The National Advisory Council on Alcohol Abuse and Alcoholism (NIAAA) convened for its 133rd meeting at 5:30 p.m. on June 12, 2013, at the Fishers Lane Conference Center in Rockville, Maryland. The Council met in closed session for a review of grant applications and Merit Award extensions. The meeting recessed at 6:20 p.m. Dr. Abraham Bautista, Director, Office of Extramural Activities, presided over the closed session, which, in accordance with the provisions of Sections 552b(C)(6), Title 5, U.S.C. and 10(d) of Public Law 92-463, excluded the public for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds. Dr. Kenneth Warren, Acting Director, NIAAA, reconvened the Council in open session on June 13, 2013, at 9:00 a.m.

 

Council Members Present:

Andrea Barthwell, M.D.
Carol A. Casey, Ph.D.
Linda L. Chezem, J.D.
Fulton T. Crews, Ph.D.
Suzanne M. de la Monte, M.P.H., M.D.
Marianne L. Fleury
Joseph Thomas Flies-Away, J.D., M.P.A.
Andres G. Gil, Ph.D.
Kathleen Grant, Ph.D.
Paul J. Gruenewald, Ph.D.
Sarah N. Mattson-Weller, Ph.D.
Craig J. McClain, M.D.
Robert O. Messing, M.D.
Patricia E. Molina, M.D., Ph.D.
Gyongyi Szabo, M.D., Ph.D.

Ad Hoc Member Present: John Krystal, M.D., Yale University (by telephone)

Ex-officio Member Present: Daniel Kivlahan, Ph.D., Department of Veterans Affairs (by telephone)

Chairperson: Kenneth R. Warren, Ph.D.

Executive Secretary: Abraham P. Bautista, Ph.D.

Senior Staff: Vivian B. Faden, Ph.D.; Ralph Hingson, Sc.D., M.P.H., Robert Huebner, Ph.D.; Mr. Keith Lamirande; Howard Moss, M.D.; Gary Murray, Ph.D.; Antonio Noronha, Ph.D.

Other Attendees at the Open Sessions: Approximately 75 observers attended the open session, including representatives from constituency groups, liaison organizations, NIAAA staff, and members of the general public.

 

Call to Order and Introductions

Dr. Kenneth Warren called the open session of the 133rd meeting of the Council to order at 9:00 a.m. on Thursday, June 13, 2013. He welcomed participants to the meeting, and Council members and NIAAA senior staff introduced themselves. Dr. Warren introduced new Council members Judge Joseph Thomas Flies-Away and Dr. Robert Messing.
 

Director’s Report

Dr. Warren highlighted key recent Institute activities, referring to the written Director’s Report.

  • Director search. Upon the announcement that NIAAA would not merge with the National Institute on Drug Abuse (NIDA), the search began for a permanent NIAAA director. Council member Dr. Patricia Molina serves on the search committee.
  • NIAAA budget. NIAAA’s budget has been relatively flat since the early 2000s, and the Institute has lost considerable purchasing power since then. In FY2013 NIAAA received a budget allocation of $433.0 million, a $26.1 million (5.7%) drop from the FY2012 enacted level. Sequestration has forced the National Institutes of Health (NIH) to implement fiscal constraints across the board that affect staff, programs, intramural staff, and grantees. Funds overall declined by 6.3% from the FY2013 continuing resolution level. Consequently, Type 5 grants in all mechanisms will be awarded at 93% of the FY2013 commitment level. Funding for new competing grants is being reduced by a minimum of 10%. The number of new competing grants will decrease from 167 in FY2012 to 149 in FY2013. Sequestration will result in a drop in NIAAA’s success rate from 19% in FY2012 to approximately 15.5% in FY2013.  One positive perspective is that NIAAA’s success rate exceeds NIH overall’s rate for both FY2012 and 2013.

    The President has requested a 1.0% budget increase for NIAAA in FY2014 over the comparable base for FY2012, a 5.7% decline from the enacted FY2012 base. Optimism is not high that NIAAA would realize this increase based on the tenor of current budget discussions.

  • Functional integration. The Functional integration of addiction related research programs at NIH has been renamed Collaborative Research on Addiction at NIH (CRAN). It will foster co-morbid addiction-related activities across NIH. Participating (in proportion to their contribution to CRAN) are NIDA, NIAAA, NCI and 15 other Institutes with minor components that touch on addiction. CRAN’s administrative structure includes a steering committee composed of the directors of NIAAA, NIDA, and the Director of Prevention Research at NCI. Staff representatives comprise a coordinating committee. A shared cost formula for joint CRAN projects results in 70% of the cost from NIDA, 25% from NIAAA, 4% from NCI, and 1% combined from all other Institutes.

    The Steering Committee has planned three RFAs for FY2014: Administrative Supplements to Promote Collaborative Research on Addiction at NIH (CRAN) for Comorbidity-Related Research, Competitive Revision Applications to Promote Functional Integration for Collaborative Research on Addiction at NIH (CRAN), and Using Social Media to Understand and Address Substance Use and Addiction (R1s and R21s). Additional CRAN activities include website development and a joint NIAAA-NIDA Council meeting in February 2014.

  • Director’s activities. Dr. Warren stated that NIAAA worked with the World Health Organization in Namibia on training for a WHO project to study the extent of fetal alcohol spectrum disorders (FASD) in low- and middle-income countries where heavy alcohol consumption is common. Dr. Warren visited three major FAS-related programs in South Africa that are making great progress, and he presented to the entire medical school student body and faculty at the new University of Namibia School of Medicine.
  • NIAAA staff additions. Dr. Beverly Ruffin and Dr. Brett Hagman were appointed as Health Science Administrator in the Division of Epidemiology and Prevention Research and Division of Treatment and Recovery Research, respectively. Mr. Macy McRae, III, joined NIAAA as a Senior Administrative Officer, and Ms. Julie Simonds was appointed Extramural Support Assistant in the Division of Treatment and Recovery Research.
  • Staff honors. Dr. Beata Buzas received the 2012 NIH Director’s Award for her work with the Research Policy Committee’s Scientific Review Officer Technical Competencies Team. Dr. Richard Rippe received the 2013 NIH Director’s Award for his work as part of the Enhancing Peer Review Survey Consultant Group. Dr. Marcia Scott received a 2012 NCI Director’s Merit Award related to her work on the NIH Genes, Environment, and Health initiative and on the GEI Exposure Biology Program Subcommittee, and as a Project Scientist for the GEI Exposure Biology Network on Exposures to Psychosocial Stress and Addictive Substances. By unanimous vote Dr. Steve Vogel received tenure from the NIH Central Tenure Committee.
  • Director’s Page. Dr. Warren reported that in a large-scale study conducted through NIAAA’s NCIG Program, the smoking cessation drug varenicline (Chantix®) has shown promise as a viable treatment option for alcohol dependence.
  • Communications. Dr. Warren described NIAAA’s graduation and summer safety billboard project to combat underage drinking. A billboard in Somerset County, Maryland—a main route to the beach area—urges travelers to have a safe and sober senior week.  The NIAAA Graduation Fact Sheet was picked up by many newspapers and other media outlets nationwide. Alcohol Alert, No. 85, a new fact sheet on alcohol overdose appears on the NIAAA website and the RethinkingDrinking.com website recently registered its 1 millionth visitor. Staff have also given media interviews to many outlets.
  • Selected NIAAA staff activities and events. NIAAA observed Take Your Child to Work Day and the National Museum of Health’s Brain Awareness Week, and Dr. Bankole Johnson presented the Jack Mendelson Honorary Lecture.
  • Upcoming events. Many NIAAA employees are to attend the upcoming Research Society on Alcoholism conference, and NIAAA plans to release its Guide to Treatment for Alcohol Dependence for the public.

 

Contract Opportunity Concept Reviews

Dr. Warren explained that Council members would have an opportunity to comment on three contract opportunity concept reviews, a procedural requirement prior to issuing a request for proposals.

 

NIAAA Clinical Investigations Group (NCIG) Program

Dr. Raye Litten presented a review of the successful NIAAA Clinical Investigations Group (NCIG) program. NCIG provides a rapid, efficient, and standardized mechanism to conduct proof-of-concept trials and to bridge the gap between preclinical studies and Phase 3 studies, provide valuable efficacy and safety information, deliver a standard of conduct and measurement, and encourage the private sector to consider alcohol indications during early stages of development. Strategies to work with the private sector include risk reduction to pharmaceutical partners by cost sharing, negotiation on intellectual property and publications, and sharing data sets with the public for secondary analysis. NGIC’s advantages include rapid turnaround of results, standardization and support in advertising, staff training, an assessment battery, and trials conducted in accordance with good clinical practice to enable data use in drug development. The program’s structure involves multiple oversight mechanisms and organizations.

NCIG has conducted three clinical trials. A 2008 trial for quetiapine (Seroquel XR®) found no signal, and results were published in Alcohol: Clinical and Experimental Research (ACER). Similar results emerged from a 2009 study of levetiracetam XR (Keppra XR®), and the study generated another ACER publication. A commentary in that same issue suggested this study’s importance.  NCIG’s translational trial for varenicline generated a positive signal and an effect size of 0.35, and worked equally well in smokers and nonsmokers.

NCIG’s has just launched its fourth study, a novel compound with potential indications for depression. Dr. Litten observed that NCIG is attracting many pharmaceutical partners for future work, and two companies have offered NIAAA novel compounds. NCIG intends to continue to improve the process.

Dr. John Krystal, former Council member, and Professor at Yale University endorsed the NCIG program and acknowledged its rapid successes. He observed the program’s extreme importance to a field that previously had no pathways to drug development for alcohol despite corporate interest. NCIG studies constitute an important percentage of all new medications tested for alcohol in the past 5 years. He urged NCIG to talk with companies about their compounds under development and what might be directed to studies of alcohol. Dr. Krystal noted that Institutes use varied strategies to bring drugs into clinical trials and that the NCIG strategy is less common. He questioned what represented the optimum scale of this type of research, and suggested that NCIG develop and evaluate biomarkers or treatments that might guide personalized medicine.

Dr. Litten stated that the compound selection process can be made more transparent and suggested that a Council member and NIAAA internal scientists might become more involved in the process. He concurred with Dr. Krystal on developing a biomarker strategy, noting that NCIG had begun to take genetic samples in the varenicline study. He stated that though imaging is too expensive at this point, NCIG will look at genetic samples in the future.

Dr. Craig McClain concurred with Dr. Krystal’s remarks, noting that it is critical for NIAAA to undertake this project to bring drugs into clinical application and to market. He noted, however, that the project has had difficulties with sample storage and creating a common data management system.

In response to questions posed by Dr. McClain, Dr. Litten stated that NGIC will retain samples for future biomarker testing and will add other features to the program. He solicited information regarding storage strategies and investigation of other markers, including markers related to the immune system, and Dr. McClain observed that markers for organ injury also may be useful. Dr. Litten stated that NCIG chooses study sites according to set criteria and plans to publicize that process with added transparency. Though NCIG has not used Department of Veterans Affairs’ sites to date, that is possible for future studies, for example, on organ damage. NIAAA enjoys functional integration with NIDA through NCIG’s work.

Discussion. Dr. Fulton Crews suggested that NCI may have interest in participating in studies of drugs that address both smoking and alcohol, and encouraged NIAAA to issue integrated RFAs. Dr. Gyongyi Szabo suggested that opportunities exist to extend NCIG’s work to help the field understand the role of general organ effects and interactions between organs, and that NIAAA convene a network of institutions that collect data and patient information on both brain inflammation and alcoholic hepatitis. NIAAA also might extend its work with pharmaceutical companies on other organs where similar etiologic mechanisms may be at play. Dr. Litten acknowledged the possibility of exploring targets with translational research. Dr. Kathleen Grant commented on the opportunity for feedback to preclinical studies Dr. Messing identified the need for resources and initiatives to do early translation as an important research gap, a topic he and Dr. Litten plan to pursue. In response to Dr. Suzanne de la Monte’s question about strategies to choose targets, Dr. Litten stated that drugs must be at a certain stage of development before becoming eligible for NCIG studies. Many targets affect drinking behavior, and the key is to determine interrelationships, how to address addictions’ various components, and combinations of targets for more people to respond to medications.

Dr. Howard Moss stated that NIAAA is working to develop a full pipeline for medications development. Preclinical screening using animal assays and a human laboratory to serve as an intermediary between NIAAA’s preclinical screening program and clinical trials, once implemented, it will constitute a seamless translational program from bench to bedside to examine and vet new compounds. NIAAA is interested in medications development for organ damage as well as the behavioral aspects of alcohol dependence, and in a bio bank that makes samples from clinical trials available to investigators interested in biomarker development.

 

Animal Models

Dr. Phillip Brooks, Program Director, Division of Metabolism and Health Effects, NIAAA, presented NIAAA’s concept for a contract regarding alcohol-related mammary cancers. To provide a foundation for mouse models of alcohol-related breast cancer, Dr. Brooks stated that NIAAA proposes to initiate a contract to reproduce, under carefully controlled, highly replicable conditions, a pivotal animal study by Watabiki et al. (Alcohol. Clin. Exp. Res. 2000; 24(4):117S-122S) that generated mammary tumors in 45% of mice given alcohol in drinking water over 2 years. Deliverables will include study data and the tumor and control tissues of the animals, to enable genetic and genomic analyses. Dr. Brooks noted that high-impact journals have begun to appreciate the importance of reproducibility. NIAAA plans to publish results and make data available to the community.

Discussion. Dr. Carol Casey pointed out the dearth of good animal models for alcohol and cancer, including liver cancer, and suggested consideration of studies that incorporate the Lieber-DeCarli diet. Dr. Crews urged investigators to visit the original vivarium to maximize replication factors, keeping in mind significant gene/environment interactions. Dr. Brooks described current thinking on animal diet and acknowledged that animal strains drift over time. Dr. Grant expressed concern over the typical response by the field to a replication study, which is to selectively cite literature in the context of how they see the field. She also observed that if results are not replicated, questions might arise and the findings might change the designation of ethanol as carcinogen or factor in breast cancer; Dr. Brooks expressed doubt that study results would affect the classification. Dr. Szabo commended NIAAA for considering investigating alcohol and cancer interactions, but urged caution about the importance of the study, which had received little attention. Dr. de la Monte also cautioned about strain drift and an inability to truly replicate the study. She noted that many epigenetic events might have taken place in a study that apparently did not monitor all organs. Any remaining tissue from the study might be examined for changes. Dr. Brooks responded that the baseline level was zero for mammary tumors in the mouse strain used. Dr. McClain added that all the male mice fed alcohol developed fibrosis. Dr. Crews stated that the increase in breast cancer due to moderate drinking was an exceptional finding; all other cancers are associated with much heavier drinking types of phenotypes. In response to a question from Dr. Szabo, Dr. Brooks stated that it matters whether alcohol is a promoter or complete carcinogen; if alcohol is a promoter it acts on already activated cancer cells, but if there is no carcinogenic process, a person is not at risk for alcohol-related breast cancer.

 

Bilingual Database for Alcohol-Related Research

Dr. Judith Arroyo, NIAAA Minority Health and Health Disparities Coordinator, presented a concept proposal to create a database of alcohol research-related measures available in languages other than English. NIAAA Council members had urged NIAAA to enhance recruitment of non-English-speaking study participants, and the question arose about whether or not the availability of measures commonly used in alcohol studies in languages other than English affected both recruitment into clinical research and discouraged people from participating.

The project would seek to identify currently existing non-English measures by conducting a literature search back to 1990.  Reports of research that suggested measures were available to non-English language speakers would be included in the data based.  The contractors would contact the authors to obtain information about measure or copies of measure where possible. Deliverables in this cost-effective effort to increase the diversity of NIAAA study subjects would include a 504-compliant database with copies of the measures or contact information about potential sources of measures, and basic information about the measures, including psychometric data, if available, and demographics of the populations with which the measures have been employed. The project also would document the protocol used to collect the information and establish the database to facilitate updates. The database, which would include measures in as many languages as possible, may enhance investigators’ willingness to include diverse samples and foster the study of acculturation level, which has been found to affect participation and alcohol use.

Dr. Andres Gil advised that the project will enable alcohol researchers working with Spanish-speaking populations, for example, to use already validated measures. The existence of the database has potential to increase the number of people who conduct research with non-English-speaking populations and to minimize IRB concerns.

Dr. Paul Gruenewald expressed appreciation for the proposal’s potential to direct the field toward studies of unique subpopulations in the United States and new immigrant populations. He expressed concern that though emphasis is placed on Spanish speakers noting that genetically informative populations are in Southeast Asia among other places. He raised the issue of cultural appropriateness of items on these scales, about which the proposed effort may shed illumination.

Discussion. Dr. Molina suggested limiting the number of languages, and Dr. Gruenewald concurred. Dr. Molina stated that validated Spanish-language measures for persons with low educational level represent a great advance for the field. She noted the importance investigators addressing minority populations in their study designs. Dr. McClain suggested the value of consent forms translated into Spanish for any NIAAA-funded clinical trial to expedite IRB action.

Some Council members discussed difficulties in translating measures. Dr. Gil responded that the proposed database will make research easier to conduct. Dr. Gruenewald noted that larger-scale epidemiology studies to assess the percentage of the population with a certain alcohol disorder may be subject to variability in interpretation; cultural differences represent a significant issue for delivery of health resources. Dr. Barthwell raised a concern that minority representation was not likely to be increased by the use of non-English measures but by increasing the diversity of research staff.  Dr. Arroyo pointed out that NIH aims to increase the diversity of biomedical workforce. She clarified that the project would identify and catalog available measures and would not include the translation of measure not already available. Inclusion of any particular measures in the database would not constitute endorsement. Dr. Arroyo acknowledged the value of helping IRBs to approve research and also the value of enabling proper research with diverse populations. Dr. Gary Murray stated that this project represents a small business opportunity. Dr. Arroyo added that NIAAA had asked the Library of Science for a cursory review of the literature.  This effort did not yield results so that it appears necessary to read the literature itself.

 

Presentation of Council Operating Procedures

Council members unanimously approved the Council Operating Procedures (see Appendix 1*) for administrative actions by program staff that do not require Council action, special Council review of grant applications over the $1 million direct cost threshold, and the early concurrence protocol.

 

Consideration of the February 6–7, 2013 Meeting Minutes and Future Meeting Dates

Council members unanimously approved the minutes of the NIAAA Council meeting held February 6–7, 2013.

Future meeting dates include September 18–19, 2013: February 5–6, 2014, including a Joint NIAAA/NIDA (and possibly NCI) meeting; June 4–5, 2014; September 10–11, 2014; February 4–5, June 10–11, and September 16–17, 2015.

 

NIAAA Consortia for HIV/AIDS and Alcohol Research Translation

Dr. Kendall J. Bryant, NIAAA HIV/AIDS Coordinator, explained that NIAAA’s five alcohol-HIV/‌AIDS consortia are part of a $3 billion NIH research program structured by a complex array of cooperative agreements. Dr. Bryant explained that alcohol use is a driver of the HIV epidemic in many places and among many subpopulations at greatest risk for infection. Alcohol increases susceptibility to HIV infection and prevalence in certain populations (such as young gay men), and it changes how HIV is expressed in the host and the host’s immune response, in the progression of the disease in both past and present alcohol use, and in the availability and adherence to lifesaving antiretroviral medications. This cumulative history impacts rates of mortality, organ failure, marginalization of treatment, and stigmatization of minority populations. With these consortia NIAAA is developing the research structures needed for the present and future and the methodologies necessary for prevention and treatment.

Established in 2011, the Consortia for HIV/AIDS and Alcohol Research Translation (CHAART) bases its work on 20 years of research. Dr. Bryant noted that the most common substances used by people infected by HIV are alcohol and cigarette smoking, making the discovery of varenicline as an effective treatment a potentially important advance.

Dr. Bryant explained that currently 34–40 million people worldwide live with HIV/AIDS, with 2.5 million new infections and deaths from HIV at 1.7 million. In the United States 1.3 million people are infected and 40,000–60,000 new infections are recorded annually; the estimated annual rate of infection directly related to alcohol is 10–20%. It is hypothesized that widely distributed, simple alcohol treatments could reduce the new infection rate by 4–8%, and that integrating alcohol interventions with systems of care could reduce rates of new infections, particularly in minority populations. The Centers for Disease Control and Prevention (CDC) reports that nearly two thirds of new infections in the United States occur in gay and bisexual men, and among African-American men and women, signaling the need to target minority populations for alcohol interventions.

NIAAA has published Alcohol Alerts, a research protocol for India, and other materials. Dr. Bryant stated that only 25% of individuals in the United States effectively suppress their virus, while 75% are actively untreated or have failed treatment. NIAAA has placed emphasis on implementation or operations research to engage people in treatment, which also serves as a preventive intervention. Dr. Bryant enumerated the three components of an alcohol and HIV/AIDS consortium: comprehensive clinical cohort assessment, dynamic interventions, and collaborative research.

 

Alcohol & HIV/AIDS Consortia Progress Reports

Dr. Amy Justice, Director, Consortium to improve Outcomes in HIV/AIDS, Alcohol, Aging, and multi-Substance Use (COMpAAS), stated that COMpAAS’s work represents an extension of the Veterans Aging Cohort Study (VACS), a longitudinal study, funded in part by NIAAA, of more than 40,000 HIV-positive individuals demographically matched to 80,000 uninfected controls that has generated extensive data on alcohol and multi-substance use. The project leverages the VA’s electronic medical record system and adds to the database.

COMpAAS asks critical questions regarding HIV-positive individuals who drink alcohol: Is any pattern of use physiologically safe? To what extent does alcohol use reinforce smoking, non-adherence, risky sex, and depression? Does multi-substance use impact harm from alcohol use? And, how should pattern of alcohol use alter choice of intervention? The consortium’s coordinating center aims to guide observational, intervention, and/or modeling research to develop optimized care for HIV-infected individuals harmed by alcohol, multi-substance use, hepatitis C, and depression; provide support and coordination to the expert network to facilitate rigorous project review and monitoring to maximize the scientific impact; and develop a Web-based laboratory to support ongoing research and facilitate external validation and dissemination of findings.

Dr. Justice explained that the consortium’s organization involves cores for operations research, alcohol and behavioral intervention, medical informatics, biostatistics, and content cores that currently include cancer, and cardiovascular, liver, and pulmonary disease all of which have garnered independent funding. Workgroups on topics of interest have become new cores as they have garnered funding, and the project has involved many research trainees. The consortium collaborates not only with NIAAA but also with other investigators in the HIV arena to create interest in research on alcohol and substance use and to facilitate comparison of data across studies. COMpAAS has a tissue and DNA repository and has just been funded to obtain serial samples on antiretroviral therapy- (ART) naïve as well as demographically similar uninfected new enrollees. The consortium currently has 91 projects at various stages in the pipeline and hopes to extend its mechanism and organization to other related consortia. Additional COMpAAS features include a website and a VACS Risk Index Calculator.

The coalition’s observational work recently began electronic conversion of its survey, continues the enrollment process, generates potential interest among enrolled patients to participate in additional online studies, and is beta testing an electronic, multi-substance timeline follow-back tool. VACS and COMpAAS has generated 213 publications and more than 5,000 citations for the study. Dr. Justice stated that COMpAAS’s responses to methodological challenges in observational work include measurement of alcohol and related exposures, devising personalized measures of harmful use, and accounting for study subjects who stop drinking when they become ill. Investigators find that personalized measures of alcohol are more closely correlated with adherence than the conventional threshold for alcohol consumption and therefore can better identify people likely to be non-adherent to ART. Preliminary data show a full drink difference among HIV-positive individuals in every age group, compared to HIV-negative individuals, in their thresholds to “drinks to get a buzz” and to feel drunk or out of control. Alcohol use continues into older age among HIV-positive versus uninfected individuals, and tolerance is likely reduced. In addition, the VACS index has been developed to provide an integrated measure of risk of multifaceted physiologic harm to which aging, alcohol consuming, HIV infected individuals are subject.

The VACS index, based on routinely available and measured clinical markers, and validated with controls (assuming normal CD4 and an HIV-1 RNA of 0) as well as HIV-positives, is more highly predictive of mortality among a wide range of populations than age, CD4, and HIV-1 RNA alone; is more correlated with inflammatory biomarkers; predicts other clinical outcomes more accurately, including cognitive performance; and is responsive to changes in physiologic status. Changes in the score from treatment initiation also are highly predictive of mortality. Investigators used the index to look at estimated risk of 5-year mortality based on alcohol use; risk of mortality rises with the level of alcohol consumption, particularly as people age. The consortium’s electronic laboratory includes a tool to calculate and interpret an individual’s index.

The Integrated Stepped Care for Unhealthy Alcohol Use in HIV project, led by Dr. David Fiellin is recruiting participants in order to compare integrated stepped care versus treatment as usual. Primary outcomes are alcohol consumption, at-risk drinking, alcohol abuse and dependence, drinks per week over the last 28 days at 6 months, moderate alcohol, and liver disease. A secondary outcome will be VACS index change to show that the index is responsive to intervening on alcohol. The ultimate goal is a randomized controlled trial that gives participants a personalized estimate of health improvement options that take into account patient preferences and readiness to change. The menu will include smoking cessation, alcohol treatment, and depression treatment, which people can consider to make personal decisions about future actions.

The Operations Research Modeling to Optimize Intervention Design project, led by Dr. Scott Braithwaite, is currently conducting the data analyses required to inform an update to Dr. Braithwaite’s combined patient level and population level operations model.  Their goal is to create a “value of information tool” that would help decision makers (including NIAAA among others) decide on the appropriate priority directions in the domain of alcohol and health outcomes as related to HIV infection.  This group is meeting biweekly with Dr. Justice’s team to insure fidelity to the data analyses and appropriate interpretation of results.

Dr. Samet joined NIAAA scientists on a 1999 visit to Russia.  At that time the HIV epidemic was relatively new in Russia but the situation was compounded there in an alcohol context by the country’s heavy alcohol consumption rates.   The investigators found that among 200 HIV-infected Russian inpatients, alcohol dependence was present in nearly half. The Partnership to Reduce the Epidemic Via Engagement in Narcology Treatment (PREVENT) surveyed 181 Russian narcology patients, of whom 15% had HIV infection, and they adapted and conducted a randomized intervention to decrease unsafe sex that was found to be highly effective among alcohol patients. The ongoing HERMITAGE study, a randomized controlled trial of a behavioral intervention to decrease unsafe sex, alcohol and drug use, and sexually transmitted infections among Russian HIV-infected risky drinkers, found no significant differences between controls and the intervention group; everyone improved between baseline and follow-up.

Dr. Samet described the themes of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium, which examined from an international perspective the consequences of alcohol on HIV disease and how to mitigate its harmful effects. URBAN ARCH is supported under the Cooperative Agreement mechanism (U01) that involves coordination between Boston, Uganda, and Russia.  This consortium also has an administrative core and a biostatistics data management core.

Alcohol use is now recognized in a worldwide context, as an important issue in the quest to contain and address .  One aspect of this association is alcohol’s impact on adherence to ART. The URBAN ARCH Uganda cohort is asking whether heavy alcohol consumption accelerates HIV disease progression in ART-naïve HIV-infected individuals. Uganda has been a useful country for this research effort because of its welcoming environment coupled to its high rate of alcohol consumption. The study is providing valuable data in the identification of important biomarkers for alcohol problems and HIV pathology.  

The URBAN ARCH cohort in Boston is asking whether alcohol use is associated with decreased bone density among HIV-infected drug users. Osteopenia is a comorbid issue with HIV; bone and alcohol interactions have not yet been looked at carefully in HIV. Enrollment is underway, and investigators also will investigate whether high-dose buprenorphine/naloxone can reduce heavy drinking days compared to the standard dose at 3 months.

The URBAN ARCH cohort in Russia includes longitudinal studies that are anticipated to produce valuable information on alcohol and HIV.  The project is asking whether or not heavy alcohol use is associated with elevated inflammatory markers in ART-naïve HIV-infected individuals. By taking advantage of multiple cohorts URBAN ARCH can explore the association between heavy alcohol use and inflammatory markers, and can determine the association between heavy alcohol use and bone turnover using biomarkers.

URBAN ARCH’s ZINC randomized controlled trial (RCT) is a double blind study of zinc supplements among HIV-infected ART-naïve, heavy drinkers in Russia.  It has the goal of improving markers of mortality, slowing HIV disease progression, improving markers of acute myocardial infarction risk, and decreasing microbial translocation and inflammation.

Dr. Samet highlighted URBAN ARCH’s successes in research career training. He acknowledged NIAAA’s support and suggested that the NIDA International Program INVEST plays a role in NIAAA’s collaborative future with NIDA.

Discussion. Dr. Samet responded to a question from Dr. Crews that he believes the alcohol/cognitive function/HIV story is in its infancy, but URBAN ARCH has not conducted substantial research in that area. Dr. Kendall added that the consortium involving Brown University and the University of Florida has a larger cognitive component. Dr. Justice explained that COMpAAS is doing a collaborative analysis on whether or not the VACS index can be used as a threshold for starting screening for cognitive performance.

 

Ex-officio Member Reports

Dr. Dan Kivlahan, Department of Veterans Affairs, reported that the VA recently awarded seven inter-professional fellowships in addiction treatment. He stated that the VA has capitalized on some NIAAA-funded work to accelerate adjustments to its pharmacy benefits criteria. The agency has modified the use of acamprosate to be less restrictive, and the VA will look next at revisiting the use of injectible naltrexone and invited NIAAA input. The VA welcomes guidance on how DSM-5 changes may affect FDA indications for medications and research studies.

Dr. Kivlahan stated that the VA recognizes the need for more evidence-based approaches to address gambling disorders among a broad population in multiple settings. The VA is trying systematically to implement measurement-based care in its specialty programs. Both the VA and the Department of Defense (DoD) are receiving demands from external stakeholders, including Congress, to identify whether their populations are improving from the services they receive to become healthier and better functioning. The VA is making progress using the clinically oriented Brief Addiction Monitor. Dr. Kivlahan asked Council members for input on a proposal by the Department of Defense to use the 10-item Alcohol Use Disorders Identification Test (AUDIT) Alcohol Screening Instrument as a measure of treatment response. Dr. Warren noted that Council members endorsed Dr. Kivlahan’s concern about the AUDIT is not an appropriate instrument  for post-alcohol treatment evaluation and both he and the Council wished Dr. Kivlahan well in his effort to correct this error in the DoD.

Dr. Warren observed that the Department of Defense ex-officio position remains vacant.

 

Public Comment

Time was set aside for public comment, but no one stepped forward to speak.

 

Adjournment

The meeting adjourned at 12:50 p.m.

 

CERTIFICATION

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

 

/s/

Kenneth R Warren, Ph.D.

Acting Director

National Institute on Alcohol Abuse and Alcoholism

and

Chairperson

National Advisory Council on Alcohol Abuse and Alcoholism

/s/

Abraham P. Bautista, Ph.D.

Director

Office of Extramural Activities

and

Executive Secretary

National Advisory Council on Alcohol Abuse and Alcoholism