a favourable long-term efficacy of dolutegravir 50 mg twice daily in association with OBT in treatment-experienced failing subjects, with INSTI-resistant virus, in the real world. A close monitoring of adherence is crucial for maintenance of virological response in this fragile subgroup of subjects.

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Coinfection
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Integrase / genetics
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Hepatitis C, Chronic / drug therapy
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Pyridones
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir
  • HIV Integrase