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NIAAA
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.
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