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

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.

• Authors: David Wyles, Michael Saag, Rolando M Viani, Jacob Lalezari, Oluwatoyin Adeyemi, Laveeza Bhatti, Amit Khatri, Jennifer R King, Yiran B Hu, Roger Trinh, Nancy S Shulman, Peter Ruane
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 215 Issue 4 Pg. 599-605 (02 15 2017) ISSN: 1537-6613 [Electronic] United States
• PMID: 28329334 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

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

Topics

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