Proton Pump Inhibitor Usage Reduces Sustained Viral Response Rates for Veterans With HIV/HCV Coinfection on Ledipasvir/Sofosbuvir

A Real-world Study From a Multicentre VA Cohort

Tzu-Hao Lee; Austin Chan; William Bryan; Lawrence Park; Mohamed Hashem; Mary Townsend; Cynthia Moylan; Rachel Britt; Steve Choi; Susanna Naggie


J Viral Hepat. 2021;28(4):630-636. 

In This Article


This study was a retrospective database analysis of all veterans who received LDV/SOF ± ribavirin (RBV) from 10 October 2014 to 31 December 2015. Data were obtained from the VA Corporate Data Warehouse (CDW) through the Veterans Affairs Informatics and Computing Infrastructure (VINCI). This study was approved by the local (Durham) Veterans Affairs (VA) Institutional Review Board (IRB) with additional approval from the VA Office of Information Technology. All sensitive study information and Personally Identifiable Information (PII) or Protected Health Information (PHI) was maintained on the secure VINCI project server. Only aggregate data without PII/PHI were transferred out from VINCI.

Our cohort included all veterans who received LDV/SOF ± RBV during the study period. We excluded those with incomplete data for sustained virologic response at week 12 (SVR12) and those who received a course of LDV/SOF ±RBV therapy that was not considered the standard of care per the AASLD/IDSA HCV Treatment and Management Guidelines[16] during the relevant study period (Figure S1). The primary endpoint was SVR12, defined as an undetectable hepatitis C viral load by polymerase chain reaction (PCR) assessed at a minimum of 10 weeks following the completion of LDV/SOF ± RBV therapy. For the veterans with multiple viral loads after the end of therapy, the most recent one was used. Treatment end dates were defined by the pharmacy database record.

The primary exposure variable was the usage of acid suppression medications (PPI or H2B) during LDV/SOF ± RBV therapy. Veterans were considered to be on acid suppression medication if VA pharmacy records confirmed release of these medications at least one time immediately prior to the DAA therapy (between 90 days prior and the start of DAA therapy) and one time during the antiviral therapy (between the start day of the DAA therapy and 90 days afterwards). An active prescription extending at least 7 days into the course of DAA therapy was also required to exclude the patients whose PPI prescription was discontinued at the beginning of DAA therapy. High-dose PPI usage was defined as having received more than 7 days of any PPI dose equivalent that was higher than 20 mg omeprazole. The dosing frequency was identified as daily or twice daily by pharmacy dosing records.

Veterans who had a FIB-4 score greater than 3.25 were categorized as having cirrhosis, and veterans who had received any medication that was considered standard of care therapy for HCV prior to the prescription of LDV/SOF were categorized as treatment-experienced. This included interferon, ribavirin, boceprevir, telaprevir and simeprevir. Additional clinical characteristics obtained included age, sex, race, platelet count, HCV genotype, treatment duration of LDV/SOF, ribavirin and HIV status. HIV infection was defined as any veteran who had a positive HIV antibody.

Descriptive statistics are presented as medians and quartiles for continuous variables and counts and percentages for categorical measures. Multivariable logistic models were fit to estimate the association between usage of acid suppression medications and SVR and were adjusted for clinical factors (age, sex, race, platelet count, HIV status, cirrhosis, prior HCV treatment, treatment duration of LDV/SOF and ribavirin). These models were weighted with the inverse probability of acid suppression medication use to account for non-random selection to this treatment.