Introduction to the Special Issue Clinical Pharmacology in Drug Development 2017, 6(2) 108–117 C  2017, The American College of Clinical Pharmacology DOI: 10.1002/cpdd.316 Drug–Drug Interactions and Diagnostics for Drug Users With HIV and HIV/HCV Coinfections: Introduction Jag H. Khalsa 1 , Andrew H. Talal 2 , and Gene Morse 2 Abstract Substance use and pharmacologic treatment of co-occurring infections such as human immunodefciency virus (HIV) and hepatitis C virus (HCV) are associated with many adverse consequences including pharmacokinetic and pharmaco- dynamic drug–drug interactions (DDIs). The National Institute on Drug Abuse sponsored a 2-day conference on DDIs at which clinicians/scientists from government, academia, and the pharmaceutical industry presented the most current research fndings to formulate a comprehensive overview of DDIs. Specifc topics discussed included drug metabolism; drug interactions between medications used in the treatment of HIV, HCV, and substance use disorders; intrahepatic concentrations and methods of assessment of drugs in liver disease of varying etiologies and degrees of impairment; and minimally invasive sampling techniques for the assessment of intrahepatic drug concentrations, viral replication, and changes in gene expression in response to treatment. Finally, the speakers identifed research targets and priorities on DDIs.Areas of emphasis included development of diagnostic assays for drug concentration assessment in different organs, an enhanced understanding of factors responsible for alterations in drug metabolism and excretion, and establishment of clinical trials and work groups to study DDIs.Our long-term objective is to broaden investigation in the feld of DDIs in substance users. Keywords drug–drug interactions, pharmacokinetics/pharmacodynamics, HIV, HIV/HCV, drug abuse In 2014, 27 million Americans (10.2% of the popula- tion 12 years and older) used at least 1 illicit drug in the past month (NHSDA, 2015), 1 whereas 66.9 million Americans used tobacco, and an estimated 135 mil- lion reported current use of alcohol. The effect of alco- hol on the liver is compounded by the several hundred million people globally currently living with chronic hepatitis infection. An estimated 240 million people are chronically infected with viral hepatitis B in the world, 2 an estimated 170 million people are living with viral hepatitis C infection (Centers for Disease Con- trol and Prevention [CDC]), 3 of whom 3.5 million are living in the United States (CDC), 4 and an estimated 33 million globally are living with HIV infection, of whom an estimated 1 million are living in the United States. The use of both legal (tobacco and alcohol) and illegal (cocaine, opiates, amphetamines, and oth- ers) drugs and co-occurring infections are associated with serious medical and health consequences affect- ing almost every physiological and biochemical system. Nearly 40% of people with AIDS and up to 60%–90% with hepatitis C virus (HCV) infection nationwide are injection drug users. 5 Although major advances in an- tiretroviral therapy (ART for HIV/AIDS) and antivi- ral treatment (ARV for HCV infection) have provided signifcant beneft for persons infected with HIV and HCV, respectively, drug users as a population continue to have limited access to and poor utilization of avail- able therapies. Absence of clinical services, clinician concerns regarding adherence to complex medical regi- mens, the development of viruses resistant to ART and ARV regimens, and potential pharmacokinetic interac- tions, as well as patient concerns regarding side effects, 1 National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA 2 State University of New York at Buffalo, Buffalo, NY, USA Submitted for publication 29 August 2016; accepted 29 September 2016. Corresponding Author: Jag H. Khalsa, MS, PhD, Chief, Medical Consequences Branch, Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, National Institutes of Health, DHHS, 6001 Executive Blvd., Room 4137, Bethesda, MD 20892 (e-mail: jkhalsa@nida.nih.gov; jk98p@nih.gov)