Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice.
Real-world data are needed to inform hepatitis C virus (HCV) treatment decisions.



To assess the comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) vs. ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± RBV in genotype 1 HCV patients treated in routine medical practice.



Observational intent-to-treat cohort of genotype 1 patients initiating 8 or 12 weeks of LDV/SOF ± RBV or 12 weeks of OPrD ± RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10 weeks after end of treatment.



6961 patients initiated LDV/SOF (N = 4478), LDV/SOF + RBV (N = 1269), OPrD (N = 297), and OPrD + RBV (N = 917) at 126 facilities. Intention-to-treat SVR rates were 91.4% (3813/4170) for LDV/SOF, 90.0% (1098/1220) for LDV/SOF + RBV, 95.1% (269/283) for OPrD and 85.8% (746/869) for OPrD + RBV. SVR rates in those completing 8 weeks of LDV/SOF were 91.7% (1223/1333) and 12 weeks of LDV/SOF 94.6% (2475/2615), LDV/SOF + RBV 92.2% (1033/1120), OPrD 98.0% (248/253) and OPrD + RBV 95.5% (705/738). Significant predictors of SVR were African American race (OR 0.71, 95%CI 0.59-0.86, P < 0.001), body mass index (BMI) > 30 kg/m(2) (OR 0.73, 95% CI 0.60-0.89, P = 0.002), FIB4 > 3.25 (OR 0.60, 95% CI 0.49-0.72, P < 0.001), OPrD + RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48-0.76, P < 0.001) and subtype 1b (OR 1.38, 95% CI 1.11-1.71, P = 0.003). For those completing 12 weeks, FIB-4 > 3.25 and high BMI remained significant predictors.



In this robust real-world cohort, SVR rates were similar to clinical trials. FIB-4 > 3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD + RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12-week course.
Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
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LI
Backus
Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
P S
PS
Belperio
Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
T A
TA
Shahoumian
Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
T P
TP
Loomis
Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
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LA
Mole
D015081:2-Naphthylamine; D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D002219:Carbamates / Q000627:therapeutic use; D003521:Cyclopropanes; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D014633:Valine; D055815:Young Adult
D000813:Anilides; D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D005449:Fluorenes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D012367:RNA, Viral; D013449:Sulfonamides; C586541:ledipasvir; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir; D000069474:Sofosbuvir