Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

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Monday, February 26, 2007

Requests for Applications

1. Research Objectives

Purpose

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) invites a competing renewal of a cooperative agreement application to evaluate the cumulative and progressive effects on the brain of combined HIV infection and alcohol abuse in vivo using advanced magnetic resonance imaging techniques.

The investigator will work collaboratively under the cooperative agreement with NIAAA over a five -year period to conduct investigations of the separate and interactive effects of chronic alcohol use and HIV infection on neurocognitive function and brain structural and functional integrity.

The long-term goal is to understand the mechanisms of the brain structural and cognitive decline in heavy drinking HIV-infected individuals in order to develop better treatments for these cognitive and neurological deficits.

Background, Nature, and Scope of the Research Problem

Despite the advent of highly active antiretroviral therapy (HARRT) in the mid 1990's, and a reduction in AIDS-related opportunistic infections, there has been a recent resurgence in the frequency of HIV encephalitis and cognitive impairment in patients on stable antiretroviral therapy.

Research suggests that the re-emergence and progression of brain damage and cognitive impairments in HIV patients on long-term antiretroviral therapy may be due to the additive or interactive effects of multiple factors including development of drug resistance, Hepatitis C, nutritional factors, alcohol and/or drug abuse, chronic antiretroviral treatment, and aging.

Since hazardous or chronic alcohol use is a common problem in HIV infected individuals, it is important to study the additive and/or interactive effects of both conditions on brain structure and function.

In vivo neuroimaging data shows that HIV infection and chronic alcohol abuse affect many brain regions; particularly the frontal lobes, corpus callosum, basal ganglia, brainstem, and cerebellum.

Despite these overlapping areas of damage, only a few studies have used imaging technologies to examine the additive or interactive effects of these two diseases on brain structure and function.

Neuropsychological studies on the combined effects of HIV infection and chronic alcohol abuse, though limited, are also beginning to more consistently show additive and/or interactive effects of HIV and alcohol on cognitive performance. H

owever, the relationship between alcohol-related adherence problems and progression of cognitive decline is unknown.

Given the large investment and longitudinal nature of the investigation, it is necessary to have close Institute oversight and continually provide advice while not assuming the role of directing the research.

Objectives of this Research Program

This program is a five year continuation project using advanced magnetic resonance (MR) imaging technology (brain MR spectroscopy imaging and MR diffusion tensor imaging) to examine in vivo the macrostructural, microstructural and biochemical bases of the pathophysiology of HIV and alcohol abuse in dually afflicted individuals.

These techniques allow the observation of changes over time and the degree to which these disease-induced changes relate to clinical state and cognitive and motor performance.

Over the past five years, this project has evaluated the cumulative and progressive deleterious effects on the brain of combined alcohol abuse and HIV infection in an ethnically diverse community sample comprising four groups: high and low alcohol consuming HIV-infected subjects and high and low alcohol consuming HIV sero-negative subjects.

One-year follow-up on 82% of the entry sample, and three year follow-up on 75% have been completed. Cross-sectional analysis at study entry demonstrated substantial macrostructural, microstructural, and biochemical brain deficits in alcohol abusing patients with HIV infection, especially those whose disease had progressed to AIDS, compared with relative normality in asymptomatic HIV-infected patients. These findings are echoed in cognitive and motor performance and self-assessed quality of life.

Longitudinal analyses of structural MR indicate a prominent role for continued alcohol abuse in progressive brain damage among HIV-infected subjects, highlighting the need for detection and treatment of alcohol abuse in these patients.

In addition to the synergistic burden of alcohol abuse, the data also indicate significant effects of gender and self-identified ethnicity as important factors in detecting brain pathology.

The objectives of the next five years of this program are to

1) establish the pattern of brain pathology with MR imaging and functional measures in an expanded sample of individuals with HIV infection and the combined morbidity of alcohol abuse;

2) assess longitudinal HIV disease trajectory (progression or effective control) as modulated by alcohol abuse by continuing follow-up of the current cohort, testing them at 5 and 7 years after study entry; and

3) establish cross-sectional and longitudinal within-subject relationships among neuroimaging measures, cognitive and motor performance, and clinical status.

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