Thomas F. Kresina

Molecular medicine and hemochromatosis: At the crossroads

Abstract Summary of a conference sponsored by the Division of Digestive Diseases and Nutrition and the Division of Kidney, Urology and Hematology of the National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland GASTROENTEROLOGY 1999;116:193-207

Medication-assisted treatment and HIV/AIDS: aspects in treating HIV-infected drug users.

Drug use and HIV/AIDS remain serious public health issues in the US. The intersection of the twin epidemics of HIV and drug/alcohol use, results in difficult medical management issues for the healthcare providers who work in the HIV prevention and treatment fields. Access to care and treatment, medication adherence to multiple therapeutic regimens and concomitant drug–drug interactions of prescribed treatments are difficult barriers for drug users to overcome without directed interventions. Injection drug users are frequently disenfranchised from medical care and suffer stigma and discrimination creating additional barriers to care and treatment for their substance use disorders as well as HIV infection. Controlling the transmission of HIV will require access to care and treatment of individuals who abuse illicit drugs and alcohol. Improving health outcomes (e.g. access to and adherence to antiretroviral therapy) among HIV-infected substance users will also require access to evidenced-based pharmacological therapies for the treatment of drug abuse and dependence. The current review presents an overview of issues regarding the use of medication-assisted treatments for substance abuse and dependence among HIV-infected individuals, providing medical management paradigms for their care and treatment.

FK506 Enhances fibrogenesis in in vitro and in vivo models of liver fibrosis in rats

BACKGROUND/AIMSnThe immunosuppressant FK506 is undergoing clinical trials in transplantation and autoimmune diseases. FK506 modulates several cytokines and exerts hepatoprotection in acute models. This study was initiated to determine whether FK506 would be beneficial as an antifibrogenic agent.nnnMETHODSnFibrosis was induced by carbon tetrachloride administration to rats. Half of those animals were treated with FK506. The rats were killed after 8 weeks of carbon tetrachloride treatment. The livers were evaluated by histology, Northern hybridizations, and collagen quantitation. Additionally, rat fibroblasts were incubated with and without FK506 and used for Northern hybridization analysis.nnnRESULTSnSurprisingly, FK506 exacerbated hepatic inflammation and fibrosis. Increased hepatic collagen and higher messenger RNA levels of transforming growth factor beta 1 and collagens I, III, and IV were found in the FK506-treated group. Rat fibroblasts treated with FK506 expressed higher levels of collagens I and III, fibronectin, macrophage-colony stimulating factor, tissue inhibitor of metalloprotease, and transforming growth factor beta 1 messenger RNAs.nnnCONCLUSIONSnThese findings suggest that FK506 increases the expression of extracellular matrix genes and enhances fibrosis in the rat model. While further studies are needed to elucidate these profibrogenic mechanisms, caution is indicated for the unrestricted use of FK506 in patients subject to recurrent fibrogenic stimulation.

Integration of pharmacotherapy for opioid addiction into HIV primary care for HIV/hepatitis C virus-co-infected patients.

Pharmacotherapy for substance abuse is a rapidly evolving field comprising both old and new effective treatments for substance use. Opiate agonist therapy has been shown to diminish and often eliminate opiate use. This behavior change has resulted in the reduced transmission of many infections, including HIV, hepatitis C virus (HCV), and an enhanced quality of life. For the past 35 years, the provision of opioid agonist therapy has been limited to opioid treatment programmes. Opioid treatment programmes treat approximately 200 000 of the estimated million opiate-addicted individuals in the United States. With the need to increase the number of treatment opportunities available for opioid-dependent patients, Congress passed the Drug Addiction Treatment Act of 2000, which allows for the treatment of opioid dependence using buprenorphine by a properly licensed physician, including HIV primary care physicians. The integration of buprenorphine treatment for opioid addiction into HIV primary care thus provides a new treatment paradigm to address substance abuse in patients with HIV and HCV infections.

Human Immunodeficiency Virus Type 1 Infection, Mucosal Immunity, and Pathogenesis and Extramural Research Programs at the National Institutes of Health

Immune System of the Mucosa The immune system of mucosal surfaces functions to protect epithelial surfaces and underlying tissues and organs from environmental insult. It is an organism’s first line of defense against an array of pathogens that invade the host through mucosal surfaces by the generation of innate (nonimmune) mechanisms or the generation of mucosal immunity (or both). The mucosal immune system is the largest of all epithelial surfaces of the body, with the intestinal epithelium being the largest component of the mucosa. The mucosal immune system structurally comprises the salivary glands, Peyer’s patches, appendix, tonsils, mesenteric lymph nodes, and mucosal tissues of the respiratory, urinary, genital, and gastrointestinal tracts. The mucosal immune systems contain specialized cells relevant to human immunodeficiency virus (HIV) infection. M cells are epithelial cells found in organized lymphoid follicles that comprise, in part, the follicle-associated epithelium. The papers in this supplement discuss the interactions of HIV with M cells and other cells of the mucosa (i.e., epithelial cells, intraepithelial lymphocytes, most of which are of the CD8 phenotype and carry the a/b T cell receptor, and dendritic/macrophage cells) in infection and as part of the pathogenesis of HIV infection. In addition, important aspects of the mucosal immune system are presented, such as antigen processing and presentation, lymphocyte trafficking to and from the peripheral blood, the generation of oral tolerance, and the generation of humoral and cell-mediated immune responses germane to HIV infection, latency, disease progression, morbidity, and mortality.

Substance Abuse Treatment Utilizing Medication Assisted Treatment as HIV Prevention

International guidelines have been developed for the use of medications in the treatment of substance use disorders (WHO, 2008; WHO, 2009). Medications used in the detoxification from drug abuse and dependence provide symptomatic relief of drug and alcohol withdrawal. For long term treatment or medical maintenance treatment, medications eliminate the physiological effects of drug use by blocking drug-receptor binding in the brain and are an important part of the recovery process. The use of medication assistant treatment (MAT) is part of a comprehensive treatment plan for drug and alcohol dependence that addresses the medical, social, and psychological needs of the patient (SAMHSA, 2005; SAMHSA, 2009). An effective long term treatment paradigm for the successful treatment of alcohol or opioid dependence is the concomitant use of medications that block the effects of drug use in concert with behavior change counseling and psychotherapy. Medications which have demonstrated effectiveness in the long term treatment of opioid dependence are methadone, buprenorphine (subutex®, suboxone®), and naltrexone (Revia®, Depade®) or extended release injectable naltrexone (vivitrol®). Pharmacotherapies used in the treatment of alcohol dependence include acamprosate (Campral®), disulfiram (antabuse®, antabus®) and naltrexone (Revia®, Depade®) or extended release injectable naltrexone (vivitrol®). Time in treatment is a reliable indicator for successful treatment of drug dependence. Patients remain in treatment for longer periods of time when they perceive that their health care environment is supportive and non-stigmatizing, have a good patient-provider relationship, and feel that their needs are identified and met. Access to community-based substance abuse treatment that includes MAT is fundamental to achieving broad service coverage. Given that substance abuse treatment is Human Immunodeficiency Virus (HIV) prevention and the frequent co-morbidity of substance abuse and HIV infection, the provision of prevention, care and treatment for both need to be addressed in a coordinated manner for ideal patient outcomes. There are several models to achieve excellent patient outcomes for both HIV infection and the treatment of substance abuse (Proeschold-Bell et al 2010; Weiss et al, 2011). The highest level of coordinated care model has MAT and HIV services fully integrated with both the same medical record and health providers for both