Sander Genser

Co-occurring hepatitis C, substance use, and psychiatric illness: Treatment issues and developing integrated models of care

Hepatitis C virus (HCV) infection is transmitted by injection drug use and associated with psychiatric conditions. Patients with drug use or significant psychiatric illness have typically been excluded from HCV treatment trials noting the 1997 National Institutes of Health Consensus Statement on HCV that indicated active drug use and major depressive illness were contraindications to treatment of HCV infection. However, the 2002 NIH Consensus Statement recognized that these patients could be effectively treated for HCV infection and recommended that treatment be considered on a case-by-case basis. Treating HCV infection in these patients is challenging, with drug use relapse possibly leading to psychosocial instability, poor adherence, and HCV reinfection. Interferon therapy may exacerbate preexisting psychiatric symptoms. Co-occurring human immunodeficiency virus or hepatitis B virus provide additional challenges, and access to ancillary medical and psychiatric services may be limited. Patients with co-occurring HCV infection, substance use, and psychiatric illness can complete interferon treatment with careful monitoring and aggressive intervention. Clinicians must integrate early interventions for psychiatric conditions and drug use into their treatment algorithm. Few programs or treatment models are designed to manage co-occurring substance use, psychiatric illness, and HCV infection and therapy. The National Institute on Drug Abuse convened a panel of experts to address the current status and the long-range needs through a 2-day workshop, Co-occurring Hepatitis C, Substance Abuse, and Psychiatric Illness: Addressing the Issues and Developing Integrated Models of Care. This conference report summarizes current data, medical management issues, and strategies discussed.

Clinical consequences of marijuana.

As documented in national surveys, for the past several years, marijuana has been the most commonly abused drug in the United States, with approximately 6% of the population 12 years and older having used the drug in the month prior to interview. The use of marijuana is not without significant health hazards. Marijuana is associated with effects on almost every organ system in the body, ranging from the central nervous system to the cardiovascular, endocrine, respiratory/pulmonary, and immune systems. Research presented in this special supplement will show that in addition to marijuana abuse/dependence, marijuana use is associated in some studies with impairment of cognitive function in the young and old, fetal and developmental consequences, cardiovascular effects (heart rate and blood pressure changes), respiratory/pulmonary complications such as chronic cough and emphysema, impaired immune function leading to vulnerability to and increased infections, and the risk of developing head, neck, and/or lung cancer. In general, acute effects are better studied than those of chronic use, and more studies are needed that focus on disentangling effects of marijuana from those of other drugs and adverse environmental conditions.

Women living with drug abuse and HIV disease: drug abuse treatment access and secondary prevention issues.

In collaboration with the National Institute on Drug Abuse, the Health Resources and Services Administration is conducting a multisite, longitudinal study on issues of service needs, service utilization, and access to care for drug abusers with HIV. This article discusses access to drug abuse treatment and HIV secondary prevention for 116 women interviewed during the studys first year in five U.S. cities. Using interview data from 115 service providers in those same cities, it also discusses drug abuse treatment availability and barriers to service expansion for drug users with HIV. Study findings indicate that there are highly significant gaps between the drug abuse treatment services these women feel they need and those they have been able to receive; these were particularly pronounced for drug detoxification and residential and outpatient drug-free treatment. Women who used crack cocaine or injection drugs had particularly high levels of need for residential and outpatient drug abuse treatment, while women who use crack were found to have significantly less experience with the drug abuse treatment system than IDUs. HIV secondary prevention was also found to be a critical need for these women, many of whom were engaging in behaviors that place them at risk for reinfection, infection with other diseases, and transmission to others. Providers indicated that lack of funding was the major barrier to expanding services for this population; other barriers, such as lack of ancillary services and transportation, were also noted. Two positive findings were that many drug abuse treatment agencies in these cities provide a wide range of ancillary services and that many different kinds of agencies offer drug abuse treatment services.

Interventions for Metabolic and Endocrine Complications of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Illicit Drug Use

Illicit drug use and concurrent infection with human immunodeficiency virus (HIV) are associated with metabolic and endocrine complications that may include lipid, carbohydrate, and endocrine metabolism disorders and nutritional deficiencies. Interventions for these metabolic and endocrine complications range from micronutrient supplementation to hormone-replacement therapy. We present the current strategies for the management of metabolic and endocrine disorders of HIV/acquired immunodeficiency virus and drug use. In addition, the panel members (contributing authors of the present supplement) recommend further research to determine the nature and extent of problems and to design better and effective therapies.

Introduction: Metabolic, Endocrine, and Gastrointestinal (MEG) Disorders in Drug Abuse and HIV/AIDS

The 1997 National Household Survey on Drug Abuse found that an estimated 13.9 million Americans ≥12 years of age used at least one illicit drug daily. The use of illicit drugs (e.g., cocaine, opiates, amphetamines) is associated with serious medical and health consequences affecting every tissue or organ system. Consequences include, for example, neurotoxicity of cocaine and meth-amphetamine, cardiovascular complications of cocaine, impairment of the immune system, and metabolic and endocrine disorders of cocaine and other drugs. HIV infects CD4 lymphocytes and macrophages, causing profound immunosuppression that eventually may develop into full-blown AIDS. Since 1981, when AIDS was first identified, more than 1 million Americans have become infected with HIV. According to the U.S. Centers for Disease Control and Prevention (CDC), drug use remains the second most common mode of exposure among AIDS cases nationwide. Through June 1997, illicit drug injection–related AIDS cases represented 32% of total diagnoses in the U.S. In addition to drug abuse as a factor in initial exposure to HIV, ongoing drug abuse, correlates of the lifestyles associated with drug abuse, and issues of access and adherence to treatments for drug abuse and its associated medical consequences are some ways in which drug-related factors interact with the onset and course of HIV disease. Although virtually every organ system can be affected during the course of HIV infection, the subject of this supplement is the metabolic, endocrine, and gastrointestinal (MEG) disorders that have been observed frequently among AIDS patients, especially those with a history of or ongoing drug abuse. HIV/AIDS-associated MEG disorders may interact with drug abuse in many ways. Wasting syndrome is a frequent major medical complication causing higher morbidity and mortality in drug users with HIV/AIDS than in other HIV/AIDS subpopulations. This may be attributed to the direct or indirect effects of illicit drugs on mucosal, vascular, and normal cellular enzymatic functions. In fact, cocaine, because of its vasoconstrictive properties, may exacerbate the effects of HIV on the gastric mucosa. It may also affect the intestinal mucosal absorption of nutrients and antiretroviral drugs. Specific micronutrient deficiencies result in glutathione system dysfunction that is associated with cellular and organ damage. The lack of adequate nutrition, coupled with drug abuse during pregnancy, may lead to fetal and childhood developmental disorders such as impaired memory, cognition, and brain maturation. Although total parenteral nutritional (TPN) support has been somewhat successful in the treatment of early stages of AIDS, the role of trace elements (e.g., selenium, zinc), vitamins (particularly B6 and B12), and other factors such as growth hormone as chemoprotective agents in HIV-infected drug users remains to be established. With these facts in mind, the Center on AIDS and Other Medical Consequences of Drug Abuse (CAMCODA), National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH), and the Office of Dietary Supplements (ODS) convened a workshop on MEG disorders in drug users infected with HIV. NIDA supports more than 85% of the world’s research on the medical aspects of drug abuse and addiction. CAMCODA supports research on AIDS-related and other conditions in drug abusers and collaborates with other components of NIH, and the mission of ODS is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public to foster an enhanced quality of life and health for the U.S. population. On August 3 and 4, 1998, a group of expert clinicians and scientists in the fields of drug abuse, HIV/AIDS, nutrition, metabolism, and endocrinology presented recent research findings with potential relevance to MEG disorders in drug abusers with HIV/AIDS and recommended future research directions for NIH. On the subject of metabolic disorders in HIV infection, Graham (Virco Group, Durham, NC, U.S.A.) presented a review of metabolic disorders as peripheral lipodystrophy, hyperlipidemia, hypercholesterolemia, and insulin resistance that occur among AIDS patients treated with highly active antiretroviral therapeutics (HAART). Tang and Smit (Johns Hopkins) showed that HIV-positive intravenous drug users (IVDUs) receiving HAART had significantly higher mean serum levels of several antioxidants, independent of dietary and supplemental intake, compared with both HIV-negative and HIV-positive patients who were not receiving HAART, suggesting that oxidative stress may be reduced in patients receiving protease inhibitor therapy. Watson et al. (University of Arizona) presented the results of studies showed that the murine AIDS model offered a rapid, economic, and immunologically relevant means of assessing the effects of hormones and nutrient supplements on retroviral and drug-induced immune damage. Wahlstrom and Dobs (Johns Hopkins University) presented evidence that the hypogonadism observed in the presence of HIV infection is due to the general effects of the chronic illness and the specific effects of associated drugs and infections. They hypothesized the possible benefits of hormonal replacement therapy on body composition. Arpadi (Columbia University) discussed the role of dietary intake and associated HIV replication and reported that, despite relative decreases in total energy expenditure, a significant energy deficit was observed in children with HIV-associated growth failure. Gorbach et al. of Tufts University observed that HIV-positive women, but not men, who inject drugs intravenously may be at high risk of AIDS-related wasting syndrome. They further suggested that additional research was needed to develop appropriate nutritional interventions for HIV-infected, drug-using women and members of minority communities. Baum (University of Miami) reported that deficiency of dietary selenium was associated with a 20-fold increase in mortality among HIV-infected IVDUs and that selenium status could be a sensitive predictor of wasting in HIV-1–infected individuals. Taylor et al. (University of Georgia) presented evidence that HIV encodes viral selenoproteins genes, the expression of which could cause a decline in cellular selenoproteins levels. This suggests a novel mechanism by which selenium deficiency may exacerbate the effects of HIV infection, particularly in drug abusing populations subject to the dual risk factors of malnutrition and increased oxidative distress. After reviewing the strengths and weaknesses of biochemical measurements (e.g., blood nutrients, lipids, and albumin), body composition (e.g., height, weight, bioimpedance, and dual-energy x-ray absorptiometry [DEXA]), and dietary intake (e.g., 24-hour recalls, food records, food frequencies) as parameters employed in the assessment of nutritional status, Smit and Tang (Johns Hopkins) recommended the development of diagnostic tools that can be used to measure changes in the nutritional status of HIV-infected IVDUs over time. With respect to medical consequences of drug abuse and HIV infection, although Shor-Posner (University of Miami) suggested that cognitive impairment among HIV-infected IVDUs was related to deficiencies in selenium and vitamin B12, Hickey (University of California at San Francisco) (did not submit paper for publication in this supplement) emphasized that skin abscesses and other dermatologic complications were more serious consequences that previously have not been reported among HIV-infected IVDUs. Abrams (University of California at San Francisco) presented a multipronged alternative to therapy based on nutritional and/or single pharmacologic interventions that have been found to be generally unsatisfactory in the treatment of AIDS-associated wasting. He discussed strengths and weaknesses of dietary supplements and the appetite stimulants (e.g., megestrol acetate and dronabinol) for the treatment of HIV-associated anorexia and weight loss; smoking marijuana; anabolic agents (e.g., testosterone), recombinant human growth hormone alone or in combination with appetite stimulants or resistance exercise; and inhibitors of tumor necrosis factor-α (e.g., thalidomide), that are being investigated and show some promise as therapy, with combination regimens currently under evaluation. Finally, Kotler (Columbia University) stated that the complex nature of AIDS-related wasting necessitates individualized strategies and that efficient and cost-effective treatment measures should be designed for HIV/AIDS patients. The participants concluded that additional research was needed in the area of metabolic and endocrine disorders, elucidating the underlying mechanisms of action of micronutrients, development of assessment tools to measure malnutrition and wasting, and design of intervention modalities applicable to HIV-infected drug abusers.