Prevalence of Drug–Drug Interactions upon Addition of Simeprevir- or Sofosbuvir-Containing Treatment to Medication Profiles of Patients with HIV and Hepatitis C Coinfection

Abstract

The objectives were to (1) compare the frequency of contraindicated drug-drug interactions (XDDI) when simeprevir (SIM)- and sofosbuvir (SOF)-containing regimens are theoretically added to a patient's medication profile; (2) identify which hepatitis C (HCV) regimen is associated with the lowest frequency of XDDIs within different types of antiretroviral treatment (ART) regimens; and (3) determine the risk factors for XDDIs with each regimen. A cross-sectional study was performed among adult HIV/HCV-coinfected patients. Demographics, comorbidities, and medication lists were collected from medical records. Medication lists were entered into Lexi-Interact drug interaction software and XDDI before/after the addition of SIM- and SOF-containing therapy was documented. Classification and regression tree (CART) analyses identified breakpoints in continuous variables. Before the addition of any HCV therapy, XDDIs were present in 20% of the 335 included patients. After the addition of SIM-containing therapy, the frequency of XDDIs significantly increased to 88.4% (p<0.001). After adding SOF-containing therapy, the prevalence of XDDIs increased to 24.5% (p<0.001). The prevalence of XDDIs was significantly lower for SOF-containing HCV therapy within various types of ART regimens. Use of ≥7 non-HIV medications (CART breakpoint) was the only variable to predict XDDIs before the addition of any HCV therapy. Similarly, this was the only variable to predict XDDIs after the addition of SOF-containing therapy (PR: 4.80; 95% CI: 2.57-8.96, p<0.001). Variables independently associated with XDDIs after the addition of SIM-containing therapy were NNRTI regimen (prevalence ratio, PR: 1.62; 95% confidence interval, CI: 1.38-1.91, p<0.001), PI regimen (PR: 1.64; 95% CI: 1.40-1.93, p<0.001), and ≥7 non-HIV medications (PR: 1.06; 95% CI: 1.00-1.14, p=0.09). The addition of SOF-containing therapy was associated with a lower prevalence of XDDI than SIM-containing therapy.

High frequency of potential interactions between direct‐acting antivirals and concomitant therapy in HIV/hepatitis C virus‐coinfected patients in clinical practice

“…Previous studies on DDIs between DAAs and comedications among HIV/HCV‐coinfected patients focused on ART . In a large study on HIV/HCV coinfection in France, potential DDIs between DAAs currently available in that country and individual antiretroviral drugs were evaluated .…”

“…, SOF/LDV, among the currently recommended DAAs, showed the highest frequency of minor DDIs, involving two‐thirds of the patients. The rates of DDIs observed in other studies analysing DDIs between DAAs and ART in HIV/HCV coinfection show similar differences with those reported in the present study . The main reason for the higher rates of DDIs identified in the present study compared with previous studies is likely to be the inclusion of both ART and comedications.…”

“…DDIs between regimens currently recommended to treat HCV infection and ART or commonly prescribed medications are very frequent among HIV/HCV-coinfected patients. Previous studies on DDIs between DAAs and comedications among HIV/HCV-coinfected patients focused on ART [16][17][18]. In a large study on HIV/HCV coinfection in France, potential DDIs between DAAs currently available in that country and individual antiretroviral drugs were evaluated [16].…”

Nurse case management to improve the hepatitis C care continuum in HIV co‐infection: Results of a randomized controlled trial

“…Other barriers to engaging in HCV care include comorbidities and competing priorities such as substance use, poor access to specialty care, navigating the healthcare system, low knowledge and perceived threat of HCV, lack of provider expertise and nonreferral to specialty care by primary care providers . High prevalence of drug interactions between antiretroviral therapy (ART) and DAAs which may necessitate modification of ART regimens has introduced an additional barrier to initiating HCV treatment among PLWH …”

Management of drug interactions with direct‐acting antivirals in Dutch HIV/hepatitis C virus‐coinfected patients: adequate but not perfect

“…For instance, it was previously predicted that 51% of HIV/HCV-coinfected patients would have a cART regimen that would be contra-indicated with sofosbuvir/simeprevir or grazoprevir/elbasvir [5]. Co-medication other than cART can also be involved in DDIs [6]. This has already been shown for HCV-monoinfected patients [4,[7][8][9][10].…”