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

Abstract and Introduction


Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex drug interactions. This retrospective study evaluates the effects of acid suppression medications (PPI or H2-receptor antagonist [H2B]) use and SVR rates in patients with HIV/HCV or HCV and taking LDV/SOF in a large multicentre veteran cohort. Patients in the Veterans Affairs Health Care System who received LDV/SOF ± ribavirin from 10/10/2014 to 12/31/2015 were included. The odds ratios (OR) of PPI or H2B use for SVR were adjusted for clinical factors and with inverse probability of treatment weighting for non-random treatment selection for acid suppression medication use. There were 9703 veterans included in our final analysis. After adjustment of other clinical factors, PPI use is associated with a lower SVR in the overall cohort (95.0% vs. 96.1%, OR: 0.86, 95% CI: 0.74–0.99, p = .03, number needed to harm 90.9) and HIV/HCV coinfection subgroup (93.4% vs. 96.9%, OR: 0.47, 95% CI: 0.26–0.85, p = .01, number needed to harm 28.6). This present study reveals PPI use is associated with reduced SVR after LDV/SOF treatment, with a more significant impact in the subgroup of patients with HIV/HCV coinfection. Precautions need to be taken when using PPI and LDV/SOF in this group of patients.


Due to overlapping modes of transmission, it is estimated that 2.3 million people live with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection worldwide.[1] Although historically, responses to interferon-based HCV treatment were lower for people with HIV, this changed with the approval of direct-acting antiviral (DAA) therapies.[2–4] The sustained viral response (SVR) with DAA therapy is high for people with HCV infection, regardless of concomitant HIV infection.[5–7] Thus, the approach to HCV treatment is the same for people with HCV and HIV/HCV coinfection. While response rates and treatment approaches are the same for people with HIV/HCV coinfection, there remains a need for attention to the drug-drug interactions that arise from concomitant dosing of antiretrovirals (ARVs) and DAA. Due to ARV-DAA drug interactions, there is the added risk of more complex pharmacology when additional medications with known DAA drug interactions are also prescribed.

Ledipasvir/sofosbuvir (LDV/SOF) is one of four recommended combination DAA regimen for initial treatment of chronic HCV infection. One of the more commonly encountered drug-drug interactions for LDV/SOF is the decreased solubility of ledipasvir with an increase in gastric pH, which occurs with acid suppression medications, including proton pump inhibitors (PPI) and H2-receptor antagonist (H2B).[8] According to the package insert, concomitant dosing of LDV/SOF with acid suppression medications can decrease the concentration of LDV, an effect that varies by the potency of each drug. While H2B and low-dose PPIs (omeprazole 20 mg daily or equivalent) can be administered under strict dosing schedules with LDV/SOF, a PPI dose equivalent higher than 20 mg daily while taking LDV/SOF is not recommended. Previous studies have reported an association of PPI use with reduced SVR in patients taking LDV/SOF[9,10]

For patients with HIV/HCV coinfection, the relationship between PPI use and SVR has not been extensively studied. A study focused on DAA effectiveness in veterans with HIV/HCV included 895 veterans who received 12 weeks of LDV/SOF with or without ribavirin, of which 146 had a prescription for PPI.[11] There was no significant difference in SVR for those on PPI (89.7%) and those not on PPI (91.5%). However, there was no assessment of the dose of PPI, and as this was not a primary hypothesis in the study, it is not clear how reliable the data was for daily PPI use. Previous pharmacokinetic studies showed that patients with HIV/HCV coinfection have lower concentrations of LDV compared to patients with HCV mono-infection, potentially the result of more complex drug interactions[12] or due to elevated gastric PH reported in people with HIV.[13–15] We hypothesize that adding a PPI to the ARV-DAA drug interaction may further impact the ledipasvir drug exposure and, ultimately, the SVR rate. Due to the unique challenges related to drug-drug interactions in people with HIV, it is important to identify any factors that may impact SVR.

In this study, we evaluated the effects of acid suppression medication (PPI and H2B) use on SVR rate in veterans with HCV or HIV/HCV infections treated with LDV/SOF in a large multicentre veteran cohort.