TURQUOISE-I Part 1b: Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin for Hepatitis C Virus Infection in HIV-1 Coinfected Patients on Darunavir

J Infect Dis. 2017 Feb 15;215(4):599-605. doi: 10.1093/infdis/jiw597.

Abstract

Background: Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART).

Methods: Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks.

Results: Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment.

Conclusions: HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent.

Keywords: HCV; HIV; TURQUOISE; co-infection; darunavir; direct-acting antiviral; ART.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anilides / therapeutic use
  • Anti-Retroviral Agents / therapeutic use*
  • Body Mass Index
  • CD4 Lymphocyte Count
  • Carbamates / therapeutic use
  • Coinfection / drug therapy
  • Darunavir / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • HIV-1 / drug effects
  • HIV-1 / isolation & purification
  • Hepacivirus / drug effects
  • Hepacivirus / isolation & purification
  • Hepatitis C / drug therapy*
  • Humans
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Ribavirin / therapeutic use
  • Ritonavir / therapeutic use
  • Sulfonamides / therapeutic use
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Young Adult

Substances

  • ABT-267
  • ABT-333
  • Anilides
  • Anti-Retroviral Agents
  • Carbamates
  • Macrocyclic Compounds
  • Sulfonamides
  • Ribavirin
  • Uracil
  • Ritonavir
  • paritaprevir
  • Darunavir