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



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.



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.



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.
University of Colorado School of Medicine, Denver, USA.
David
D
Wyles
Center for AIDS Research, University of Alabama, Birmingham, USA.
Michael
M
Saag
AbbVie Inc, North Chicago, Illinois, USA.
Rolando M
RM
Viani
Quest Clinical Research, San Francisco, California, USA.
Jacob
J
Lalezari
Ruth M. Rothstein CORE Center, Chicago, Illinois, USA.
Oluwatoyin
O
Adeyemi
AIDS Healthcare Foundation, Beverly Hills, California, USA.
Laveeza
L
Bhatti
AbbVie Inc, North Chicago, Illinois, USA.
Amit
A
Khatri
AbbVie Inc, North Chicago, Illinois, USA.
Jennifer R
JR
King
AbbVie Inc, North Chicago, Illinois, USA.
Yiran B
YB
Hu
AbbVie Inc, North Chicago, Illinois, USA.
Roger
R
Trinh
AbbVie Inc, North Chicago, Illinois, USA.
Nancy S
NS
Shulman
Ruane Medical & Liver Health Institute, Los Angeles, California, USA.
Peter
P
Ruane
D015081:2-Naphthylamine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000813:Anilides / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy; D003521:Cyclopropanes; D000069454:Darunavir / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D016174:Hepacivirus / Q000187:drug effects / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012254:Ribavirin / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D014633:Valine; D055815:Young Adult
D000813:Anilides; D044966:Anti-Retroviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir; D000069454:Darunavir
HCV; HIV; TURQUOISE; co-infection; darunavir; direct-acting antiviral; ART