Long-term follow-up of HIV-1 multi-drug-resistant treatment-experienced participants treated with etravirine, raltegravir and boosted darunavir: towards drug-reduced regimen? ANRS CO3 Aquitaine Cohort 2007-2018

Int J Antimicrob Agents. 2023 Jan;61(1):106696. doi: 10.1016/j.ijantimicag.2022.106696. Epub 2022 Dec 2.

Abstract

Objective: To assess the efficacy of raltegravir, etravirine and darunavir/ritonavir (TRIO regimen) in treatment-experienced patients with human immunodeficiency virus-1 (HIV-1) infection by describing the proportion of patients who experienced virological failure (VF) at Week 24. The secondary objectives were to assess the HIV-1 plasma viral load (pVL) after Week 24, the proportion of patients who were receiving dual therapy or monotherapy at the last visit, and the number of deaths.

Methods: Patients from the ANRS CO3 Aquitaine Cohort who were prescribed the TRIO regimen between February 2007 and September 2018 were classified into two groups based on their pVL at study inclusion: the virological failure group (VFG; pVL >50 copies/mL) and the virologically suppressed group (VSG; pVL <50 copies/mL). The impact of baseline pVL and genotypic susceptibility score (GSS) on VF was analysed.

Results: In total, 184 patients were enrolled in this study, with 123 (66.8%) in the VFG and 61 (33.2%) in the VSG. The median length of follow-up was 7.5 (interquartile range 4.1-9.6) years, and 29 (15.8%) patients died. Thirty-seven (25.5%) patients experienced VF at Week 24, including 32/145 (32.7%) in the VFG and 5/47 (10.6%) in the VSG (P<0.01). Resistance-associated mutations were detected in integrase, reverse transcriptase and protease for 7/37 (18.9%), 3/37 (8.1%) and 1/37 (2.7%) patients, respectively. High pVL and GSS at baseline were independently associated with VF. At the last visit, 76/184 (41.3%) patients were still receiving the TRIO regimen, while 55/184 (29.9%) were receiving dual therapy and 1/184 (0.5%) was receiving protease inhibitor monotherapy. Among the 56 patients receiving dual therapy or monotherapy, 51 (96.2%) had pVL <50 copies/mL.

Conclusion: Despite a high level of mutation resistance at baseline, long-term virological follow-up was favourable and one-third of patients were eligible for drug-reducing strategies.

Keywords: Drug-reduced regimen; HIV; Heavily pre-treated patients; TRIO.

MeSH terms

  • Anti-HIV Agents*
  • Darunavir / therapeutic use
  • Drug Resistance, Viral
  • Follow-Up Studies
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Humans
  • Raltegravir Potassium / therapeutic use
  • Ritonavir / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

  • Raltegravir Potassium
  • Darunavir
  • etravirine
  • Anti-HIV Agents
  • Ritonavir