Week 96 efficacy of lopinavir/ritonavir monotherapy in virologically suppressed patients with HIV: a randomized non-inferiority trial (ANRS 140 DREAM)

J Antimicrob Chemother. 2018 Jun 1;73(6):1672-1676. doi: 10.1093/jac/dky055.

Abstract

Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection.

Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years.

Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death.

Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred.

Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.

Publication types

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

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Female
  • Frankreich
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Hospitals, University
  • Humans
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / therapeutic use*
  • Viral Load / drug effects*

Substances

  • Anti-Retroviral Agents
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Ritonavir