Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world

J Antimicrob Chemother. 2018 Jan 1;73(1):160-164. doi: 10.1093/jac/dkx348.

Abstract

Background: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern.

Objectives: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world.

Methods: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV. Blood samples were collected before and after 2 months of DAA treatment.

Results: One-hundred and thirty-seven patients were included: 21.2% treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (2D/3D) and 78.8% with sofosbuvir-based regimens. Suboptimal Ctrough before and during DAA was found, respectively, in 3 (10.3%) and 3 (10.3%) cases treated with 2D/3D, and 16 (14.8%) and 11 (10.2%) with sofosbuvir-based regimens, even if self-reported ARV adherence was always ≥93%. In 2D/3D-treated patients, median darunavir Ctrough during DAAs was significantly lower than observed before DAAs [1125 ng/mL (IQR, 810-1616) versus 1903 ng/mL (IQR 1387-3983), respectively] (n = 5; P = 0.009), with a 40.9% decrease. In the same group, no differences in atazanavir or raltegravir concentrations were found. In patients treated with sofosbuvir-based regimens, Ctrough of all ARVs were similar before and during DAAs.

Conclusions: In the real world of HIV/HCV coinfected patients, ARV plasma concentrations during DAAs were generally not different from those found before anti-HCV treatment. Although assessed in a small number of patients, darunavir concentrations during 2D/3D showed a significant reduction when compared with those found before DAAs. ARV plasma concentrations measurement during anti-HCV treatment may give useful information for managing HIV/HCV coinfected persons receiving treatment for both infections.

Publication types

  • Observational Study

MeSH terms

  • 2-Naphthylamine
  • Anilides / blood
  • Anilides / pharmacokinetics
  • Anilides / therapeutic use
  • Anti-Retroviral Agents* / blood
  • Anti-Retroviral Agents* / pharmacokinetics
  • Anti-Retroviral Agents* / therapeutic use
  • Carbamates / blood
  • Carbamates / pharmacokinetics
  • Carbamates / therapeutic use
  • Coinfection / drug therapy
  • Cyclopropanes
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Lactams, Macrocyclic
  • Macrocyclic Compounds / blood
  • Macrocyclic Compounds / pharmacokinetics
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Prospective Studies
  • Ritonavir / blood
  • Ritonavir / pharmacokinetics
  • Ritonavir / therapeutic use
  • Sofosbuvir / blood
  • Sofosbuvir / pharmacokinetics
  • Sofosbuvir / therapeutic use
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Uracil / analogs & derivatives
  • Uracil / blood
  • Uracil / pharmacokinetics
  • Uracil / therapeutic use
  • Valine

Substances

  • Anilides
  • Anti-Retroviral Agents
  • Carbamates
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Sulfonamides
  • ombitasvir
  • Uracil
  • Proline
  • 2-Naphthylamine
  • dasabuvir
  • Valine
  • Ritonavir
  • paritaprevir
  • Sofosbuvir