Low-dose ritonavir-boosted darunavir in virologically suppressed HIV-1-infected adults: an open-label trial (ANRS 165 Darulight)

J Antimicrob Chemother. 2018 Aug 1;73(8):2129-2136. doi: 10.1093/jac/dky181.

Abstract

Objectives: To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs.

Design: A multicentre, Phase II, non-comparative, single-arm, open-label study.

Setting: Tertiary care hospitals in France.

Subjects: One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs.

Primary outcome measure: Proportion of patients with treatment success: plasma HIV RNA level ≤50 copies/mL up to 48 weeks without any change in the study regimen, in a modified ITT (mITT) analysis.

Results: At baseline, most patients were male (78%), with a median age of 43 years, median duration of HIV RNA ≤50 copies/mL of 35 months and median CD4 T cell count of 633 cells/mm3. Seventy-six percent received tenofovir/emtricitabine and 24% abacavir/lamivudine. Five patients were excluded from the mITT analysis. The rate of treatment success through to week 48 was 91.6% (87/95; 95% CI 84.1%-96.3%). No RAM was detected in three amplifiable genotypes. A total of 212 adverse events (AEs) occurred in 64 patients (64%); 9 AEs were serious, none leading to treatment discontinuation.

Conclusions: In HIV-infected patients well suppressed with darunavir/r (800/100 mg) and two NRTIs, a reduction of the darunavir dose to 400 mg/day maintained virological efficacy and was safe over 48 weeks.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Darunavir / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / administration & dosage*
  • Treatment Outcome
  • Viral Load

Substances

  • HIV Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Ritonavir
  • Darunavir