|Home | About | Journals | Submit | Contact Us | Français|
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.
The MEG Workshop participants made a set of following recommendations for future research on MEG disorders in HIV-infected drug abusers.
Conduct epidemiologic studies concerning underlying metabolic and pathophysiologic consequences of MEG disorders.
Assess nutritional status (serum levels of macronutrients and micronutrients) in drug-abusing populations.
Study the effects of malabsorption on infections; immune status; and physical, cognitive, and neuroendocrine function.
Determine whether a link exists between HIV and malnutrition in drug abusers.
Study the role of individual micronutrients and body composition changes.
Study the role of nutrients and micronutrients in neurocognitive function.
Study the mechanism of action of micronutrients and antioxidants in MEG disorders.
Conduct multicenter and multidisciplinary studies of the effects of individual drugs of abuse on MEG disorders in various populations.
Differentiate between the effects of MEG disorders, drug abuse, and HIV infection.
Study immune dysfunction and associated metabolic deficits associated with HIV infection and drug abuse in special populations such as children and adolescents; pregnant women; and other underserved populations such as African Americans, Hispanics, and Native Americans.
Study interactions among drugs of abuse and antiretroviral and other therapeutic agents.
Develop nutritional therapies for substance abusers with malnutrition, lipodystrophy, pregnancy, or sarcopenia.
Determine nutritional consequences of drug rehabilitation.
Assess safety and efficacy of nutritional therapies for substance abusers. Determine relevant treatments to improve body composition, muscle strength, viral load, cytokine levels, metabolic changes, quality of life, and disease progression and survival.
Develop animal models to study the underlying mechanisms of action of micronutrients.
Develop or improve methods to assess MEG disorders in HIV-infected or uninfected drug abusers.
The panel recommended that NIH/NIDA establish a special grant review committee or include relevant expertise in an existing committee and provide sufficient funds to support research in this developing area.