OARAC Meeting Minutes

Office of AIDS Research Advisory Council
Twenty-Seventh Meeting
October 24, 2008

National Institutes of Health
U.S. Department of Health and Human Services
Hilton Gaithersburg
Gaithersburg, Maryland

Members Present: Dr. James W. Curran (Chair), Dr. Jack Whitescarver (Executive Secretary), Ms. Dawn Averitt Bridge, Dr. Sharon E. Frey, Dr. Gary W. Harper, Dr. Betsy C. Herold, and Dr. Michael F. Summers

Ex Officio Members Present: Dr. John G. Bartlett, Dr. Diana M. Lopez, and Dr. Christel H. Uittenbogaart

Ad Hoc Members Present: Dr. Daniel J. Raiten and Dr. Paul A. Sato

Invited Speakers and Guests: Dr. Pim Y. Brouwers, Dr. Lawrence M. Fox, Dr. Rohan Hazra, Dr. Bonnie J. Mathieson, and Dr. Christine A. Wanke

Welcome

The National Institutes of Health (NIH) Office of AIDS Research Advisory Council (OARAC) convened its twenty-seventh meeting at 1:30 p.m. at the Hilton Gaithersburg in Gaithersburg, Maryland. Dr. James W. Curran, Chair, welcomed the OARAC members, invited speakers, and guests.

The topic of the meeting was Nutrition and the Clinical Management of HIV. A workshop entitled Identifying Priority Research Questions on the Interaction of Nutrition and the Clinical Management of HIV/AIDS, co-sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), immediately preceded the OARAC meeting, and OARAC members were invited to attend. The Working Group findings from the Workshop were presented at the OARAC meeting. The OARAC members and the invited guests discussed the findings and priorities for future research.

The minutes of the April 17, 2008 OARAC meeting were approved as submitted.

Director’s Report

Dr. Jack Whitescarver, Director of the Office of AIDS Research, welcomed everyone to this meeting of OARAC. He also welcomed Dr. Gary Harper as the newest member to the Council. Dr. Harper is a Professor in the Department of Psychology and Director of the Masters of Public Health Program at DePaul University in Chicago. He also is a member of the Behavioral Leadership Group within the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Dr. Harper previously chaired the American Psychological Association’s Committees on Psychology and AIDS and on Lesbian, Gay, and Bisexual Concerns. Dr. Whitescarver stated that Dr. Harper has worked collaboratively with community agencies and community members to develop and evaluate a range of HIV prevention strategies and programs that target young gay and bisexual men and young women of color. He also noted that Dr. Harper has conducted this work in a range of urban communities throughout the United States, as well as in urban and rural communities in Kenya.

Dr. Whitescarver reviewed several recent personnel changes at NIH. He announced that Dr. Elias Zerhouni, Director, NIH, submitted his resignation effective October 31, 2008, so that he may pursue writing projects and other professional opportunities. Dr. Zerhouni was named the Director of NIH in 2002. Dr. Whitescarver also noted that Dr. Raynard Kington, Deputy Director, NIH, is expected to be named the Acting Director of NIH.

Dr. Francis Collins resigned as Director of the National Human Genome Research Institute (NHGRI) after 15 years of service. Dr. Collins is exploring other writing and professional opportunities and will continue as a special volunteer with the NHGRI Division of Intramural Research. Dr. Whitescarver reported that Dr. Alan Guttmacher, who has held leadership roles at NHGRI for nearly a decade, was named the Acting Director of NHGRI.

Dr. Ting-Kai Li, Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) since November 2002, will retire from federal service effective October 31, 2008. Dr. Kenneth Warren, Deputy Director of NIAAA, will serve as Acting Director of the NIAAA.

Dr. Norka Ruiz Bravo, NIH Deputy Director for Extramural Research and Director of the Office of Extramural Research (OER), will transfer to a new role as Special Advisor to the NIH Director in November 2008. Dr. Sally Rockey, Deputy Director of OER, will serve as the Acting NIH Deputy Director for Extramural Research and the Acting Director of OER.

Dr. Whitescarver welcomed Drs. Daniel Raiten and Paul Sato to the Council meeting as Ad-Hoc OARAC members. Drs. Raiten and Sato co-chaired the Workshop on Identifying Priority Research Questions on the Interaction of Nutrition and the Clinical Management of HIV/AIDS (Workshop on Nutrition and HIV/AIDS) that preceded the OARAC meeting. Dr. Raiten is a Program Officer in the Endocrinology, Nutrition, and Growth Branch of the Center for Research for Mothers and Children at NICHD. He is the project leader for the NICHD project on iron and malaria that is cosponsored by the Bill and Melinda Gates Foundation. He also serves as the Secretariat for two bilateral programs between the United States and India; one on Contraception and Reproductive Health Research and the other on Maternal and Child Health and Human Development Research. He also serves on numerous domestic and international committees, including the World Health Organization (WHO) Technical Advisory Group on Nutrition and HIV/AIDS. Dr. Paul Sato is a Medical Officer in the International Maternal, Adolescent, and Pediatric Branch of the Therapeutics Research Program in the Division of AIDS (DAIDS) at NIAID. Dr. Sato is board-certified in Pediatrics and Preventive Medicine and is a Commissioned Officer in the U.S. Public Health Service. He currently oversees clinical trials of therapeutics for HIV/AIDS through the NIAID-sponsored International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network. He also has extensive international experience, having served in the HIV/AIDS epidemiology and surveillance unit at the WHO and subsequently at the Joint United Nations Programme on HIV/AIDS (UNAIDS).

Conflict of Interest Statements

Dr. Whitescarver asked Council members to review and sign the conflict of interest statement provided to them. He reminded them that NIH policy requires all individuals appointed to serve as Advisory Council members to complete financial disclosure forms and that he is required to certify that all OARAC members have complied with this requirement.

Budget Overview

Dr. Whitescarver reported that NIH will be operating in fiscal year (FY) 2009 under a continuing resolution at the FY 2008 budget level until at least March 2009. He noted that NIH has lost 25 to 30 percent of its buying power over the past several years due to flat budgets and inflation. He reported that the new Congress and new Administration will have to complete both the FY 2009 and FY 2010 budgets next year. The FY 2009 Office of AIDS Research (OAR) Bypass Budget submitted to the Office of Management and Budget (OMB) and Congress included a request for a 15 percent increase to restore funding to the NIH AIDS research program and to address current scientific needs, particularly in the area of prevention.

Meeting Overview

Dr. Whitescarver stated that this OARAC meeting was planned to immediately follow and link with the Workshop on Nutrition and HIV/AIDS organized by NIAID and NICHD and supported by OAR. The Workshop resulted from a meeting of key NIH Institute and Center (IC) staff convened by OAR in May 2007 to explore the research agenda on the interaction of nutrition and clinical management of HIV/AIDS. Dr. Whitescarver noted the three recommendations that emerged from that meeting: 1) integrate nutrition research into current protocols of NIH clinical networks, as appropriate; 2) develop new protocols that address this research topic; and 3) identify gaps and opportunities for future research initiatives and trans-NIH collaborations. He stated that the Workshop on Nutrition and HIV/AIDS was planned to address the third objective.

Dr. Whitescarver noted that the issues around nutrition and HIV disease, both the impact of nutritional status on HIV and vice versa, are of increasing interest and importance. He stated that there is evidence that antiretroviral therapy (ART) has significant nutritional implications, and ART is associated with many metabolic disorders, including abnormalities in lipid, glucose, and bone mineral metabolism. In addition, there are significant nutritional considerations related to pregnancy in HIV-infected women and mother-to-child transmission (MTCT) of HIV. Dr. Whitescarver noted that while it may seem that these issues are most relevant to the international research agenda, it should be remembered that there are many communities across the United States where people are going hungry today.

Dr. Whitescarver stated that the Rapporteurs of the three Working Groups of the Workshop on Nutrition and HIV/AIDS will present a synopsis of the Workshop. He noted that he looked forward to the OARAC members’ lively discussion of the scientific priorities and opportunities for research in the area of nutrition and HIV/AIDS.

Highlights of the AIDS Vaccine 2008 Conference

Dr. Whitescarver noted that at the April 2008 OARAC meeting, Dr. Anthony S. Fauci, Director, NIAID, reported on the findings of the NIAID HIV Vaccine Summit that was held in March 2008. Dr. Whitescarver reported that the research community is already beginning to refocus the AIDS vaccine research agenda on discovery research in light of the Summit recommendations. This new focus was apparent at the AIDS Vaccine 2008 Conference held in Cape Town, South Africa in October 2008. Dr. Whitescarver asked Dr. Bonnie Mathieson, Coordinator of Vaccine Research, OAR, to present a summary of the highlights of the meeting.

Dr. Mathieson noted that there was an emphasis on HIV transmission research at the AIDS Vaccine 2008 Conference. She described the results from two studies aimed at understanding the compartmentalization of HIV in the body and identifying the source of transmitted virus. She cited recent findings that the transmitted virus appears to originate from the plasma compartment in discordant couples.

Dr. Mathieson reported that researchers investigating host genetics have identified at least six genes that may be important for HIV transmission and disease progression. Several additional genome-wide association studies are ongoing.

Dr. Mathieson described reports that indicate HIV immune-escape epitopes occur early in the course of infection. She stated that these results highlight the need to identify conserved epitopes to use in the design of new vaccine vectors and constructs. Dr. Mathieson summarized a research report of an interaction between epitopes from the V1-V2 region with gp41 epitopes under conditions where one epitope alone is not sufficient for neutralization. Dr. Mathieson noted similar findings have been reported for epitope interactions and emphasized the importance of these results for future vaccine research.

Dr. Mathieson reported on the results from several studies in animal models, including a study on the fate of immune cells following vaccination with the cytomegalovirus (CMV) vector. Cells with an effector-memory phenotype were identified within the gastrointestinal tract and other tissue that appear to be effective in generating protective immunity following HIV challenge.

Dr. Mathieson summarized a report on DNA vaccine vectors. The DNA and adenovirus vectors from the recently halted Merck STEP trial were reengineered by adding additional HIV components. In animals vaccinated with the DNA vaccines, up to 20 epitopes have been identified in individual animals, and some vaccinated animals were protected from a heterologous challenge. Dr. Mathieson also described the results from a study of a protein-based vaccine administered following priming either with a DNA vector vaccine or a pox vector vaccine that generated neutralizing antibodies with a sustained elevation in antibody levels with expanded breadth of neutralization.

Update on OARAC Working Groups for Treatment and Prevention Guidelines

Dr. John G. Bartlett, Professor of Medicine and Chief of Infectious Diseases at the Johns Hopkins University School of Medicine and Co-Chair of the Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents, presented an update on the activities of the OARAC Working Groups for Treatment and Prevention Guidelines.

Dr. Bartlett reported that the revised guidelines for treatment and prevention of opportunistic infections (OIs) in HIV-infected individuals were released in June 2008. They were developed through a collaborative effort among NIH, the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America. The guidelines were divided into two categories and released as two separate documents: Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents and Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Children. He noted that the decision to publish the guidelines as two documents was made because there are unique considerations for HIV-exposed and -infected children that have implications for OI prevention and treatment. Dr. Bartlett reported that 700,000 online copies of the revised OI guidelines were downloaded from AIDSinfo (www.aidsinfo.nih.gov) in July 2008. He also noted that it is anticipated that these documents will be published in Morbidity and Mortality Weekly Report in November 2008.

Dr. Bartlett stated that the updated guidelines address prevention of OIs; clinical features of OIs; diagnostic methods; treatment modification for pregnancy; drug interactions; prognosis; timing of the initiation of ART in the presence of a current or recent OI; and immune reconstitution inflammatory syndrome (IRIS). The revised guidelines also contain extensive reference tables on OI treatment; primary and secondary prophylaxis; when to discontinue prophylaxis; and drug interactions and toxicities. Dr. Bartlett stated that although the guidelines focus on patients in the United States, they address OIs such as Chagas disease, leishmaniasis, and malaria that may occur in immigrants and international travelers.

Dr. Bartlett reported that the updated Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents includes an expanded discussion of treatment options for hepatitis B virus (HBV) and an expanded diagnostic review of tuberculosis (TB), including a discussion of gamma interferon release assays. The guidelines also discuss immunization of HIV-seropositive individuals against HBV, influenza, and pneumococcus; and OIs predominantly found in specific geographic regions.

The Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Children discuss OIs not included previously, including asperogillosis; bartonellosis; human herpesvirus 6, 7, and 8; malaria; and progressive multifocal leukoencephalopathy. They also discuss IRIS; initiation of ART in the presence of acute OIs; and the use of the new meningococcal conjugate vaccine, the HBV vaccine, and the rotavirus vaccine.

Dr. Bartlett stated that the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were last updated in January 2008 and that the next revision is expected to be released in November 2008. Dr. Bartlett noted that the Working Groups for Treatment and Prevention Guidelines anticipate making interim revisions to online versions of various guidelines in the future. He stated that the online versions soon will be downloadable by individual section.

Dr. Bartlett stated that revisions to the Guidelines for Perinatal Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States were released in July 2008. Dr. Bartlett reported that these guidelines have new tables on antepartum and neonatal ART dosing and recommendations for the use of Nelfinavir.

Dr. Bartlett reported that the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection were updated in February 2008. The guidelines discuss newly approved drugs for children; recommendations on the use of Nelfinavir; timing of ART initiation; and new dosing information for several protease inhibitors.

Dr. Bartlett acknowledged the more than 250 Working Group members who have contributed to the recent guideline updates.

Overview of the Workshop on Identifying Priority Research Questions on the Interaction of Nutrition and Clinical Management of HIV/AIDS

Dr. Curran introduced Dr. Christine Wanke, Professor, Tufts University School of Medicine and Co-Chair of the Workshop on Nutrition and HIV/AIDS. Dr. Wanke presented an overview of the Workshop. She noted that, historically, many infectious disease physicians have not adequately appreciated the importance of nutritional and metabolic complications in HIV-infected people. Dr. Wanke stated that the Workshop provided an excellent forum for discussion of the current evidence-base and the identification of priority research questions related to the interaction of nutrition and HIV/AIDS.

Dr. Wanke discussed five important crosscutting and overarching areas that were identified at the Workshop for which additional research is needed. All of these areas are relevant both domestically and globally.

Dietary quality and content in HIV-infected individuals who either are under-nourished or over-nourished (overweight/obese): Specific nutrients can alter metabolism, physiology, inflammation, and immunity and can influence medical outcomes. Dr. Wanke provided examples, including the effects of micronutrients, macronutrients, and various types of fat on inflammation and metabolism; the effects of various types of protein on lean body mass and growth; and the effects of micronutrients on immune function and physiology.
Intestinal microflora and intestinal integrity in HIV-infected populations: Dr. Wanke stated that this research is needed to address the basic, clinical, and translational science issues related to the ingestion, digestion, absorption, and metabolism of nutrients. She cited examples, including the effects of intestinal microflora on the absorption and metabolism of antiretrovirals (ARVs).
Development of standardized methodologies to accurately assess nutritional and metabolic parameters in specific regions of the world: Dr. Wanke noted the importance of applying these measures to existing cohort studies to assess nutrition-related study endpoints and/or to monitor responses to interventions.
Optimal timing of nutritional interventions and ART in populations affected by HIV and malnutrition.
Impact of food insecurity on dietary quality and medical outcomes, adherence and response to ART, depression, HIV transmission risk, and the sustainability of nutritional or metabolic interventions.

Discussion of Research Priorities Identified by Working Groups at the Workshop on Nutrition and HIV/AIDS

Dr. Curran reported that the Workshop on Nutrition and HIV/AIDS consisted of a series of presentations followed by discussions in Working Groups. Dr. Curran introduced the Rapporteurs of the three Working Groups and noted the topic on which each would be reporting: Dr. Lawrence Fox, Senior Medical Officer, HIV Research Branch, Therapeutics Research Program, DAIDS, NIAID: nutrition and HIV/AIDS research priorities for adult populations; Dr. Rohan Hazra, Medical Officer, Pediatric, Adolescent, and Maternal AIDS Branch, NICHD: research priorities for children and adolescents; and Dr. Pim Brouwers, Associate Director of the Infant, Child, and Adolescent Research Programs and Chief of the Primary Prevention Branch, Center for Mental Health Research on AIDS, Division of AIDS and Health and Behavioral Research, National Institute of Mental Health: the contextual issues and comorbidities in nutrition and HIV/AIDS research.

Dr. Fox noted that all three Workshop Working Groups discussed the same topics. The Working Group Chairs and Rapporteurs met afterwards to synthesize one set of priority research questions for each topic.

The Working Groups were asked to:

Identify priority research questions on the interaction of nutrition and the clinical management of HIV/AIDS that are potentially answerable through well designed observation studies, analyses of existing datasets, and/or controlled intervention trials.
Identify how the current NIH-funded AIDS research infrastructure can best be engaged in answering knowledge gaps and determining how to optimally integrate food and nutrition into the clinical management of HIV/AIDS and related comorbidities.
Identify the priority issues for further scientific investigation, with special emphasis on resource-constrained settings.

Priorities for Adult Populations

Dr. Fox stated that the new paradigm for HIV pathogenesis includes the role of nutrition (under-nutrition and over-nutrition) and the effects of gut microflora and intestinal integrity on microbial translocation. He stated that the most urgent questions focus on the impact of macronutrient and micronutrient malnutrition on HIV disease progression; ART response, adherence, and toxicities; and risk of HIV acquisition and transmission.

Dr. Fox noted that all three Working Groups agreed on the need for standardized methodologies that can be utilized in resource-limited settings to accurately assess specific nutritional and metabolic parameters. He noted that some HIV clinics may have trouble obtaining even simple equipment, such as a scale, and he questioned whether more sophisticated measures, such as dual energy X-ray absorptiometry (DEXA) scans, could be performed in some resource-limited settings.

Dr. Fox stated that the Working Groups also identified the following priority research questions for the study of nutrition and HIV/AIDS in adults:

Timing and Content of Nutritional Supplements:

When should nutritional supplementation be initiated in HIV-infected individuals who are malnourished? What markers of nutritional status should inform this decision?
What are the appropriate local norms against which to measure malnutrition in HIV-infected individuals?
What nutritional supplements are indicated for HIV-infected individuals who are malnourished? What is the optimal composition for supplements based on calories from fat, carbohydrate, and protein?
When should ARV therapy be initiated in patients receiving nutritional supplementation for malnutrition?
How does HIV and TB coinfection affect the optimal timing of nutritional and ART interventions in malnourished individuals?
When should the treatment plan change from treatment of acute malnutrition to treatment of moderate malnutrition?
When should treatment with nutritional supplementation be terminated? What markers of nutritional status (e.g., HIV status, comorbidities, etc.) should inform this decision?

Body Content and Biologic Issues:

What is the optimal body-mass index (BMI) and nutritional status for HIV-infected individuals?
What is the optimal diet for HIV-infected individuals who have metabolic abnormalities, including obesity?
What is the increased energy requirement for HIV-infected individuals? Is the WHO recommendation for a 10-20 percent increase in energy requirement valid for HIV-infected individuals?
What are the risks of refeeding syndrome in malnourished HIV-infected individuals?
What is the pathophysiologic difference(s) between starvation and cachexia induced by HIV and/or TB? What biomarkers can be used to differentiate between starvation and cachexia?
How does the intestinal microflora impact nutrition; how is it impacted by nutrition; and what are the effects of gut microflora on intestinal integrity?
To what extent is malnourishment (under- and over- nutrition) a problem in HIV-infected individuals in the United States?

Interactions between Nutritional Status, HIV/AIDS, ART, Comorbidities, and Other Factors:

What is the impact of nutritional status (including under-nutrition and obesity) and nutritional supplements on HIV transmission; acquisition; disease progression; ARV drug absorption, pharmacology, metabolism, and toxicity (including metabolic toxicities); treatment adherence; treatment response; and treatment failure?
What are the interactions among malnutrition, HIV, and ART on non-AIDS outcomes?
What are the interactive effects of coinfections, comorbidities, malnutrition, and illegal drug use on immune function and progression of HIV infection and coinfections?
What is the relationship between early mortality after initiation of ART and nutritional risk factors?

Priorities for Adolescent and Pediatric Populations

Dr. Hazra stated that most or all of the research questions presented by Dr. Fox for adult populations also are applicable to adolescent and pediatric populations. He stated that the impact of nutritional status and nutritional supplements on HIV progression and ARV efficacy, toxicity, and pharmacokinetics are particularly important in pediatric populations. He also noted the importance of questions on over-nutrition in HIV-infected children and adolescents.

Dr. Hazra stated that in settings where replacement feeding of newborns is not acceptable, feasible, affordable, sustainable, and safe (AFASS), the WHO recommends exclusive breastfeeding until six months of age followed by abrupt weaning. He noted the difficulty caregivers have in following this recommendation. He also noted the high priority for research to identify ways to promote exclusive breastfeeding and to educate and counsel mothers and other caregivers on this issue; identify ways to make exclusive breastfeeding safer; determine the optimal duration of breastfeeding; develop parental strategies for handling the challenges of abrupt weaning; and identify feeding, behavioral, and parenting practices that minimize HIV transmission after early weaning.

Dr. Hazra stated that the Working Groups also identified the following priority research questions for the study of nutrition and HIV/AIDS in pediatric populations:

Maternal, Infant, and Child Health

How do perinatal and postnatal strategies to prevent mother-to-child transmission (PMTCT) of HIV affect survival, neurodevelopmental, and neurocognitive outcomes of the child?
How do perinatal and postnatal PMTCT interventions impact the health of the mother? The importance of considering maternal outcomes when assessing the safety and efficacy of these interventions was emphasized.
What strategies are needed to optimally disseminate evidenced-based nutritional interventions, such as education and counseling interventions for mothers and other caregivers, including male partners?
How many HIV-infected women living in the United States or in other settings where AFASS criteria are met choose to breastfeed their children? What factors contribute to this practice? In the United States, are there stigmas associated with not breastfeeding, and if so, in which populations?
Do pregnant HIV-infected teenagers have special nutritional requirements? How does nutritional status affect developmental, behavioral, and physiologic outcomes in mothers and their children in this population?
What are the barriers to adequate nutrition in HIV-infected orphans and vulnerable children?
How common is premastication by HIV-infected individuals of food fed to children? What risk factors are associated with the practice?
How does food insecurity impact risk-taking behaviors and HIV transmission?

Treatment of HIV and HIV-Associated Comorbidities

Can nutrition therapy delay the need to start ART in children older than 1 or 2 years of age whose only criteria for ART is the presence of moderate or severe malnutrition? Dr. Hazra noted the relevance of this question in view of treatment adherence issues, the lifelong nature of ART once initiated, and the risk of long term treatment-associated toxicities in children.
What are the causes of metabolic and developmental sequelae (e.g., high rates of hyperlipidemia, insulin resistance, and glucose intolerance; low bone mineral density; and issues related to pubertal development) in non-obese adolescents who were perinatally infected with HIV and treated with ART from a young age? Dr. Hazra stated that there is a stable cohort of approximately 8,000 to 10,000 perinatally-infected children in the United States who are now entering adolescence and young adulthood. For these individuals, these concerns are particularly relevant.
How can the metabolic and developmental sequelae of HIV-infected adolescents and young adults be managed to minimize long-term morbidity and mortality over a normal life span?
How can the metabolic and developmental sequelae be prevented in children who are perinatally infected with HIV?
Would better TB diagnostics improve treatment of severe malnutrition in HIV-infected children?

Priorities for Contextual Issues and Comorbidities

Dr. Brouwers noted that many of the priority questions previously discussed by Drs. Fox and Hazra include a focus on contextual issues and comorbidities.

Dr. Brouwers noted the consensus of the Working Groups on the need for implementation research in the area of nutrition and the clinical management of HIV/AIDS. He commented on the importance of behavioral studies in implementation research. Dr. Bowers stated that the Working Groups also identified the following priority research questions related to:

Contextual Issues and Comorbidities of HIV-Infected Individuals

What are the barriers (e.g., food texture, appearance, preference, and taste and social stigmatization) to the use of nutritional supplements by HIV-infected individuals? How can nutritional recommendations make optimal use of local food preferences and beliefs?
Does the stigma of being identified as HIV-infected affect an individual’s participation in nutritional supplementation programs?
What behavioral and educational interventions improve the knowledge and knowledge-transfer of attitudes and beliefs about nutrition at the individual, healthcare provider, organizational, and governmental level? Dr. Brouwers noted the need for local healthcare providers to understand the importance of nutrition in the care of HIV-infected individuals.
What are the differences in the objectives of an approach to nutrition in a clinical setting versus a public health approach to nutrition?
How can local food sources be incorporated into nutritional supplement programs to avoid the creation of a dependency on food not available locally? Dr. Brouwers stated that the development of sustainable interventions will require community participation in defining the research setting and agenda.
How can nutrition therapy be integrated into the clinical management of HIV disease at clinics in different settings and populations?
What economic factors influence an individual’s decision to purchase medication, food and nutrition, and/or drugs of abuse or alcohol in resource-poor settings?
What parental techniques are most helpful for comforting a child after early weaning?
What family and community supports reduce the stigma associated with HIV infection and with not breastfeeding?
What are the long term social and emotional consequences of not breastfeeding to the mother and the child? Dr. Brouwers noted the role of breastfeeding in the bonding between mother and child.
What interventions promote sustained lifestyle and behavioral changes that improve the nutritional status of HIV-infected individuals and also reduce the morbidity associated with the interaction of HIV disease, ART, and malnutrition? Dr. Brouwers cited the example of encouraging compliance with WHO recommendations for the feeding of infants of HIV-infected mothers.
How can role model and social network approaches be used to this effect? Dr. Brouwers emphasized the need to include special populations, such as the elderly, adolescents, and people who use drugs of abuse, in this research.
What are the social harms and stigmas, as well as beliefs and perceived norms, related to food, nutrition, and HIV/AIDS in affected communities? Would the perceived harms, stigmas, beliefs, and/or norms lead to biased reporting on surveys and questionnaires?
What are the critical secondary behavioral outcomes (quality of life, return to work, etc.) that may impact the effectiveness of nutritional interventions?
What are the neurocognitive and behavioral outcomes of HIV disease and malnutrition, particularly in childhood and adolescence?
What are the effects of malnutrition (under-nutrition and obesity) and food insecurity on the socioeconomic and behavioral risk factors for acquisition of HIV?
How do traditional, complementary, and alternative therapies affect nutrition and its effects on HIV disease and ART?

Ethics of Research on Nutrition and HIV/AIDS

What are the ethical considerations for:

Observational studies that may include individuals with nutritional abnormalities or deficiencies?
Studies that provide nutritional supplements to some or all HIV-infected individuals, but not to individuals with other diseases or the entire community in a food insecure population?
Provision of nutritional supplements provided during a clinical trial after the trial has ended? How is this issue understood by Institutional Review Boards (IRBs) or Institutional Ethics Committees (IECs), investigators, and local institutions?
Nutritional interventions that may benefit either the mother or the child, but not both?

Utilization of Research Resources

Should nutritional interventions and nutrition research be targeted to the level of the individual, the family, and/or the community for maximum effectiveness, particularly in farming communities?
How can nutrition issues be integrated into existing AIDS clinical trials?
Can a step wedge design clinical trial of nutrition and HIV/AIDS interventions be used effectively in partnership with other organizations, such as the United States President’s Emergency Plan for AIDS Relief (PEPFAR) or international development assistance organizations?
How can existing databases and other resources be used to address nutrition and AIDS research?
How should data on food preferences in local communities be collected? Would ethnographic studies be appropriate?
Can a standardized universal instrument that is adaptable to cultural and local norms be developed to measure body mass, body composition, and dietary variables in settings of limited resources and high patient volume?

Acknowledgements

Dr. Whitescarver thanked the Rapporteurs for their summaries of the Working Group sessions. Drs. Raiten and Sato expressed their gratitude to all of the individuals involved in the organization of the Workshop. They commented on OAR’s past support for the development of WHO guidelines on nutrition and the urgent need to convene a state-of the-science symposium that will guide the development of a research agenda on nutrition and the clinical management of HIV/AIDS.

Discussion

OARAC members discussed the importance of research on nutrition and the clinical management of HIV/AIDS. Dr. Curran also encouraged Workshop attendees and NIH staff to participate in the discussion.

The topics discussed included the need to integrate current knowledge on nutrition into evidence-based guidelines for the treatment and prevention of HIV/AIDS; the opportunity to leverage existing research resources for nutrition and AIDS research; and support for novel clinical trials, interdisciplinary research, and studies in special populations in the United States and internationally. The urgent need for standardized measures of nutritional status was noted several times during the discussion period.

The importance of incorporating nutrition into the care of HIV-infected individuals was discussed. Several participants questioned whether sufficient information is currently available to develop evidence-based recommendations. It was noted that the New York State Department of Health AIDS Institute HIV treatment guidelines include a section on nutrition. The WHO pediatric HIV treatment guidelines also include a section on nutrition. It also was noted that one of the supplements to the Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection includes information on nutrition, hyperlipidemia, and osteopenia. Participants commented on the importance of incorporating measures of basic nutritional status into ongoing AIDS research, including prevention studies, to inform the development of evidence-based guidelines.

OARAC members and meeting participants discussed the need for additional research on the interaction of nutrition and the clinical management of HIV/AIDS. It was noted that some investigators interested in integrating nutritional research into ongoing clinical studies have had difficulty obtaining funding from NIH for these studies. OARAC members also emphasized the need to bring new researchers, including those from other disciplines, into this field.

Public Comments

No members of the public requested time to comment.

Conclusions

Dr. Curran stated that interdisciplinary research on nutrition and HIV/AIDS and on the development of standardized measures for the assessment of nutritional status, particularly in resource limited settings, are high priority areas of research. He noted the importance of attracting new investigators to nutrition and AIDS research. He stated that the exercise of developing national and international guidelines on nutrition and the clinical management of HIV/AIDS using existing knowledge may help to further identify areas where research is needed.

Dr. Whitescarver thanked the OARAC members and guests for their participation in the Workshop on Nutrition and HIV/AIDS and in the Council meeting. Dr. Whitescarver noted that the trans-NIH strategic plan for HIV-related research includes issues related to nutrition. He encouraged researchers to submit requests for grant supplements for studies of nutrition and HIV/AIDS, particularly if Congress provides NIH with a funding increase for FY 2009. He noted that OAR will consider the research priorities identified at the Workshop on Nutrition and HIV/AIDS and discussed at the Council meeting when developing the FY 2010 trans-NIH AIDS research budget request.

The meeting adjourned at 4:00 p.m. on October 24, 2008.

Signed:

/Jack Whitescarver, Ph.D./
Jack Whitescarver, Ph.D., Executive Secretary

/James W. Curran, M.D., M.P.H./
James W. Curran, M.D., M.P.H., Chair

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