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Alcohol and AIDS : Biomedical Research

WHAT ARE THE MOST IMPORTANT QUESTIONS FACING ALCOHOL-AIDS RESEARCH?

I. Does alcohol consumption modulate susceptibility to primary HIV infection?

II. Does alcohol consumption accelerate progression of HIV disease or predispose to new complications of HIV infection?

III. What are the interactions and consequences of alcohol rinking and prevention measures?

Intense investigations into the biologic determinants of HIV disease have begun to yield interventions that can transform HIV disease from a fatal condition to a chronic, manageable disease syndrome. As understanding of the pandemic progresses, and as HIV/AIDS research becomes more focused, it is becoming increasing apparent that cofactors such as alcohol consumption may play an important role in sexual transmission, susceptibility, and progression of HIV disease.

  • At an inner city alcohol treatment center, approximately 3.5- 4.5% of those who use alcohol exclusively and 46% of alcohol abusers who had a history of injecting drug use were HIV+; women who were exclusively alcohol-dependent had a 20% rate of infection (Schleifer, et al.; Alcoholism Clin Exp Res 20:75-80, 1996).

  • Contact with primary care providers by HIV infected alcoholics occurs almost 24 months later than those without alcohol abuse problems after infection (28 months vs 4 months). This delay results in missed opportunities to receive timely preventive care, including HIV risk reduction interventions, addictions behavioral counseling, prevention of complications of HIV, and ongoing treatment of secondary infections (Samet; Abstract Soc Gen Int Med, 1995).

  • HIV-1 replication in vitro is significantly enhanced in peripheral blood mononuclear cells isolated from individuals infused with ethanol (Bagasra, et al.; J Infect Dis 173:550-558, 1996).

In 1995, the NIAAA convened an AIDS Strategic Planning Workshop to develop and prioritize a research agenda on AIDS-related biomedical research in accord with the mission of the Institute. The priority questions and strategic areas of research are presented here.

I. Strategies to study the effects of alcohol consumption on modulating host susceptibility to primary HIV infection should include investigations on:

  • HIV infectivity on host immune function
    Specific studies on immune activation, suppression, and differentiation, and alteration of cytokine production by lymphocytes, monocytes/macrophages, dendritic cells, and neural cells

  • HIV factors
    Specific studies on early replication events such a attachment, uncoating and reverse transcription

  • Host organ systems that may alter HIV infectivity and/or replication characteristics Specific studies on mucosal integrity, mucosal immunity, inflammation, microflora, and viral uptake

  • Other host factors that may alter HIV infectivity
    Specific studies on nutritional consequences, changes in regional immunity, and interactions with underlying disease, e.g. alcoholic liver disease and alcoholic neurologic disease, and other sexually transmitted diseases

II. Strategies to elucidate the effects of alcohol consumption on acceleration of progression of HIV disease or on predisposition to new complications of HIV infection should include studies on:

  • HIV-infected cells
    Studies on upregulation of HIV gene expression and replication in permissive cells, and in activated versus resting CD4+ cells; cytopathogenic effects; cell-to-cell transmission; and differences in HIV phenotype

  • Host immune mechanisms directed against HIV
    Studies on whether ethanol enhances the acquisition of Th2-like state by T cells of HIV+ patients or enhances the immunodeficient state in animal models of ethanol consumption and AIDS

  • Host immunosuppression as a consequence of HIV infection
    Studies on localized and systemic opportunistic infections; cancer development, progression, and metastasis

  • HIV-specific complications
    Studies on the pathogenic processes involved in HIV wasting, neuropathy, encephalopathy, and enteropathy

  • Reversibility of the above effects with diminished alcohol consumption or with abstinence

III. Strategies to study the interactions and consequences of alcohol drinking and prevention measures with HIV-disease and related therapies should include:

  • Interactions of ethanol and HIV-related treatment protocols, including nutritional therapies and immune modulators
    Studies that evaluate whether ethanol alters efficacy of AIDS treatment strategies, especially by interfering with drug absorption and altered hepatic drug metabolism; whether ethanol increases toxicity of AIDS therapeutics; and whether alcohol consumption alters compliance with AIDS medical protocols

  • Interactions of HIV disease and HIV-related therapies with the treatment of alcoholism
    Studies that assess whether HIV-related therapeutics alter efficacy of alcoholism treatment medications; whether HIV-related therapies increase toxicity of alcoholism treatment medications; and whether HIV disease (i.e., AIDS dementia, affective disorders) or HIV-related protocols alter compliance to alcoholism treatment strategies

OTHER RECOMMENDATIONS:

  • The study subjects for these investigations should include populations comprising the elderly, women, emergency room populations, individuals who are co-dependent with other drugs, and other persons who are at high risk for HIV infection.

Information on basic science research grants can be obtained from:

Diane L. Lucas, Ph.D.
Program Director
Biomedical Research Branch
National Institute on Alcohol Abuse and Alcoholism
Willco Building, Suite 402
6000 Executive Boulevard, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-8744; Fax: (301) 594-0673
E-Mail: dlucas@mail.nih.gov

Information on behavioral research grants can be obtained from:

Kendall Bryant, Ph.D.
AIDS Coordinator - Behavioral Research
Division of Clinical and Prevention Research
National Institute on Alcohol Abuse and Alcoholism
Willco Building, Suite 505
6000 Executive Boulevard, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-8820; Fax: (301) 443-8774
E-Mail: KBryant@Willco.NIAAA.NIH.GOV

Derived from the NIAAA Extramural Program Descriptions Handbook, 1995 and Program Announcement Alcohol Abuse, HIV, and Infectious Disease.

Updated: March 2003


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