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

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          Abstract

          Objectives

          Potential 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.

          Methods

          This 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.

          Results

          Among 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).

          Conclusions

          Potential 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.

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          Most cited references27

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          Optimizing Treatment for Adults with HIV/AIDS in China: Successes over Two Decades and Remaining Challenges

          Purpose of Review The introduction of the National Free Antiretroviral Therapy Program (NFATP) in 2003 by the China National Center for AIDS/STD Control and Prevention has led to dramatic increases in antiretroviral therapy (ART) coverage among HIV-infected Chinese patients. Despite limitations in the number of available free antiretroviral drugs, the overall mortality associated with HIV/AIDS has dropped from 39.3 per 100 person-years in 2002 to 3.1 in 2014. In this review, we summarize the challenges, responses, and achievements of antiretroviral therapy (ART) in China over the past 20 years. Recent Findings Continuous optimization of the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment has been guided by data from serial domestic multi-center studies aimed at evaluating efficacy and toxicity of available ART regimens among Chinese patients with HIV, with the goal of maximizing adherence, access, and efficacy. In addition, increasing attention has been focused on the importance of continuity in the HIV care cascade to promote linkage to care, and address the multidisciplinary chronic care needs HIV/AIDS patients on lifelong ART. Summary Great progress has been achieved in the past 20 years in terms of access to and optimization of antiretroviral treatment in China. As the number of patients receiving long-term ART continues to grow, the focus of HIV/AIDS treatment has gradually transitioned from urgent care to the management of non-AIDS-related chronic complications and control of chronic inflammation.
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            The challenge of HIV treatment in an era of polypharmacy

            Abstract Introduction The availability of potent antiretroviral therapy has transformed HIV infection into a chronic disease such that people living with HIV (PLWH) have a near normal life expectancy. However, there are continuing challenges in managing HIV infection, particularly in older patients, who often experience age‐related comorbidities resulting in complex polypharmacy and an increased risk for drug‐drug interactions. Furthermore, age‐related physiological changes may affect the pharmacokinetics and pharmacodynamics of both antiretrovirals and comedications thereby predisposing elderly to adverse drug reactions. This review provides an overview of the therapeutic challenges when treating elderly PLWH (i.e. >65 years). Particular emphasis is placed on drug‐drug interactions and other common prescribing issues (i.e. inappropriate drug use, prescribing cascade, drug‐disease interaction) encountered in elderly PLWH. Discussion Prescribing issues are common in elderly PLWH due to the presence of age‐related comorbidities, organ dysfunction and physiological changes leading to a higher risk for drug‐drug interactions, drugs dosage errors and inappropriate drug use. Conclusions The high prevalence of prescribing issues in elderly PLWH highlights the need for ongoing education on prescribing principles and the optimal management of individual patients. The knowledge of adverse health outcomes associated with polypharmacy and inappropriate prescribing should ensure that there are interventions to prevent harm including medication reconciliation, medication review and medication prioritization according to the risks/benefits for each patient.
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              [Chinese guidelines for diagnosis and treatment of HIV/AIDS (2018)].

              (2018)
              (AIDS) is an important public health problem in China. In 2005, the first edition of the guidelines for the diagnosis and treatment of AIDS was formulated by the AIDS Professional Group of Society of Infectious Diseases of Chinese Medical Association, which was updated twice in 2011 and 2015. The fourth edition of the guidelines in 2018 is revised on the basis of national clinical practice and the latest research studies. The new research progress in opportunistic infections and human immunodeficency virus(HIV) associated cancers, antiretroviral therapy, HIV post-exposure prophylaxis, and prevention of mother to child transmission were updated in these guidelines. In the 2018 edition, pre-exposure prophylaxis is mentioned for the first time. The strategy of whole course management of HIV infection is put forward in the current version, which needs the participation of multidisciplinary team in prophylaxis, early diagnosis, individualized treatment and humanistic care.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                27 May 2020
                2020
                : 11
                : 800
                Affiliations
                [1] 1Department of Infectious Diseases, Nankai University Second People's Hospital , Tianjin, China
                [2] 2Department of Biostatistics, Tianjin Medical University , Tianjin, China
                [3] 3International School of Medicine, Tianjin Medical University , Tianjin, China
                [4] 4Department of Infectious Diseases, Beijing Youan Hospital, Capital Medical University , Beijing, China
                Author notes

                Edited by: Brian Godman, Karolinska Institutet (KI), Sweden

                Reviewed by: Johannes P. Mouton, University of Cape Town, South Africa; Yohana James Mashalla, University of Botswana, Botswana

                *Correspondence: Ping Ma, mapingtianjin@ 123456163.com ; Xiaojie Huang, huangxiaojie78@ 123456126.com

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work

                Article
                10.3389/fphar.2020.00800
                7266979
                55ccebd6-6268-4da6-a82f-ab96e32d586b
                Copyright © 2020 Xia, Gao, Gong, Zaongo, Zhang, Wu, Ma and Huang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 February 2020
                : 15 May 2020
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 33, Pages: 9, Words: 4958
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                drug–drug interactions,human immunodeficiency virus,antiretroviral drugs,ddi,hiv,china

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