The Challenge of Potential Drug-Drug Interactions Among People Living With HIV on Antiretroviral Therapy: A Cross-Sectional Study in Selected Provinces in China.

Huan Xia,Tong Zhang,Tong Zhang,Xiaojie Huang,Ping Ma,Ping Ma,Xiaowen Gong,Liying Gao,Hao Wu,Hao Wu,Silvere D Zaongo,Silvere D Zaongo,Silvere D Zaongo

doi:10.3389/fphar.2020.00800

Abstract

ObjectivesPotential drug–drug interactions (DDIs) are a significant therapeutic threat among human immunodeficiency virus (HIV)-positive individuals on antiretroviral (ARV) medications. DDIs involving ARV drugs in mainland China are unknown and insufficiently described. Herein, we investigated the prevalence and frequencies of potential ARV DDIs in Chinese people living with HIV (PLWH), then we assessed the risk factors associated with potential DDIs.MethodsThis study was conducted with HIV-positive adults undergoing ARV medications from multiple centers across China. The latest prescription of each participant was evaluated for potential DDIs using the Liverpool HIV drug interaction database. Multivariable logistic regressions were used to evaluate the factors associated with DDIs.ResultsAmong 600 PLWH recruited, at least one non-HIV co-medication was observed in 511 (85.2%) individuals. A total of 2566 DDIs were identified, of which 11 (0.43%) and 311 (12.89%) were of contraindicated (red-flags) and dosage/timing adjustment required (orange-flags), respectively. Multivariate regression analysis revealed a higher risk of clinically significant DDIs (red- and orange-flagged comedication) associated with: the use of boosted protease inhibitors (p < 0.0001), boosted integrase strand transfer inhibitors (p < 0.0001), and non-nucleoside reverse transcriptase inhibitors-based ARV regimen (p < 0.0001); or the use of antiinfectives for systemic use (p < 0.0001), cardiovascular system drugs (p < 0.0001), nervous system drugs (p < 0.0001), fungal infection (p = 0.0071), and Herpes simplex virus infection (p = 0.0231).ConclusionsPotential DDIs and inappropriate medications constitute a burden for people living with HIV in China. The knowledge of DDIs patterns and the scan for DDIs is crucial. Indeed, they can help to prevent drug-related adverse outcomes in such immunodeficient population.

Highlights

Approximately 37.9 million people are living with human immunodeficiency virus (HIV)(Cambou and Landovitz, 2020)
Multivariate regression analysis revealed a higher risk of clinically significant drug-drug interactions (DDIs) associated with: the use of boosted protease inhibitors (p < 0.0001), boosted integrase strand transfer inhibitors (p < 0.0001), and non-nucleoside reverse transcriptase inhibitors-based ARV regimen (p < 0.0001); or the use of antiinfectives for systemic use (p < 0.0001), cardiovascular system drugs (p < 0.0001), nervous system drugs (p < 0.0001), fungal infection (p = 0.0071), and Herpes simplex virus infection (p = 0.0231)
Potential DDIs and inappropriate medications constitute a burden for people living with HIV in China

Summary

Introduction

Approximately 37.9 million people are living with human immunodeficiency virus (HIV)(Cambou and Landovitz, 2020). Advances in treatment have yielded effective regimens, antiretroviral (ARV) agents are among the most therapeutically risky for drug-drug interactions (DDIs) presenting significant risks to people living with HIV (PLWH) and a challenge for clinicians to ensure appropriate and safe prescribing (Gong et al, 2019; Cambou and Landovitz, 2020). Concomitant medication use is more prevalent in PLWH than in the general population (GimenoGracia et al, 2015) This setting is further accentuated by aging (Smith and Flexner, 2017; Ranzani et al, 2018; Back and Marzolini, 2020) and additional comorbidities such as opportunistic infections, non-acquired immune deficiency syndrome (AIDS) related comorbidities (Althoff et al, 2019), including non-AIDS malignancies, cardiovascular events, renal and hepatic diseases, and neurocognitive disorders often resulting in polypharmacy (usually defined as the simultaneous use of ≥ 5 drugs) (Courlet et al, 2019; Freedman et al, 2019; Edelman et al, 2020). The most wellrecognized DDIs mechanism is that many ARVs, especially pharmacologic boosters ritonavir or cobicistat-boosted protease inhibitors (PIs)-based and non-nucleoside reverse transcriptase inhibitors (NNRTIs), frequently lead to significant drug interactions since they may affect the cytochrome P450 enzymes or drug transporters as inhibitors, inducers or substrate involved with the metabolism of many commonly used medications for general medical care (Foy et al, 2014; Seden et al, 2017)

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