NIAID Council Minutes: September 12, 2016

The 184^th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:30 a.m. on Monday, September 12, 2016, in Conference Rooms E1/E2, Building 45, National Institutes of Health. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.

In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:45 a.m. and from 1:00 p.m. to 3:05 p.m. The meeting was closed to the public from 8:30 a.m. to 10:15 a.m. and from 11:45 a.m. to 12:00 noon for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Table of Contents

I. Review of Grant Applications
II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
III. Guest Speaker—Steven Holland, M.D., director, Division of Intramural Research, NIAID
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT
V. Report of the Microbiology and Infectious Diseases Subcommittee–Irene Glowinski, Ph.D., acting director, DMID
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS
VII. Adjournment

I. Review of Grant Applications

The National Advisory Allergy and Infectious Diseases Council convened in closed session to consider applications in allergy and immunology, microbiology and infectious diseases, and AIDS.

Funding Actions: The Council reviewed 5,046 research and training applications with primary assignment to NIAID for a requested amount of $2,048,271,785 in first-year direct costs and recommended approval of 2,295 applications with $791,947,788 in first-year direct costs.

II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.

Dr. Fauci opened the Council session by welcoming visitors to the meeting. He introduced two ad hoc Council members, Dr. Allan Kirk, chair of the Department of Surgery, Duke, and Dr. Joren Madsen, professor of surgery at Harvard and director of the Transplant Center at Massachusetts General Hospital.

Council member Ms. Maria Acebal was unable to attend the meeting.

Dr. Fauci acknowledged the contributions of four retiring Council members—Ms. Maria Acebal and Drs. Norman Baylor, Robert Belshe, and Diane Griffin—and presented them with plaques and certificates of appreciation for their service.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the June 6, 2016 meeting and approved them as written.

Staff and Organizational Changes

NIH Director Dr. Francis Collins announced that Dr. Diana Bianchi has been selected as the new director of the National Institute of Child Health and Human Development (NICHD). She will replace Dr. Catherine Spong who has served as acting director of NICHD.

Dr. Joshua Gordon has been named director of the National Institute of Mental Health. He replaces Dr. Bruce Cuthbert who served as acting director after the departure of Dr. Tom Insel.

In June, Dr. Fauci appointed Dr. Steve Holland as the new director of the Division of Intramural Research, NIAID. Dr. Holland has served as the chief of the Laboratory of Clinical Infectious Diseases since 2004 and as NIH deputy director for intramural clinical research since 2011.

Dr. Jill Harper has been selected as the director of the Office of Biodefense Research and Surety. Dr. Harper will also continue to serve as NIAID associate director for science management and deputy executive officer.

Dr. Fauci announced two new additions to the NIAID Office of the Director. Dr. Bob Eisinger is special assistant for scientific projects, and Dr. Catharine Paules is a clinical associate.

Dr. Ruth Ebiasah is the new chief of the Pharmaceutical Affairs Research Branch in the Office of Clinical Site Oversight, Division of AIDS.

Tributes and Awards

Dr. Fauci paid tribute to Dr. Hillery Harvey, associate director of management and operations of the Vaccine Research Center (VRC), who recently passed away. Before joining VRC, Dr. Harvey served as a special assistant in Dr. Fauci’s office where she helped coordinate NIAID’s interagency influenza activities. She will be missed.

Dr. Michail Lionakis, chief of the Fungal Pathogenesis Unit, Laboratory of Infectious Diseases, and Dr. Kanta Subbarao, chief of the Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, were recently elected fellows of the Infectious Diseases Society of America.

Rear Admiral Susan Orsega has been appointed chief nurse officer in the U.S. Public Health Service. Susan currently serves as a senior program management officer in the Division of Clinical Research.

NIH’s Ebola Clinical Research Response Team, headed by Dr. Cliff Lane, received the 2015 HHS Secretary’s Award for Distinguished Service. The Team, which included 35 members from NIAID, received the award for rapidly mounting a clinical research response during the 2014-2015 Ebola outbreak.

Meetings and Events

On June 14, the Cuban Minister of Public Health, Dr. Roberto Tomás Morales Ojeda, and his delegation visited NIH. Dr. Fauci presented an overview of NIAID research, including our research response to Zika. Dr. Ojeda and HHS Secretary Burwell signed a Memorandum of Understanding to establish coordination across a broad spectrum of public health issues.

On August 12, Dr. Fauci met with a group of reporters from Haiti who were in Washington on a visit sponsored by Voice of America. He discussed NIAID research with an emphasis on Zika and on TB and HIV research in Haiti.

Dr. Fauci’s November 2015 TEDMED talk “Embracing Flexibility as a Matter of Scientific Principle” is available online at the TEDMED channel on YouTube. He discusses the need for flexibility as well as scientific rigor when designing and implementing clinical trials in response to a public health crisis such as the HIV/AIDS epidemic.

Budget Update

In February, President Obama released his FY 2017 budget request to Congress, which provides NIH with a 2.6 percent or $825 million increase over FY 2016. Dr. Fauci noted that most institutes and centers have a flat budget, and the 2.6 percent increase will go to NCI for the National Cancer Moonshot Initiative and to NIH’s Office of the Director for the Precision Medicine and BRAIN Initiatives.

NIH most likely will start FY 2017 operating under a continuing resolution that usually extends funding at the same level as the previous fiscal year.

NIAID will begin FY 2017 with a conservative funding approach. Our interim R01 payline will be the 10 percentile for non-new investigators and the 14 percentile for new investigators. NIAID does not plan to make programmatic cuts to noncompeting and competing grants. Competing research initiatives will be cut up to 10 percent from their planned budget level. Our estimated success rates for research project grants will be between 20 and 22 percent.

Dr. Fauci gave an update on the budget with respect to Zika virus research. In February, the President requested $1.9 billion in emergency funding for Zika initiatives. Congress has not approved this request. Of the President’s request, NIAID would receive $277 million to support development of medical countermeasures, such as diagnostics, therapeutics, and especially vaccines for Zika and other vector-borne diseases.

In the interim, HHS has realigned funds internally from other research priorities to support the Zika research effort. These funds came to NIAID from three sources: NIAID realigned support from other research priorities, the Secretary repurposed unused Ebola funds, and the Secretary used her one percent transfer authority taking funds from other NIH institutes and agency programs.

Legislative Update

The Zika virus outbreak in the Americas continues to draw intense Congressional attention.

On June 8, Dr. Fauci briefed the Senate Democratic Steering and Outreach Committee on NIAID efforts to address the Zika virus. CDC Director Dr. Tom Frieden, Secretary of Health for the Commonwealth of Puerto Rico Dr. Ana del Carmen Rίus, and representatives of research and advocacy organizations also participated.

On June 22, Dr. Francis Collins and Dr. Fauci participated in a Congressional “Meet and Greet” breakfast organized by Representative Peter Sessions. Dr. Fauci answered questions about the evolving Zika outbreak and provided an update on NIAID’s effort to develop Zika vaccines.

On August 19, Dr. Fauci briefed staff of members of the Congressional Progressive Caucus and updated them on NIAID’s efforts to better understand the Zika virus.

On August 24, Dr. Fauci participated in a telebriefing on Zika for bipartisan members of the House Energy and Commerce Committee.

On September 7, Dr. Fauci briefed the House Democratic Budget Group and provided an overview of the current Zika epidemic.

On September 8, Dr. Fauci joined other HHS representatives in a briefing on Zika for staff of the House Democratic Caucus to highlight HHS’s response to the Zika epidemic. On the same day, he also updated members of the Senate Democratic Caucus on the urgent need for Congress to pass a supplemental appropriation allowing NIAID to move forward with large-scale testing of Zika vaccine candidates that are more promising.

On September 9, Dr. Fauci met with Maryland Senator Ben Cardin during his visit to NIH. They discussed NIAID’s Zika response activities.

Dr. Fauci recognized NIAID staff who have participated in Congressional hearings and briefings on Zika and antimicrobial resistance, including Dr. Cristina Cassetti, Virology Branch, DMID; Dr. Hilary Marsten, global health advisor in Dr. Fauci’s office; Dr. Dennis Dixon, chief of the Bacteriology and Mycology Branch, DMID; and Dr. Michael Kurilla, director of the Office of Biodefense Research Resources and Translational Research, DMID.

A Congressional delegation visited Monrovia, Liberia, and were briefed on the status of Ebola clinical research in the PREVAIL trials.

Other Information Items

Dr. Fauci began with an update on Zika, presenting statistics on reported cases, which include both travel-associated Zika and local transmission, in the U.S. and U.S. territories.

With the blood supply being vulnerable, FDA has recommended testing for the Zika virus in all donated blood and blood components in the U.S. This serves two purposes, keeping the blood supply safe and giving an idea of prevalence of infection in a community.

HHS declared a public health emergency in Puerto Rico in response to the Zika outbreak, with four to five percent of its population getting infected each month.

Dr. Fauci gave an overview of Zika-related activities that have occurred over the last several months, including White House and Congressional briefings and meetings, a media briefing at the Bipartisan Policy Center at the National Press Club, a discussion at the Aspen Ideas Festival, and promising studies and research.

Dr. Fauci continued with an HIV/AIDS update mentioning that this summer was the 35^th anniversary of the recognition of this syndrome. He presented HIV/AIDS global and U.S. statistics, including people living with HIV, people who have died of AIDS, and newly diagnosed HIV infections. Dr. Fauci provided a brief summary of HIV/AIDS meetings and visits that took place in Durban, South Africa, over the summer and results of a few significant studies.

He concluded by giving updates on Ebola, yellow fever, and norovirus.

III. Guest Speaker—Steven Holland, M.D., director, Division of Intramural Research, NIAID

Dr. Holland began by giving some background information on how the Division of Intramural Research (DIR) operates. He then presented DIR’s priorities, which include:

• Transformative medicine and biomedical research
• Bench-to-bedside research using NIH’s Clinical Center and NIAID domestic and international sites
• Responding to public health threats
• Partnering to advance vaccines, therapeutics, and diagnostics for infectious and immunologic diseases

Dr. Holland gave an update on DIR personnel. He mentioned the passing of Dr. William Paul, the upcoming departure of Dr. Kanta Subbarao to become director of the WHO Influenza Center in Melbourne, and Dr. Kathryn Zoon’s retirement.

Dr. Maureen Goodenow is now the NIH associate director for AIDS research and director of the Office of AIDS Research. In October, Dr. Luigi Notarangelo will join the Laboratory of Host Defenses, where he will focus on immunodeficiency research, transplantation, and gene therapy.

Dr. Holland recognized newly tenured scientists, Dr. Stefan Muljo, Dr. Helen Su, and Dr. Karin Peterson. He also acknowledged DIR scientists who received distinguished honor and awards—Dr. Cliff Lane, Dr. Ron Germain, and Dr. Peter Crompton, and three scientists who were recently elected to the American Academy of Microbiology—Dr. Yasmine Belkaid, Dr. Jason Brenchley, and Dr. Kim Hasenkrug.

Dr. Holland highlighted some of DIR’s scientific research in the areas of immunology, virology, bacteriology, and vaccinology. He concluded by summarizing DIR’s future directions.

IV. Report of the Allergy, Immunology, and Transplantation Subcommittee—Daniel Rotrosen, M.D., director, DAIT

Dr. Rotrosen welcomed the subcommittee members to the 184^th meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting:

Dr. Rotrosen presented the following new staff members, scientific and Division activities:

Staff and Organizational Changes

Susan Perry, R.N. Susan Perry joined the Allergy, Asthma, and Airway Biology Branch as a nurse consultant in July 2016. She received her bachelor’s degree in nursing from the University of Oklahoma. Prior to joining DAIT, Ms. Perry was a research nurse specialist at NCI, working with the Thoracic and GI Oncology Branch, responsible for protocol development and implementation.

Scientific Initiatives

Notice to Include Zika Virus Infections in Applications Submitted in Response to RFA-AI-16-001, "Immunity to Neonates and Infants (U01)" (NOT-AI-16-055): The purpose of this notice is to inform potential applicants of a clarification regarding the funding opportunity announcement (FOA) RFA-AI-16-001, "Immunity in Neonates and Infants" (U01). When this FOA was originally released, the effects of Zika virus infection on the developing fetus, or possible effects on neonatal/infant immunity, were not appreciated.

Notice to Extend the Application Due Date and Expiration Date for RFA-AI-16-007, "Nonhuman Primate Transplantation Tolerance Cooperative Study Group (U01)" (NOT-AI-16-068): The purpose of this notice is to extend the application due date and expiration date for RFA-AI-16-007, "Nonhuman Primate Transplantation Tolerance Cooperative Study Group (U01)" by one week.

Notice to Extend the Application Due Date and Expiration Date for RFA-AI-16-008, "Nonhuman Primate Transplantation Tolerance Cooperative Study Group (U19)" (NOT-AI-16-069): The purpose of this notice is to extend the application due date and expiration date for RFA-AI-16-008,"Nonhuman Primate Transplantation Tolerance Cooperative Study Group (U19)" by one week.

Systems Approach to Immunity and Inflammation (U19) (RFA-AI-16-050): The purpose of this FOA is to develop a comprehensive understanding of innate and adaptive immune responses triggered by pathogens, adjuvants, or vaccines using a systems biology approach. The basis of the research program will be to conduct forward genetic screens of mutant or genetically diverse mice, combined with systems level analysis, to identify previously unappreciated key immune regulatory genes, signaling pathways, or mechanisms, and will include validation of these pathways in human cells and tissues.

Emerging Science and Technology in Transplantation (U01) (RFA-AI-16-042): This FOA seeks applications from institutions or organizations to participate in a cooperative research group focused on transplantation immunology research in three priority areas: 1) microbiota, 2) intravital imaging, and 3) targeted therapeutic delivery. And to stimulate and support innovation in transplantation immunology through the application of scientific developments and technologies that have not been widely used in transplant immunology research and the formation of new interdisciplinary collaborations.

Maintenance of NIAID Specific Pathogen-Free Macaque Breeding Colonies (RFP-NIAID-DAIT-NIHAI2016062): This request for proposals details the scope and functions to be performed by the contractor to maintain and provide all aspects of care for Government-owned SPF Indian-origin rhesus macaque (Macaca mulatta) and two country origin cynomolgus macaque (Macaca fascicularis) breeding colonies.

Small Grants on Primary Immunodeficiency Diseases (R03) (PA-16-372): This FOA will support small grants on primary immunodeficiency diseases focusing on ex vivo studies with human specimens and on studies with current or new animal models including novel clinical strategies for detecting, identifying the molecular basis of, or developing innovative therapies for primary immunodeficiency diseases. In addition, this FOA aims to encourage analyses of clinical data and samples maintained in primary immunodeficiency registries, consortium databases, and repositories to address questions relevant to primary immunodeficiency research.

Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21) (PA-16-373): The purpose of this FOA is to support innovative exploratory/developmental investigations on primary immunodeficiency diseases focusing on ex vivo studies with human specimens and on studies with current or new animal models including novel clinical strategies for detecting, identifying the molecular basis of, or developing innovative therapies for primary immunodeficiency diseases.

Division Activities

Allergy, Asthma, and Airway Biology Branch

Insights to Asthma Severity from the Inner-City Asthma Consortium. On May 15, 2016, NIAID organized a session on asthma severity as part of the annual meeting of the American Thoracic Society (ATS), in San Francisco, California. Inner City Asthma Consortium (ICAC) researchers presented how host and environmental factors work in concert to determine asthma severity, how IgE levels influence viral infection and illness in asthmatics, and the role of dendritic cells in antiviral immunity.

State-of-the-Art Investigations into Chronic Rhinosinusitis and Nasal Polyposis. On June 13, 2016, NIAID organized a session on chronic rhinosinusitis and nasal polyposis as part of the annual meeting of the European Academy of Allergy and Clinical Immunology (EAACI) in Vienna, Austria. The session featured NIAID researchers who presented on the role of ILC2 cells in nasal polyposis and allergic rhinitis, the role of PGD-2 and other arachidonic acid metabolites in nasal polyps, on aspirin exacerbated respiratory disease, and on the mechanisms of inflammation and remodeling in nasal polyposis.

Basic Immunology Branch

Human Immunology Project Consortium (HIPC) II Assay and Bioinformatics & Biostatistics Subcommittee Meeting. On June 7, 2016, NIAID held a subcommittee meeting in Rockville, Maryland. The main HIPC program focused on developing molecular profiles of the varied human immune responses to pathogenic infection or vaccination. The functions of the HIPC II Assay and Bioinformatics/Biostatistics Subcommittees are to promote the development of cross-center collaborative projects, bioinformatics tools and related resources to advance human immunology research.

DAIT Immune Epitope Programs Annual Progress Meeting. On July 13 and 14, 2016, the annual meeting of the B Cell and T Cell Epitope Discovery Programs and the Immune Epitope Database and Analysis Resource was held in Rockville, Maryland. Investigators provided updates from the B Cell Epitope Discovery and T Cell Epitope Discovery contracts. At the end of the second day a working group meeting was held with NIAID staff and external working group members to provide feedback to NIAID on the progress and success of the program overall.

Adaptive Immune-Receptor Repertoire (AIRR) Community Meeting: Progress in Standards, Tools, and a Common Repository for AIRR Data. On June 27 to 30, 2016, the AIRR Community meeting was held in Rockville, Maryland. One goal of the meeting was outreach and inclusiveness to maximize input into this developing community and field. A second goal was to educate attendees (approximately 120) about AIRR data acquisition, analysis, and use. The third and primary goal of the meeting was to finalize the recommendations of working groups that emerged from the 2015 AIRR meeting. Working groups reporting at the meeting included a Common Repository Working Group, a Minimal Standards Working group, and an AIRR Resources and Tools Working Group. Attendees at the meeting reviewed an outline for an AIRR Community White Paper providing guidelines and standards for deposition of AIRR data in public databases for use by the broader research community. DAIT and DAIDS supported this meeting, as this field is relevant to both missions and a growing scientific field and opportunity.

Autoimmunity and Mucosal Immunology Branch

Mechanisms that Drive Human Autoimmune Disease and Implications for Prevention. On June 22, 2016, NIAID sponsored a symposium in Boston, Massachusetts. The session highlighted cutting-edge research results from the Cooperative Study Group for Autoimmune Disease Prevention. Investigators presented data and progress on the evolution of autoimmune responses in rheumatoid arthritis and systemic lupus erythematosus, immunologic processes that drive the pathogenesis of type 1 diabetes, and genetic and epigenetic factors that drive autoimmunity.

Preparation and Review of Your NIH Grant Application. On June 24, 2016, NIAID held a workshop in Boston, Massachusetts. The workshop provided participants with an overview of the preparation and review of NIH grant applications, featuring a mock study section staffed by FOCIS investigators to illustrate critical points evaluated by peer reviewers.

Radiation and Nuclear Countermeasures Program (RNCP)

Dosimetry Harmonization Workshop. On August 29 and 30, 2016, the RNCP organized a meeting in Rockville, Maryland. The purpose was to provide a forum for researchers to share their current methodologies on dosimetry and to determine how dosimetry consistency can be implemented across the program. This workshop was held in an interactive format that allowed for open discussion and brainstorming to explore problems faced in this area of research. Publication of a meeting report is planned to share concrete tools and information with a wider audience.

Medical Management of Radiation Casualties Workshop: Where Research and Usage Meet. On July 18 and 19, 2016, the RNCP and Radiation Injury Treatment network sponsored a workshop in Rockville, Maryland. Participants discussed existing gaps between operational needs and medical countermeasure development, including preclinical models, and examined specific areas for further research and development based on expected needs within the first few days following a nuclear detonation, versus expected needs a few weeks post-incident. The ultimate goal was to refine the application of animal models to match operational needs for medical management.

Concepts Presented for Clearance

FY 2018 Research Concept Clearances

Development of Cellular Therapies for Treatment/Mitigation of Radiation Induced Injuries: This initiative will support the research and development of cellular therapy countermeasures against radiation injury.

The subcommittee endorsed and unanimously approved this initiative.

V. Report of the Microbiology and Infectious Diseases Subcommittee–Irene Glowinski, Ph.D., acting director, DMID

Director’s Report

Dr. Irene Glowinski, acting director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on September 12, 2016. Dr. Glowinski acknowledged the three Subcommittee members who were retiring after today’s meeting, Drs. Robert Belshe, Diane Griffin, and Norm Baylor, and thanked them for their service. She also introduced Dr. Joe Larsen, who was representing the Biomedical Advanced Research and Development Authority (BARDA). She then referred to the branch chiefs and office directors to introduce new staff in their respective programs.

Program, Scientific, and Budget Updates

Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X): BARDA/NIAID Collaboration – Dr. Dennis M. Dixon

Dr. Dixon described the recently launched Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), a noted priority in the 2015 US National Action Plan on Combating Antibiotic-Resistant Bacteria (CARB), that calls for the development of a biopharmaceutical accelerator to stimulate preclinical product development and advance high-quality antibacterial products towards entry into human testing. BARDA is providing funding support for this unique public-private partnership, which aims to spur innovative and promising solutions to antibiotic resistance. NIAID will provide in-kind research support through access to DMID’s comprehensive suite of preclinical services, which includes technical expertise, to select projects supported by CARB-X for early-stage antibiotic drug discovery and product development activities. BARDA made the award to Boston University, and several DMID staff members, including Drs. Dixon, Mike Kurilla, Rose Aurigemma, and François Franceschi, are actively involved in the effort.

Concepts Presented for Clearance

The following fiscal year 2018 concepts were presented to the Subcommittee:

Development of Medical Countermeasures for Biothreat Agents, Antimicrobial-Resistant Infections, and Emerging Infectious Diseases – the objective of this concept is to advance the translation of promising therapeutic, prophylactic, and diagnostic products against biothreat pathogens, antimicrobial resistant bacteria, and emerging infectious diseases, from lead candidate to first-in-human clinical trials. The concept was enthusiastically received by the DMID Subcommittee, who recognized the past successes of the program and acknowledged the important gap the concept fills in the infectious diseases, advanced product development arena. A question was asked regarding the priorities and criteria considered by NIAID staff when developing solicitations and making awards. Program staff explained that, having learned from the Ebola and Zika virus outbreaks, the Division would focus on high-priority products that would address the current public health demands at the time of solicitation and award. The mechanism used to solicit proposals would be tailored to prioritize the pathogens that are most in need of medical countermeasures. The Subcommittee also asked about coordination with other agencies to reduce overlap. Program staff described the frequent interactions and portfolio reviews that take place between NIAID, BARDA, the Department of Defense, and the Defense Threat Reduction Agency (DTRA), and noted that all of these organizations strive to synergize support for promising countermeasure concepts to ensure that no funding overlap exists. The concept was unanimously approved by the Subcommittee.

Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antimicrobial-Resistant Gram-Negative Bacteria – the objective of this concept is to support milestone-driven projects focused on developing and utilizing novel predictive models, research tools, assays or platforms aimed at better understanding the rules and compound properties governing the penetration and efflux of drug-like small molecules in Gram-negative bacteria. The proposed initiative is targeted to a selection of pathogens that pose a significant public health threat because of documented resistance to available antibiotics (carbapenem-resistant Enterobacteriaceae (CREs), multidrug resistant (MDR) Acinetobacter and MDR Pseudomonas aeruginosa), and would support the early preclinical development of Gram-negative antibacterials based on the tools and/or models developed. The Subcommittee wholeheartedly supported the concept. One Subcommittee member requested clarification about whether responsive applications would need to address all (and only) the pathogens mentioned. Program staff clarified that responsive applications would need to address at least one of the listed pathogens. Another Subcommittee member commended the existence of an initiative that while tackling a basic science question could also inform the development of new classes of antibacterials. The Subcommittee unanimously approved the concept.

Partnerships for Development of Vaccines to Prevent Mycobacterium tuberculosis Infection and/or Tuberculosis Disease – the objective of this concept is to support milestone-driven research projects focused on establishing proof-of-concept for and/or preclinical development of promising candidate vaccines against Mycobacterium tuberculosis (Mtb) infection and/or TB. Applicants would be required to document availability of one or more favorable candidate(s) with demonstrated capacity to elicit an immune response in a relevant animal model for Mtb infection and/or TB disease. The concept was received with enthusiasm by the Subcommittee. Subcommittee members commented that the proposed initiative is important and timely, would advance development of preclinical TB vaccine candidates towards licensure, and increase the pipeline of clinical candidates. A suggestion was made to encourage the use of more predictive animal models when testing new TB vaccine candidates for vaccine efficacy. Another Subcommittee member suggested that Program staff ensure that this effort is complementary to and not duplicative of vaccine research and development activities supported by other funders, such as the Bill and Melinda Gates Foundation. The concept was unanimously approved by the Subcommittee.

Development of Multipurpose Prevention Technologies: A Strategy for the Prevention of STIs – the objective of this concept is to advance the development of Multipurpose Prevention Technologies (MPTs), products that women can use to prevent STIs, HIV, and unintended pregnancies. The goal is to stimulate mid-stage translational, milestone-driven research that will further the preclinical development of these products. The Subcommittee asked for more details on previous microbicide-type products supported by DMID and the intended duration of protection of these new MPTs. Staff clarified that the duration of protection would be dependent on the product and intended use; duration could range from short-term, single-use protection to long-lasting, multiple-month protection. One Subcommittee member voiced support for the concept and asked how related efforts were coordinated across the NIH and other agencies since this product class has multiple indications. Staff reported that relevant NIH and agency working groups meet on a regular basis to discuss and coordinate efforts. Overall, the concept was well received by the Subcommittee, and was unanimously approved.

VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., director, DAIDS

Director’s Report

Dr. Dieffenbach paid tribute to Elizabeth Hope Flanagan, a program officer in the Prevention Sciences Program, who lost her battle with colon cancer on July 11, 2016. He recalled that Elizabeth joined the Division in May 2012 and made a significant impact. He described her as a person who was always in a hurry to get work done, as though she had a premonition of what would befall her. He said that she will be greatly missed and encouraged staff to adopt a philosophy of being more like Liz. Keep the momentum going to the extent you can. That is the way she lived her life, and that is the way colleagues are seeking to remember her.

Dr. Dieffenbach presented certificates of appreciation to people rotating off ARAC: Stephen Mason, Deborah Persaud, and David O’Connor. He introduced Ruth Ebiasah, the new chief for the Office of Clinical Site Oversight’s Pharmaceutical Affairs Branch. She is returning to DAIDS after three years as the DMID pharmacist. Ruth’s doctorate of pharmacy is from Howard University and her master’s in the science of health systems pharmacy administration is from University of Ohio. Additionally, she completed a two-year specialty pharmacy residency at Riverside Methodist Hospital in Columbus, Ohio.

Budget Update

In February, the President announced his FY 2017 budget with a proposed overall 2.6 percent NIH increase, but most money was put into the Office of the Director for Precision Medicine for the Brain Initiative, and the rest went to the Cancer Moonshot for NCI. So far, no appropriations bill has been enacted for the coming fiscal year. The assumption is that NIH will be under a continuing resolution (CR) for three or six months, depending on what gets passed at the end of September. What this means for the grants management component is that NIAID has an FY 2017 interim financial management plan consisting of:

• R01 Payline
• Established PI: 10 percentile
• New PI: 14 percentile
• Noncompeting and competing grants: No adjustments
• Competing research initiatives: Cut up to 10 percent
• Estimated success rates: 20 to 22 percent

In late winter, the President asked Congress to enact an almost $1.9 billion emergency request to help fund activities for the Zika crisis. What was proposed for NIAID was a $277 million request to help advance the vaccine clinical trials that are needed to help combat the crisis. Also, CDC and other parts of the federal government were to receive money to combat the crisis. In the absence of funding coming from Congress, NIAID, working within HHS and the Secretary’s office, moved money around in three ways ‒ NIAID appropriations, leftover Ebola money, and HHS Secretary’s transfer authority ‒ to move funds totaling $92 million to tackle Zika. The vast majority of the money went into the vaccine pool, but also $11 million into diagnostics and therapeutics, and other money into epidemiological studies. Much of the money in the HHS Secretary’s transfer authority came from NIH ICs, such as NCI, NHLBI, and others. Progress has been made. VRC’s DNA vaccine has gone into Phase 1 testing, NIAID is recruiting 80 volunteers, and initial results are expected by the end of calendar year 2016. He discussed the Zika vaccine development timeline and Dr. O’Connor’s preclinical study that applies the preclinical AIDS research approach to maximize macaque model utility in Zika studies.

Scientific and Programmatic Updates

NIH is launching large clinical trials in the form of two trials of antibody-mediated prevention (AMP) testing IV infusions of VRC01, an HIV neutralizing antibody (NAb). In addition, a large-scale HIV vaccine trial, HVTN 702 ‒ a modified RV144 prime-boost regimen ‒ will launch in November in South Africa and will enroll 5,400 men and women between the ages of 18 and 35 years, at risk of acquiring HIV. Two Cabotegravir studies are forthcoming: HPTN 083, a Phase 2b/3 double-blind safety and efficacy study of injectable Cabotegravir compared to daily oral Tenofovir, Disoproxil, and Fumarate/Emtricitabine (TDF/FTC), for PrEP in HIV-uninfected men and transgender women who have sex with men; HPTN 084, a Phase 3 study, currently designed as an open-label safety and efficacy study of long-acting injectable Cabotegravir compared to daily oral TDF/FTC for PrEP in HIV-uninfected women. Another trial is the HIV Open-Label Prevention Extension (HOPE) Phase 3b trial, MTN-025, to assess the continued safety of and adherence to a vaginal ring containing Dapivirine in women. Enrollment began July 2016, with a 2,500 target accrual.

Strategies for a Cure Meeting will be held November 14 to 16, 2016. It will convene members from new Martin Delaney Collaboratories and other grantees to discuss recent progress, priorities for the future, and help facilitate collaborations. He also provided IAS updates on:

• PROMISE ‒ HIV Therapy for Breastfeeding Mothers Can Virtually Eliminate Transmission to Babies
• ASPIRE ‒ Vaginal Ring May Cut HIV Infection Risk if Used Consistently

His report ended with a Facebook image he participated in for LIVE AIDS 2016 at the July Durban, South Africa IAS conference.

DAR/DAIDS Functional Integration: The Scientific Agenda from Discovery to Implementation

Dr. Dianne Rausch, director, Division of AIDS Research (DAR), National Institute of Mental Health (NIMH), provided an overview of the DAR mission, a model for an integrated agenda, highlights of DAR research, and suggestions for moving forward. The DAR mission is to reduce the global incidence of HIV/AIDS, decrease HIV/AIDS related morbidity and mortality, and advance HIV/AIDS cure research. The DAR priority areas are basic and applied behavioral and social science, basic and clinical neuroscience of HIV infection to understand and alleviate the consequences of HIV infection of the CNS, and mental health research to improve HIV treatment and prevention. The DAR/DAIDS scientific agenda from discovery to implementation consists of:

• Discovery science: ARV treatment, vaccines, biomedical prevention, basic behavioral and social science research (BSSR)
• Translational science: clinical trials and applied BSSR
• Implementation science: integrated behavioral, biomedical, and structural approaches

An example of BSSR in the discovery phase of research is an approach to understand and addresses stigma and discrimination. There are multiple dimensions of HIV-related stigma, which must be understood in order to develop impactful interventions. Dr. Rausch cited a recent study on the negative effects of internalized HIV-related stigma on ART adherence in women, and discussed how such internalized stigma affects and is affected by social support, depressive symptoms, and adherence. An example of the translation phase of BSSR targeting adherence would include an interconnected sequence of adherence psychometrics, adherence support process, support fidelity, biometrics, and analytics, exemplified by an integrated framework for adherence support and measurement identified in clinical trials of ARV-based vaginal rings.

In making the case for implementation science research in HIV/AIDS, Dr. Rausch described the dual pathway to controlling and ultimately ending the AIDS pandemic: improving implementation of current interventions, discovery of new interventions, and the combination of these into the synthesis of treatment and prevention. She discussed the implementation of the Treat All policy among adults and adolescents living with HIV in low-income, middle-income, and Fast-Track countries as of July 2016. The use of implementation science is utilized to test models for care and task-shifting. As an example of biobehavioral implementation research, she cited a prospective implementation study on the integrated delivery of ART and PrEP to HIV-1 serodiscordant couples in Kenya and Uganda. Another example is PrEP: the gap from evidence to practice, and pointed out that PrEP is highly efficacious but underused.

Dr. Rausch discussed DAR NeuroAIDS highlights and research on the neurological complications of HIV infection:

• Mechanisms of neuropathogenesis
• Therapeutic strategies to prevent or reverse CNS dysfunction
• HIV cure research including eradication of HIV from the CNS
• Neurotoxicity of ART regimens

As an example of NeuroAIDS discovery to translation, she cited the development of cambinol, which shows neuroprotective properties and improves cognitive function, and the finding that macrophages sustain HIV replication in vivo independently of T cells. She discussed new frontiers in neuroscience with a multi-modal imaging setup and fiber-optic-based microscope design, and the use of neuroimaging in diagnosis of mental illness.

Concluding, Dr. Rausch offered strategies and science for moving forward:

• Strategies:
• Enhanced coordination for integrative science with DAIDS and partner ICs
• Expand successful global trans-agency partnerships with PEPFAR, CDC, HRSA, WHO, USAID, UNAIDS, BMGF, AVAC, IPM, MSF and AAVP.
• Integrated science: To achieve the NHAS and WHO goals:
• Biobehavioral execution of prevention/treatment trials from Phases 1 to 4
• Cure agenda team science, which combines discoveries from biomedical, behavioral, Neuro AIDS, and participatory research to advance eradication
• Targeted implementation research on HIV Care Continuum and PrEP to optimize public health impact

Questions and Answers:

Q: PrEP exemplifies the gap between clinical science and implementation. At IAS, statistics show nearly 80,000 have accessed PrEP. This is more than the 25,000 estimate you mentioned. Much of this is related to local efforts to decrease the gap.
A: Yes.

Q: What testing was used with the sex workers? And how was it implemented?
A: It was a simple self-test, very easy to use, and a lot of safety measures were in place. They had a hotline for potential negative impacts. Counselors tracked people to ensure they followed treatment. It was a pilot. They tried to educate the women on how to do this. It was encouraging that those women actively took up the test and distributed them.

Q: 1) What is the neurological research at the basic level? 2) At the applied science level. Is it oriented towards access to clinical and biomedical interventions? 3) Is implementation research mostly focused on sexual risk/HIV risk behavior change? What is your group’s resource allocation across those categories and other research areas?
A: In the early NIMH days, research was essentially allocated 60 percent to behavioral science and 40 percent to neuroscience. As we moved forward, we identified new priorities. As our priorities have evolved to include a broader breadth, we still try to keep that two-thirds/one-third ratio, but it is difficult because mental health work sometimes fits into basic and sometimes into behavior. Now, we try to manage it by looking at the OAR strategic priorities; be aware if those buckets change, determine what drives it and feed that back. One year we may fund more basic neuro because of opportunities, and the next year expand more into behavioral. But what do we consider implementation science? Is it basic or behavioral? Most of it is behavioral, but there are some basic science opportunities. The military work is really translational in implementation because they are treating acute infections. So, how does that fit in? It is an evolving process.

Because budget has been flat lined, we continuously do program analysis to redirect funds to new priorities, which by necessity implies needing to decrease funding in areas where we feel there is less critical need. It is not a simple process. It occupies a great deal of time.

Q: Marketing of sexual microbicide products was viewed as an adherence barrier. Products were not sexy looking. To what extent is marketing and branding considered part of implementation revision? Is that in your portfolio’s scope, or does that fall somewhere else?
A: Marketing is critical. Part of it falls into our work, trying to figure out if people will use a product. People sometimes say yes, but don’t use it. Finding out why is a basic behavioral and social science question. We consult with marketing people. We use behavioral economics investigations to try to understand what drives decision making. The behavioral and social science agenda is evolving to accommodate such complicated matters. You might have the best product in the world, and it might be 100 percent effective, but if they do not like the way the ring feels, they will not use it. That is a big part of what we do, but it is complicated. It has to be done in a bigger context than just our little group.

Comment: Many of us in the field are concerned about the way new products look. USAID is funding consumer-oriented work with prevention products, tablets, and microbicides to get end-user input into the way packaging would work or how it would be rolled out. The Office of AIDS Research, through a supplement from NICHD, provided funds to get on-the-ground input from the youngest members about challenges they have had with oral PrEP or vaginal rings. What is a value proposition for them? How do they see the product? I think their input is critical to how products are presented to young women. It is an important and interesting question.

AIDS Vaccine Research Subcommittee (AVRS) Update

Dr. Jim Bradac, executive secretary to AVRS, which is an ARAC subcommittee. AVRS changes: Georgia Tomaras became chair. George Lewis and Leo Stamatatos are new members, and Aftab Ansari will serve another three years, is now on ARAC, and will be AVRS liaison to ARAC. Dr. Bradac pointed out the ex-officio members that are PIs on five of AVRS’s largest grants. Those grants are: the Nonhuman Primate Consortia − Rama Amara and Eric Hunter are PIs on the Emory Consortia, Jeff Lifson is a member of the Harvard Consortia, Dan Barouch represents the Scripps CHAVI-ID, Barton Haynes represents the Duke CHAVI-ID, and Larry Corey represents HVTN. Much of what AVRS talks about is the research carried out by these groups. It is hoped that this facilitates collaborations between the grantees.

The AVRS meeting on June 7 and 8, 2016 covered:

• Innovation for HIV Vaccine Discovery Program (IHVD)
• Grantee presentations
• Preclinical Research Update
• Consortia for Innovative AIDS Research in Nonhuman Primates
• Clinical Analysis of Germline-Targeted Immunogens
• HVTN 100 Update
• OAR Advisory Committee Meeting Summary
• DAIDS Vaccine Translational Research Update
• Duke Human Vaccine Institute Manufacture Facility Update

Dr. Bradac focused on the IHVD Program, the Preclinical Research Update, and the HVTN 100 Update. He listed the IHVD grantee presenters and the topics they discussed, and pointed out that AVRS members were complimentary of the quality of the science performed under the IHVD program and recommended that the program be continued and given a high priority in the IC’s future FY discussions.

Dr. Bradac described the Consortia for Innovative AIDS Research in Nonhuman Primates (CIAR), reporting two awards were made in April/May 2016:

• Dan Barouch (Beth Deaconess Medical Center)/Louis Picker
• Eric Hunter/Rama Amara (Emory University)

He summarized Dr. Lifson’s presentation on CIAR as having two foci. Focus 1: “PREVENTION”: Prophylactic Vaccination: block initial infection or prevent establishment of persistent systemic infection. Focus 2: “THERAPY/CURE:” Therapeutic vaccines and engineered T cells, together with sanctuary disruption and potentially, latency reversal, can contribute to virus eradication/control strategies.

He also summarized Dr. Hunter and Dr. Amara’s presentation on the Emory Consortium for Innovative AIDS Research in Nonhuman Primates. Focus 1: Mechanisms of Enhanced Vaccine Protection. A balanced anti-HIV response is critical, involving durable humoral immunity, tissue resident memory CD8 T cells, and balanced humoral and cellular immunity. Focus 2: Mechanisms of Reservoir Eradication. A combination of immunotherapeutics is required.

Overall, AVRS members were impressed with work carried out through the first iteration of these consortia, and equally impressed with the plan outlined by the two CIARs. Particularly gratifying is how the CIAR investigators have linked into the CHAVI-ID programs as primary collaborators and as core members of their development teams.

He summarized Dr. Mary Marovich’s HVTN 100 Update and Next Steps. The strategy for the Phase 3 program has been the sequence of:

• HVTN 097: a Phase 1 study to evaluate the immunogenicity of the RV144 vaccine regimen in South Africa
• HVTN 100: a Phase 1 study to evaluate the safety and immunogenicity of clade C products and to decide whether to proceed to Phase 2b/3 based on predetermined go/no-go criteria
• A Phase 2b/3 randomized controlled study assessing efficacy and safety with the goal of supporting licensure.

This sequence was underpinned by community, regulatory, and government stakeholder engagement.

The HVTN 100 results:

• HVTN 100 passed all four predefined criteria established for moving the regimen into an efficacy trial called HVTN 702.
• The four criteria were based upon immune responses associated with Correlates of Protection in RV144.

Dr. Bradac reiterated the criteria required to move into efficacy testing and showed that HVTN 100 exceeded RV144 in each criterion. The HVTN 100 conclusions were:

• The level of immune responses to these key immunogenicity markers allows assessment of Correlates of Protection in the HVTN 702 design.
• Funders/Partners agree to proceed with HVTN 702; anticipate opening in October/November 2016.

HVTN 702 is not an attempt to reproduce RV144:

• Vaccine inserts are different (clade C-based vs. clade E)
• Adjuvant is different (MF-59 vs. alum)
• HLA differences in Africa vs. Thailand
• Routes of transmission may be different in the two populations

Future AVRS meeting dates:

• September 2016 - No meeting planned
• January 31 and February 1, 2017
• June 2017 - No meeting planned
• September 12 and 13, 2017

Concepts Presented for Clearance

Basic Sciences Program (BSP)

Detection of HIV for Self-Testing ‒ presented by Dr. Diane Lawrence for FY 2018
Dr. Lawrence explained that the purpose of this concept is to develop innovative diagnostic technologies to allow individuals to self-test during the early stage of HIV infection, or monitor for viral rebound after stopping therapy or developing resistance. This is proposed as a PAR, using an R61/R33 innovation grant mechanism. This would allow an initial two to three years of funding (R61), followed by a second phase (R33), contingent upon meeting predetermined milestones. The R61 phase provides milestone-driven early-stage technology and assay development. The R33 phase provides continued optimization of assay approach and validation studies with diverse clinical samples. This is a new initiative, with a maximum award of five years, combined for both phases, and the total funding available for the first year is $2.64 million. The program expects to fund between three and five awards.

The WHO definition of self-testing ‒ “a process in which an individual who wants to know his or her HIV status collects a specimen, performs a test, and interprets the result by him or herself, often in private.” She pointed out that current HIV self-tests detect antibody responses and are limited by an inability to detect either initial peak viremia or viral rebound due to drug resistance, poor treatment adherence, or reactivation of the latent reservoir and loss of viral control following treatment interruption. Sensitive and accurate tests for direct HIV detection require access to either expensive equipment in a laboratory or hospital, or a point-of-care assay that requires a trained individual to administer the test and read results.

One major goal of this initiative is to develop technologies that could lead to a self-testing platform for direct detection of acute early-stage HIV infection. A second major goal is to develop assays that could be used repeatedly over long periods of time to monitor HIV rebound, whether due to treatment interruption, such as in a clinical trial for a curative strategy; poor adherence; or emergence of drug resistance. The timing of HIV rebound is unpredictable and viral load increases quickly, so regular testing is necessary to monitor rebound. In 2014, UNAIDS announced goals for global increases in HIV testing, treatment, and suppression. Self-testing could increase the number of people who are aware of their HIV status. This could encourage earlier treatment, resulting in reduced transmission, a smaller reservoir, and improved clinical outcomes. Once treatment is initiated, better viral load monitoring would be expected to improve viral suppression.

Dr. Lawrence said there are three major reasons that now is the right time for this initiative: 1) Reports suggest increased acceptance of HIV self-testing worldwide; 2) Growing interest in personal health monitoring; 3) Recent developments in molecular detection technologies, such as microfluidics, which can manipulate small volumes of fluids and amplify RNA without electricity, synthetic biology approaches that create molecular circuits to detect a specific pathogen, and advances in paper-based analytic materials that go beyond lab-on-a-chip and allow readout without a need for special equipment. Dr. Lawrence emphasized that they want to: 1) stimulate basic research partnerships to develop early-stage platforms for simple, sensitive HIV detection and 2) encourage cross-disciplinary collaborations among virology, microfluidics, nanotechnology, bioengineering, synthetic biology, and manufacturing technology. She emphasized a focus on research innovation, not product development. Research could explore potential biomarkers for HIV and compare results with different biofluids. The ultimate goals for a self-test are:

• Sensitive detection of HIV at earliest possible time post-infection or upon rebound
• Simple to use
• Convenient sampling
• Easy to repeat
• Relatively inexpensive

They envision successful research leading to the later development of a compact self-testing device similar to a glucose monitor or a simple disposable device similar to a pregnancy test.

Pre-ARAC Reviewers, Dr. Amanda Castel and Dr. Sally Hodder, recommended approval and their comments were reviewed in the slide presentation. Further questions and answers included the following:

Q: The division of the timing of the R61/R33, does it have a fixed time and fixed criteria for moving forward into the second phase?
A: No final decision yet. One option is to have the R61 up to three years. It could be less time. Criteria would need to be defined in the application. We do not want to be overly prescriptive as to what those would be.

Q: Do you anticipate that some would fall out if you were to award five for the first R61?
A: Yes, that would be likely. It would be on a case-by-case basis.

Q: The currently FDA-approved self-testing kit has not sold as well as anticipated. Figuring out the obstacles there might help basic science design. The CDC completed a fairly large study in which gay and bisexual men were sent testing kits over the internet and then evaluating the quality of assurance on that oral and finger stick test. Users were sharing them with friends. They assessed changes in sexual behavior, serosorting, and whether their friends were using the test. This a great question: How do we essentially have accurate self-testing as close as possible when the time of viremia occurs? But also, what are the test characteristics that would have people use it?
A: Exactly.

Ballot Voting Outcome:
12 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Therapeutic Research Program (TRP)

Dysregulation of Immune Cell Regulatory Pathways by Mtb in the Context of HIV Infection – presented by Dr. Daniel Frank
The purpose of this initiative is to identify targets and potentially to favorably modify pathogen-induced immune cell dysregulation in order to accelerate development of innovative host-directed therapy (HDT) agents and vaccine strategies. They will look at core cells’ regulatory pathways that TB disrupts to create an environment amenable to host colonization and infection. They have chosen the RFA mechanism, an R61/R33, two phases. It is a new initiative. The first year total cost is $2.7 million, with an additional $0.5 million from DMID. There will be a total of four awards: four for the R61, with half expected to move on to the R33 phase. The duration is two to five years, with a two-year R61 phase, followed by a three-year R33 phase.

Improving TB treatment is critical to addressing the ongoing pandemic due to long and poorly tolerated regimens exacerbated by HIV co-infection and the emergence of drug resistance. TB drug and vaccine development are inadequate due to the failure of traditional approaches, as well as a lack of incentives for pharmaceutical companies to develop new antimicrobials. The rationale for this initiative is that targeted therapies have revolutionized treatment of many diseases by modulating effects of molecular drivers subverting cell regulatory pathways.

The exploratory phase 1 (R61, 2 years), grantees will:

• Identify changes in regulatory mechanisms in infected immune cells and the subsequent responses of uninfected immune cells
• Determine effects of the identified regulatory change on the capacity of pathogen control/killing and inflammatory response
• Characterize target molecules in these regulatory pathways as potential points of therapeutic intervention

In the evaluatory phase 2 (R33, 3 years), grantees will:

• Develop a strategy for therapeutic intervention of phase 1 identified targets in an appropriate model system
• Evaluate intervention agents targeted to modify pathways for improved host defense and/or control of inflammation

We are looking for specific immune-cell regulatory signaling pathways and molecules altered in expression, function, and/or activity by Mtb infection.

• Epigenetic and other gene expression changes, post-translational modifications, and changes in protein localization and half-life.
• Alterations in molecular regulatory control of immunometabolic checkpoints determining immune cell differentiation and function, antibody-mediated modulation of innate cell immune signaling and function, immune cell co-receptor/ligand checkpoints, and suppressor-cell population induction and activity.

Program is looking for hypothesis-driven research, not large screening endeavors. R33 awards depend on a second phase of funding, completion of phase 1 milestones, program priority, and funding availability.

Dr. Frank described current HDT efforts, including first-generation candidates chosen as anti-inflammatory agents or empirically without a clear mechanism of action. There are four DAIDS and one DMID awards to investigate first generation. DAIDS and the Bill and Melinda Gates Foundation (BMGF) are actively coordinating these efforts, with DAIDS supporting discovery and development, and BMGF partnering primarily for development. No other source currently specifically supports similar approaches.

Pre-ARAC reviewers, Dr. Powderly and Dr. Cara Wilson, recommended approval, and their comments were reviewed in the slide presentation:

Further questions and answers included the following:

Q: Are small animal models acceptable in phase 2?
A: Yes. We leave the door open to different ideas for phase 2. We focus phase 1 on finding core, regulatory pathways and leave the options open for how the investigators approach the interventions to whatever pathway they find.

Q: Would the models be HIV and TB models, or some of them TB models?
A: We could accept a TB-only application to be funded by DMID. DAIDS is primarily interested in HIV/TB.

Q: You say screening is out of scope for phase 2, but wouldn’t that be particularly relevant?
A: Screening is not best done by academics; it is more of a pharmaceutical thing. We are looking for hypotheses-driven research, e.g., further investigation into dysregulated core cell regulatory pathways, as opposed to blind screen looking for random targets. Especially in the TB field, there are not that many good in vitro models. Screening efforts have not been very productive.

Q: I was not thinking of blind screening effort. I was thinking that once you have found a target in phase 1, that you could exploit that target in a directed screen.
A: There are ongoing discussions on future targeted screening. We acknowledge a need for that kind of strategy, but we do not think it fits here.

Ballot Voting Outcome:
12 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Future Meetings:
January 30, 2017 (ARAC)
January 31 and February 1, 2017 (AVRS)
June 5, 2017 (ARAC)
September 11, 2017 (ARAC)

Public Comment
None.

VII. Adjournment

The meeting of the Council adjourned at 3:05 p.m., on Monday, September 12, 2016.

We do hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.

Council will formally consider these minutes at its next meeting; any corrections or notations will be incorporated in the minutes of that meeting.