Meeting Minutes - November 14, 2013

Office of AIDS Research Advisory Council
Thirty-sixth Meeting
November 14, 2013

National Institutes of Health
U.S. Department of Health and Human Services
5635 Fishers Lane Conference Center
Rockville, MD

Members Present: Dr. Sharon Hillier (Chair), Dr. Jack Whitescarver (Executive Secretary), Dr. Stefano M. Bertozzi, Dr. Myron S. Cohen, Dr. Steven Deeks, Dr. Clemente Diaz,* Dr. Igor Grant, Dr. Roy Gulick,* Dr. David Malebranche, Dr. Rochelle P. Walensky, Mr. Mitchell J. Warren, Dr. Darrell P. Wheeler, Dr. Craig M. Wilson

*Membership pending clearance

Ex Officio Members Present: Dr. Francis Collins, NIH Director; Dr. James Anderson, Director, NIH Division of Program Coordination, Planning, and Strategic Initiatives; Dr. John Bartlett, Working Group on Clinical Practice for the Treatment of HIV Infection; Dr. Carl W. Dieffenbach, Director, NIAID Division of AIDS; Dr. Martin Hirsch, Working Group on Clinical Practice for the Treatment of HIV Infection

Invited Speakers and Guests: Mr. Moisés Agosto-Rosario, Dr. Judith D. Auerbach, Ms. Dawn Averitt Bridge, Dr. Charles C. J. Carpenter, Dr. James W. Curran, Dr. Ralph J. DiClemente, Dr. Barton F. Haynes, Dr. King K. Holmes, Dr. Kevin P. High, Dr. Priscilla Hsue, Dr. Henry Masur, Dr. Ronald T. Mitsuyasu, Dr. Michael S. Saag, Dr. Paul A. Volberding

Welcome and Meeting Overview

The National Institutes of Health Office of AIDS Research Advisory Council (OARAC) convened its thirty-seventh meeting on April 11, 2013 at 8: 30 a.m. at the Fishers Lane Conference Center in Rockville, Maryland.

OARAC Chair Sharon L. Hillier, Ph.D., Professor of Microbiology and Obstetrics and Gynecology, and the Director of the Magee Women’s Research Institute, University of Pittsburgh, welcomed Council members, invited speakers, and guests and reminded everyone that this and future OARAC meetings will be videocast live. The minutes of the April 11, 2013 OARAC meeting were approved as written.

CONFLICT OF INTEREST STATEMENTS

OARAC members were reminded to review and sign their conflict-of-interest forms and to submit them to Office staff.

UPDATE ON OARAC WORKING GROUPS FOR TREATMENT AND PREVENTION GUIDELINES

Pediatric Guidelines for Opportunistic Infections (OIs)

Dr. Lynne Mofenson, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development provided an update on the pediatric OI guidelines including their publication in AIDSinfo, an updated format, and the addition of new sections.

The Pediatric Guidelines have been published as a supplement in the Pediatric Infectious Disease Journal, and an executive summary has been published in this journal and in the Journal of Pediatric Infectious Disease Society. Dr. George Siberry will assume responsibility as executive secretary for these guidelines.

Guidelines for the Use of Antiretroviral Agents (ARV) in Pediatric HIV Infection

The Pediatric ARV Treatment Guidelines have been revised and are expected to be released in December 2013. Revision of the perinatal guidelines is under way and is anticipated to be released in early 2014.

Four new scientific members, two new community members, and one new government member have joined the perinatal guidelines panel. The panel also has a new representative for the Perinatal Hotline.

Adult Guidelines-Opportunistic Infections

Dr. Henry Masur of the NIH Clinical Center reminded OARAC that the adult OI guidelines are a collaboration among NIH, the Centers for Disease Control and Prevention (CDC), and the Infectious Diseases Society of America (IDSA).  He reported that an online version of the guidelines was established in May 2013, and the revision process allowed for real time updates of changes in the online version. There are a variety of revisions under way. These guidelines are used regularly and receive several thousand downloads and page views each month.

Guidelines on Antiretroviral Therapy in Adults and Adolescents

Dr. John Bartlett, Professor Emeritus at Johns Hopkins University, ex officio OARAC member, and founder and Chair of the HIV Guidelines Committee reported that the Guidelines on Antiretroviral Therapy in Adults and Adolescents were last updated in February 2013. A major revision of the guidelines and the selection of new members is underway.  The panel has been invited to publish a succinct form in the Annals of Internal Medicine. The panel is close to reaching its goal of less than 50% of members with conflicts of interest, and the panel Co-Chairs have none.

Dr. Bartlett announced that he is retiring as Co-Chair of the Panel on Antiretroviral Guidelines for Adults and Adolescents. Drs. Roy Gulick and Martin Hirsch will serve as non-government Co-Chairs for the panel, while Dr. Cliff Lane will continue as government Co-Chair.  At the end of his presentation, Dr. Bartlett received a standing ovation for his service on the panel and in the field of HIV/AIDS overall.

DISCUSSION

There was discussion on current infant treatment recommendations and the lack of pharmacokinetic and safety data on neonates. It was noted that the guidelines provide essential information for health care providers to make informed decisions on what is clinically relevant and necessary.

DIRECTOR’S REPORT AND INTRODUCTION TO THE MEETING TOPIC

Dr. Jack Whitescarver, Director of the NIH Office of AIDS Research (OAR), welcomed everyone to this meeting of OARAC. Dr. Whitescarver announced the establishment of a new section within OAR focused on research toward cure, which will be directed by Dr. Paul Sato, who joined OAR as a medical officer. Dr. Sato also will chair the OAR Cure Coordinating Committee, which is comprised of representatives of the Institutes, Centers, and Offices (ICOs) that have research portfolios in this area.

He thanked Dr. Hillier, the outgoing OARAC Chair, for her leadership and presented her with a certificate of appreciation for her services. He welcomed new OARAC members: Drs. Clemente Diaz, David Malebranche, and Darrell Wheeler. He also introduced Mr. Moisés Agosto-Rosario and Drs. Charles Carpenter, James Curran, Ralph DiClemente, and Paul Volberding, who will serve on a working group charged with reviewing ongoing OAR-supported research (see Charge to OARAC).

Dr. Whitescarver recognized Dr. John Bartlett as both a friend and leader not only with respect to the development of the antiretroviral guidelines, but to the HIV/AIDS research community and to OARAC. Dr. Whitescarver presented him with a token of appreciation for his years of service.

He reminded OARAC that the NIH and OAR budgets remain flat, expressing concerns about the future budget, as the estimate for FY2013 reflects the sequester, with roughly a 5% budget reduction for the AIDS portfolio. With budgetary constraints likely to continue into the future, OAR is closely examining the trans-NIH research currently supported by AIDS dollars.

Dr. Hillier introduced today’s tropic, “NIH AIDS Priority-Setting in an Era of Budget Constraint,” as an opportunity to take a broad look at the overall AIDS research portfolio and explore scientific opportunities and research priorities in prevention, comorbidities, disease progression, and cure. She stated that today’s meeting would set the stage for a careful review of the NIH HIV/AIDS research portfolio as requested by the NIH Director, Dr. Francis Collins, to ensure that research currently supported by AIDS dollars align with the highest HIV/AIDS research priorities.

CHARGE TO OARAC

Dr. Francis Collins, NIH Director, remarked that scientific opportunities abound in many fields, noting the remarkable progress in HIV prevention research, such as progress in vaccines, new findings about broadly neutralizing antibodies, and other biomedical prevention, including NIH research that demonstrated risk reduction afforded by male circumcision and test-and-treat protocols. He discussed how budgetary constraints are forcing NIH to closely examine its spending decisions to ensure that resources are appropriately invested to support progress in the highest-priority areas. Dr. Collins asked OARAC, with additional external input, to develop a blueprint to identify the highest research priorities for HIV/AIDS research funding to guide OAR investments over the next 3 to 5 years. (see attached Charge from the NIH Director)

Dr. Collins requested a report on HIV/AIDS research priorities that are bold but achievable; specific enough to guide decision making but avoiding over-granularity; comprehensive in its consideration of the broad sweep of AIDS research but courageous in identifying major priorities. He asked that the report outline the highest priority AIDS research in three areas:

• Prevention – including vaccines, microbicides, ARV-based prevention, behavioral research focused on risk reduction, stigma, and adherence

• Treatment – including advances in therapeutic interventions and research toward a cure

• Co-morbidities – neurologic, cardiovascular, oncologic, accelerated aging

He stated that the document should also identify high priority research in three areas that cut across these themes – basic science, training (including capacity building), and information dissemination.

He asked for a four- to six-page executive summary to serve as a guide, with a draft due in spring, 2014. The draft will receive comment OARAC and from key stakeholders, and a revised document is expected to be presented to the Advisory Council to the Director (ACD) at its June 2014 meeting. Dr. Collins stated that this report could potentially lead to additional OAR oversight functions with a more proactive approach to ensure that AIDS research dollars are supporting the highest priorities. A prospective approach would place NIH in a position to more rigorously defend the way it allocates its AIDS funds.

DISCUSSION

Dr. Collins clarified the potential benefits of the priority setting exercise. The OARAC priority review subcommittee could consider opportunities for collaboration across Federal agencies and identify the highest priorities for HIV/AIDS research opportunities. OAR could be involved at an earlier time in discussions regarding whether a funding opportunity is appropriate for the AIDS budget. In instances where funding opportunities are not solely AIDS-related, co-funding could be considered as an alternative. He recognized this is an opportunity for the OARAC sub-committee to balance boldness and innovation with feasibility. Priorities should be inspiring to the HIV/AIDS research community, but also achievable.

OARAC members suggested that implementation science should be included in the blueprint as a way to translate research successes for community use and achieve NIH’s goal of reducing infections and treating patients who are infected.

AIDS VACCINE RESEARCH

Dr. Barton Haynes, Director of the Duke Human Vaccine Institute at Duke University, discussed current progress in vaccine research, including the use of T-cell immunogens to control HIV.

He also discussed the RV144 clinical trial that evaluated the efficacy of a prime boost immunization strategy. The investigators on this trial have observed a vaccine efficacy rate of 31.2% and found that higher binding between immunoglobulin G (IgG) and the presence of V1V2 recombinant fusion protein correlates with a lower infection rate. The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) is collaborating with industry and the Bill and Melinda Gates Foundation on an HIV Vaccine Trials Network (HVTN) phase I follow-up trial in high-risk populations in South Africa. Dr. Haynes also discussed broadly neutralizing antibodies, noting that more than 120 antibodies that bind to the four sites identified as the “Achilles heels” have been isolated, but that attempts to induce them have been unsuccessful,

The Duke CHAVI-ID and other groups are designing vaccines based on B-cell lineages, with the goal of favoring broadly neutralizing lineages, shorter lineages with fewer mutations, lineages with little to no autoreactivity, and normally subdominant lineages. Dr. Haynes outlined current and future vaccine strategies that are priorities. These include:

• Animal models for vaccine strategies and testing that are under investigation although progress has been hampered by the lack of a native trimer

• Vaccine design that will involve a combination of the correct high-affinity immunogens and the correct structure.

Dr. Haynes closed his presentation by anticipating future progress in understanding how to generate protective T-cell and antibody responses to HIV. He anticipated that the tempo of studies in both non-human primates and humans will accelerate and provide the immunogenicity information needed to design efficacy trials. He also pointed out that several NIH-funded groups in the HIV/AIDS vaccine field are working together to exploit synergies and ensure continued progress.

AIDS-RELATED MALIGNANCIES

Dr. Ronald Mitsuyasu, Director of the University of California, Los Angeles, Center for Clinical AIDS Research and Education, noted that malignancies have been part of the AIDS epidemic from the very beginning. Although the evolution of the epidemic has resulted in a decline in many AIDS-defining illnesses, malignancies still constitute a large part of the international AIDS epidemic. He noted that including non-AIDS defining cancers (NADC), cancer-related deaths account for more than a third of deaths among all HIV-infected patients and the impact of HIV on cancer behavior, immune control, and disease-free survival is unclear.

Dr. Mitsuyasu emphasized that cancer is a growing problem in HIV/AIDS and requires further study. He highlighted recommendations by the National Cancer Institute (NCI) Board of Scientific Advisors Subcommittee on HIV and AIDS Malignancy, which was convened by Dr. Harold Varmus, NCI Director, and the NCI Office of HIV and AIDS Malignancy (OHAM) to identify and prioritize major questions in this field.

This subcommittee recommended:

• A focus on the seven HIV-associated cancers

• Capacity-building and research in resource-limited regions

• The study of HIV tumors for insights into cancer pathobiology

The NCI subcommittee also expressed enthusiasm for the Provocative Questions initiative on AIDS malignancies, a large randomized trial evaluating whether treatment of high-grade anal intraepithelial neoplasia can prevent anal cancer, and more epidemiologic studies on AIDS and malignancies, particularly in resource-limited regions. The subcommittee also suggested an increase in efforts to improve data collection and genotyping for HIV-associated cancers and NADC. It was also noted that expertise within the NCI and the cancer centers it supports can aid in efforts to conduct research towards a cure for HIV infection.

Dr. Mitsuyasu then highlighted specific subcommittee recommendations for each of the seven notable cancers seen with HIV. He also noted the need for infrastructure, increased capacity, and improved diagnostic pathology in resource-limited regions and increased collection of information on cancers in HIV-infected children.

He also highlighted research areas that could contribute to a general understanding of cancer, including:

• Molecular characterization of HIV-associated tumors

• Effects of premature aging on cancer development

• Novel infectious agents that contribute to pathogenesis

• The tumor microenvironment in HIV-infected patients

• Changes in tumor incidence among HIV-infected individuals

Additional areas of interest include pharmacokinetic interactions between cancer drugs and ART, the role of frailty and polypharmacy in cancer drug toxicity, and screening and treatment for multiple morbidities.

NEURO-AIDS

Dr. Igor Grant, Director of the HIV Neurobehavioral Research Program at the University of California, San Diego, reminded the Council that the April 2013 OARAC meeting focused on HIV-associated neurocognitive disorders (HAND). The neuropathogenic mechanisms underlying HAND remain poorly understood. Additional information is needed about dendritic simplification, which might play a role in HAND, toxic products of the virus, such as Tat, which persist in the cerebrospinal fluid (CSF) despite evidence that viral replication is controlled in the plasma, and the development of reliable biomarkers for HAND.

Ongoing studies on the relationship between HAND and immune status and virologic suppression offer some clues about potential areas of focus. Pharmacokinetics of ARVs differ between CSF and plasma and are affected by age. Studies about neuroprotection and neuroremediation may inform the assessment and management of HAND.

Dr. Grant concluded his presentation by reporting on a review by the Neuro-AIDS working group previously commissioned by OAR.

On the basis of its review, the working group prioritized research on:

• HIV reservoirs in the CNS

• Neuropathophysiology

• Etiology of cerebrovascular disease

• The potential continued effects of viral products

• Development of biomarkers

• Development of CNS-specific therapeutics

• Clinical studies, particularly on acute and early infection

Dr. Grant emphasized the importance of a research strategy that includes traditional support mechanisms and longitudinal studies focused specifically on neuro-AIDS. This includes the recruitment and maintenance of study populations with neurological complications, rather than attempting to add complex neurological studies to ongoing population studies. Mental health outcomes in HIV-exposed but uninfected infants was noted as another topic of interest.

DISCUSSION

It was noted in the discussion that encouraging researchers from other disciplines to focus on HIV/AIDS had produced positive results. Not only has this increased the number of HIV-related areas under investigation, but it has also led to new research questions that have implications beyond HIV. Dr. Grant emphasized the importance of clinical and longitudinal studies to facilitate new hypotheses and basic research. He called for the neurological symptoms to be examined as an integral part of HIV disease rather than as a separate comorbidity. There was also discussion about the effects of improved testing, treatment, and care on the prevalence of neuro-AIDS and AIDS-associated malignancies.

HIV-ASSOCIATED CARDIOVASCULAR COMPLICATIONS

Dr. Priscilla Hsue, Associate Professor of Medicine at the University of California, San Francisco, noted that rates of cardiovascular disease (CVD), myocardial infarctions (MI), cardiac-related hospitalizations, and MI-associated mortality are higher in HIV-infected patients, including those who are effectively treated. HIV infection is as strong a risk factor for cardiovascular disease as traditional factors such as diabetes, smoking, and older age. Treatment with ART may also increase CVD in HIV. Most studies are not statistically powered to examine CVD outcomes in HIV-infected patients.

Dr. Hsue outlined several unanswered questions in the field of HIV and CVD, including:

• What is the value of extrapolating existing knowledge about CVD treatment to the HIV-infected population?

• Should HIV receive the same consideration as other diseases such as diabetes in CVD risk factor management?

• What is the impact of treated HIV infection on immunologic and inflammatory factors that are potentially associated with CVD, and do these factors predict premature CVD

• What are the best biomarkers, safety issues associated with novel HIV agents, and potential lessons from other inflammatory conditions that also should be explored?

Dr. Hsue pointed out that the HIV-infected population is well studied and engaged and that studies in this population could inform HIV care, and mechanisms, therapeutic targets, and optimal treatments for other comorbidities in HIV-infected patients. Studies in CVD could also inform other HIV-related issues, including efforts in research toward a cure.

HIV-ASSOCIATED CO-INFECTIONS

Dr. Henry Masur, Director of the NIH Clinical Center, noted successes in the developed world in addressing opportunistic infections (OIs) and emphasized the need to continue funding research in these areas. Although data from the HIV Outpatient Study indicate that many of these OIs are declining, there still remain substantial numbers of new HIV cases diagnosed each year, and many patients still do not receive treatment early enough in their infection. Dr. Masur noted that continued interest in the adult OI guidelines reflects that OIs present a continuing problem. He also noted that research support still is needed to:

• Maintain surveillance, operationalize and scale up advances, and understand how to use information garnered by new molecular diagnostic tests

• Understand coinfections such as HIV-related TB, including TB transmission, the effect of HIV on TB latency and retransmission, how to reduce risk, and critical research questions in surveillance, diagnosis, prevention, and therapeutics

• Tackle TB globally to have an impact on HIV-associated morbidity and mortality

• Expand expertise in hepatitis C (HCV) or B (HBV), as well as human papillomavirus (HPV).CDC data show for the first time that HCV coinfection is causing more deaths in the United States than HIV directly, and long-term consequences of HIV infectionare accelerated by HCV coinfection

Research areas include:  

• Behavioral and biological aspects of Hepatitis reinfection

• Optimal regimens for specific subpopulations

• Management of early and late fibrosis, viral and host issues related to prognosis and response to therapy, polymorphisms that might lead to resistance, and further study of the use of new curative regimens to eradicate HCV

• Development of simpler regimens to facilitate HCV treatment adherence

• Continued research on  traditional OIs, as well as sexually transmitted infections (STIs) such as gonorrhea, chlamydia, and syphilis

Dr. Masur called for expanded expertise in hepatitis C (HCV) or B (HBV), as well as human papillomavirus (HPV) and maintained or expanded expertise in the study of OIs. He noted the potential for re-emergence of OIs that seem to have disappeared and the need to maintain knowledge to address them.

HIV AND AGING

Dr. Kevin High, Professor of Medicine and Translational Science, Chief of the Section on Infectious Diseases, and Interim Chair of the Department of Internal Medicine at the Wake Forest School of Medicine, cited research on HIV and aging as an area with the potential to generate the biggest return on investment. He noted that there are an increasing number of people older than 50 years who are infected with HIV. Age is a risk factor in many emerging HIV-associated comorbidities, and the prevalence of multi-morbidity is higher among HIV-infected individuals. Age-associated factors such as frailty before HAART initiation may have implications for survival. Aging appears to be accelerated in HIV infection. HIV accentuates aging in multiple organs, resulting in accumulated deficits and a lack of physiologic reserve at younger ages than is seen in HIV-negative individuals.

Dr. High reported that a working group on HIV and aging organized by OAR produced a research roadmap focused on:

• The mechanisms and triggers of functional decline in HIV-infected individuals

• Biomarkers and clinical indices

• Aging with HIV, multi-morbidities, and clinical care

• Societal infrastructure, mental health and substance abuse, and caregiver issues

Dr. High also described efforts to support collaboration and leverage resources between the National Institute on Aging (NIA)-supported Older American Independent Centers (OAICs, “Pepper Centers”) and NIAID-supported Centers for AIDS Research (CFARs) on HIV/aging and aging research. Dr. High concluded his presentation by noting the critical need for increased study section expertise, comfort with complexity in HIV and aging research, and the analysis of research outcomes other than survival in this population.

DISCUSSION

The discussion addressed:

• the importance of including HIV-infected patients in the CVD trials to better understand the relationship between HIV, HIV treatment, and CVD;

• the benefits of research on HIV and aging on other chronic diseases where aging appears to be accelerated;

• the importance of behavioral and social science questions, such as neuropsychological mechanisms underlying risk behaviors among younger individuals;

• structural issues that affect access and health care utilization; and

• the importance of maintaining existing cohorts that can facilitate critical harmonization and standardization of data collection.

RESEARCH TOWARD A CURE

Dr. Steven Deeks, Professor of Medicine at the University of California, San Francisco, noted the obvious reasons for seeking a cure. He pointed out that the burden of disease among HIV-infected patients on treatment arises from many factors, including treatment toxicity and poly-pharmacy; and treatment does not reverse HIV-associated disease. In addition, the delivery of therapy to millions of people worldwide is logistically challenging. Dr. Deeks noted several challenges to achieving HIV cure including the poorly defined mechanisms for HIV persistence, lack of understanding viral reservoirs, continued HIV replication in lymphoid tissues, and the inability of the host to clear HIV. He noted the need for:

• The identification ofa biomarker that can be used scientifically and clinically to document viral replication

• The development of a scalable, affordable cure  

• Better non-human primate models to study viral reservoirs and cure

Dr. Deeks described the NIH Martin Delaney Collaboratories, an investment of $70 million over 5 years. Among their efforts, the collaboratories are examining ways to modify stem cells and T cells with gene therapy, studying eradication by screening Merck activating agents for molecules that reverse latency, and examining host-virus interactions.

There is concern about overly high expectations for these collaboratories and limitations on their capacity to address all major questions. He noted that additional collaboratories focusing on cure research are being formed worldwide. Industry, regulators, NIH, foundations, and academia can form public-partnerships to develop new research approaches to address barriers.

MICROBICIDES RESEARCH

Dr. Hillier noted that microbicides research, which is still a young field, aims to address unmet needs in prevention. In the United States, the rate of new infections arising from heterosexual contact and injection drug use has remained relatively flat, but approximately 50,000 new infections occur each year among men having sex with men (MSM). In addition, receptive sexual partners are more vulnerable to HIV infection, but less likely to control condom use. Microbicides, which deliver HIV prevention products topically to the sites of infection, have the potential to be a cost-effective method to control HIV. In South and Sub-Saharan Africa, the incidence of HIV infection remains high among young, unmarried women, despite nationwide rollouts of treatment programs.

Dr. Hillier discussed the need for rectal microbicides, noting that unprotected, receptive anal intercourse is the highest-risk sexual activity for HIV transmission and is practiced among men and women in the developed and developing world.She also discussed the need for vaginal microbicide gels to reduce infection rates among women. She reported that surrogates of efficacy have been developed including PK measurements in vaginal and rectal tissue that demonstrate that topical application of ARVs result inhigher levels than oral ARVs. New drug combinations, better applicators, tablets and suppositories, and other user-friendly products are under development.

A better understanding of adherence issues in microbicide clinical trials is critical. Post-trial data indicated that many participants misrepresented their adherence behavior.Participants reported that gels were messy and indiscreet and that antiretroviral use was stigmatized. Investigators are considering other ways to deliver microbicide products in ways that can fit a variety of women’s lives.

Highlighted research priorities for microbicides:

• The formation of cross-sector partnerships

• The development of products that people will use, including a potential vaginal ring that delivers continuous low-dose antiretrovirals to the vagina and cervix,

• Studies that address the impact of hormonal contraception on women’s HIV risk andmucosal safety

• The impact of topical microbicides on HIV resistance

• Bridging studies on microbicide safety for adolescent, pregnant, breast-feeding, and mature women

• Social science studies to determine who will use microbicide products.

BEHAVIORAL AND SOCIAL SCIENCE RESEARCH

Dr. Judith Auerbach, Adjunct Professor in the Center for AIDS Prevention Studies at the University of California, San Francisco School of Medicine, pointed out that behavioral and social science issues are fundamental to every topic discussed during this meeting including:

• Understanding characteristics that contribute to differential risk
• Methods to reach, recruit, and retain highly stigmatized populations for screening, prevention, treatment, and research
• Opportunities and strategies to maximize population-level effects of interventions
• The most effective combinations of interventions
• Health disparities and inequalities

It is important to explore the experience of individuals in the context of interpersonal relationships, social institutions, and cultural and environmental contexts, particularly as they relate to risk factors such as sexual activity and drug use.

A recent review group was convened by the OAR to examine the behavioral and social science research portfolio and identify priorities and opportunities.

Their priorities included research on:

• Basic behavioral and social science including further development of models and methods to study the interpersonal and social mechanisms underlying the complexity of ways HIV is acquired and transmitted

• Social, structural, and policy factors and interventions exploring how environmental factors such as politics, economics, violence, and health services delivery affect vulnerability or resistance to HIV infection

• Factors affecting engagement in preventive care and the HIV care continuum

• The use of innovative methods such as social media and adaptive intervention design

• Implementation science and optimization of proven interventions

• Comorbidities and syndemics

• Social and behavioral research combined with biomedical technologies focused on recruitment and retention in clinical trials and the inclusion of behavioral and social sciences research in the development and implementation of biomedical technologies independent of trials.

Dr. Auerbach noted that the inclusion of social and behavioral sciences in biomedical research has particular implications for adherence, which is the behavioral bridge between efficacy and effectiveness.

AIDS THERAPEUTIC RESEARCH

Dr. Michael Saag, Professor in the Department of Medicine and the Jim Straley Chair in AIDS Research at the University of Alabama, Birmingham, discussed the successes of HIV therapeutics research including the achievement of an undetectable viral load through HIV treatment. Dr. Saag delineated important priorities for HIV therapeutics research, including:

• Implementation science (IS) to optimize effective treatment approaches and answer specific research questions centered on testing and engagement in care, long-term outcomes, and costs.

• Research to determine when to start therapy, a continuing point of debate, despite increasing evidence that argues for starting early

• Studies to determine how to minimize  adverse effects associated with long-term HIV therapy

• Understanding cross-cutting issues such as aging and inflammation that might be common pathways underlying the adverse effects related to treatment

• Understanding comorbid conditions and their potential impact on when to start therapy and what kinds of therapeutics to use

• Research on coinfections to inform rational decisions about which therapeutics to use and how to achieve the best outcome

• The impact of substance use and mental health on adherence and engagement with care

• Research on factors involved in a potential HIV cure

• Development of new antiretroviral drugs

• The use of therapeutics in special population such as children and adolescents.

Dr. Saag concluded by emphasizing that demonstrating efficacy is only a start; therapeutics research also must show how these interventions could fare in the real world.

DISCUSSION

OARAC members and speakers endorsed the key areas of research presented and highlighted important considerations for setting priorities.They noted the need to spend efficiently, while recognizing that clinical trials, which can be costly, are necessary to achieve success. Emphasis was placed on the need for interdisciplinary and multidisciplinary teams to move the AIDS research field forward.

Other priorities noted include:

• The need for Implementation science to improve uptake of successful interventions. There was discussion of how to organize the principles and overall goals of IS research, and appropriate role for NIH in this field.  It was suggested that NIH form partnerships with groups that have the appropriate expertise

• Community participatory research which has resulted in many successes in prevention. . It was recommended the communities should be involved early in the process of developing interventions.

• Behavioral and social sciences research. It was noted that there is difficulty garnering support for such research. There is skepticism regarding the ability to change behavior and society, as well as stigma and shame associated with HIV and HIV risk behaviors.  In addition, non – behavioral or social sciences researchers assume they know how to conduct behavioral and social science research which limits the ability to carry out this research effectively. Social science is fundamentally about social change and traditional research methods, such as randomized clinical trials, may not be applicable in these fields

• Empirical research that can be facilitated by large amounts of available data. Existing funding mechanisms and academic culture emphasize hypothesis-driven research and devalue empirical, hypothesis-generating work

• Prevention research, including vaccines and other prevention strategies to match the success of treatment research.

• Other priorities that had not been discussed in depth at this meeting:

  • PrEP

  • Cost effectiveness research

  • Social factors such as education, unemployment, and the criminal justice system

  • Research training. In particular, the group noted that an entire generation of researchers will be lost because of current budgetary constraints

  • The loss of potential researchers from underrepresented groups

PUBLIC COMMENTS

No members of the public requested time to comment.

CLOSING COMMENTS

Dr. Whitescarver thanked all speakers for taking the time to provide cogent and important comments to OARAC. He reiterated that this meeting was intended to consider where the greatest opportunities and priorities lie in AIDS research.  He emphasized that the purpose of the priority setting project is to ensure that the highest-priority areas are preserved. OARAC members were asked to submit additional comments on their views of the highest priorities to OAR. A draft blueprint will be provided for OARAC to review. Dr. Whitescarver also noted that the OARAC priority setting working group would convene on November 15, 2013 to begin reviewing the existing AIDS research portfolio, and that the priorities discussed at this OARAC meeting will be critical to their portfolio analysis.

ADJORN

The meeting was adjourned at 5:00 p.m. on November 14, 2013.

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

/ Sharon L. Hillier, Ph.D./
Sharon L. Hillier, Ph.D., Chair