NIAID Council Minutes: September 17, 2018

The 190th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:30 a.m. on Monday, September 17, 2018, 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 3:15 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.

Meeting Attendees

Council Members Present:

Dr. Raul Andino
Dr. Aftab Ansari
Dr. Michael Brenner
Dr. Amanda Castel
Dr. Mark Feinberg
Dr. Ana Fernandez-Sesma
Dr. Stephen Galli
Dr. John Guatelli
Dr. Sally Hodder
Dr. Marc Jenkins
Dr. Gurjit Khurana Hershey
Dr. Stanley Lemon
Dr. Robin Patel
Ms. Kay Whalen
Dr. Cara Wilson

Ex Officio Members Present:

Dr. Victoria Davey
Dr. Anthony Fauci
Dr. Rima Khabbaz
Lt. Col. Wendy Sammons-Jackson

Ad Hoc Members Present:

Dr. Bernhard Hering
Dr. Bruce Schneider

Council Members Absent:

Dr. Wendy Book
Dr. Karen Nelson

NIAID Senior Staff Present:

Dr. Hugh Auchincloss
Dr. Carl Dieffenbach
Dr. Emily Erbelding
Dr. Matthew Fenton
Dr. John McGowan
Dr. Daniel Rotrosen

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–Emily Erbelding, M.D., M.P.H., 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 4,650 research and training applications with primary assignment to NIAID for a requested amount of $1,700,406,166 in first-year direct costs and recommended approval of 2,002 applications with $615,806,201 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 four new Council members: Dr. Michael Brenner, Harvard Medical School; Dr. Ana Fernandez-Sesma, Icahn School of Medicine at Mount Sinai; Dr. Marc Jenkins, University of Minnesota; and Ms. Kay Whalen, Executive Director, Inc.

He also welcomed two ad hoc Council members, Dr. Bernhard Hering, scientific director of the Schulze Diabetes Institute and professor in the Department of Surgery at the University of Minnesota, and Dr. Bruce Schneider, medical officer and clinical team leader at FDA.

Council members Dr. Karen Nelson and Dr. Wendy Book were unable to attend the meeting.

Dr. Fauci acknowledged the contributions of five retiring Council members—Drs. Wendy Book, Amanda Castel, Stephen Galli, John Guatelli, and Gurjit Khurana Hershey—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 4, 2018 meeting and approved them as written.

Appointments and Transitions

President Trump has nominated Dr. Kelvin Droegemeier to lead the White House Office of Science and Technology Policy.

Dr. Helene Langevin has been selected as the new director of the National Center for Complementary and Alternative Medicine.

Staff and Organizational Changes

In the Division of AIDS, Dr. Adriana Andrade has been named the new chief of the HIV Research Branch in the Therapeutics Research Program.

Dr. Marshall Plaut, an internationally recognized expert on allergic diseases, recently retired from the Division of Allergy, Immunology, and Transplantation (DAIT), after 27 years as chief of the Food Allergy, Atopic Dermatitis, and Allergic Mechanisms Section. He was the lead NIAID scientist behind the paradigm-shifting LEAP trial, which demonstrated that the development of peanut allergy could be prevented in children at high risk by the early introduction of peanut-containing food. In recognition of his lifetime of national service to allergy research and patient care, Dr. Plaut received the 2018 American Academy of Allergy, Asthma, and Immunology Special Recognition Award.

Tributes and Awards

Dr. Fauci paid tribute to Dr. Adel Mahmoud, an esteemed colleague, who passed away in June. He recognized Dr. Mahmoud’s many accomplishments, which include overseeing the creation and marketing of four important vaccines against rotavirus, HPV, shingles, and MMRV, and helping develop the Global Health Program at Princeton.

NIAID received a U.S. Patent and Trademark Office 2018 Patent for Humanity Award for creating a low-cost temperature tolerant rotavirus vaccine for use in developing countries. The award recognizes Dr. Albert Kapikian, formerly with NIAID’s Laboratory of Infectious Diseases, for his lifelong contributions to developing rotavirus vaccines.

Meetings and Events

On June 5, Dr. Fauci participated in a panel discussion of the future of U.S. leadership and global health and development hosted by the National Academy of Medicine.

On June 12, CDC Director Dr. Robert Redfield visited NIH and met with senior leadership to discuss research on opioids, the BRAIN Initiative and neuroscience, and efforts to develop a universal influenza vaccine. He toured both the NIAID Special Clinical Studies Unit and Vaccine Research Center.

In mid-July, Dr. Fauci spoke at a National Press Club luncheon, where his remarks were largely focused on influenza and efforts to develop a universal influenza vaccine.

On September 6, HHS Deputy Secretary Eric Hargan, Dr. Fauci, and others visited the NIAID Biovisualization Lab. Dr. Fauci and the NIAID BioIT team explained how scientists are using virtual reality to view and interact with virus proteins in 3D, which is aiding efforts to develop a universal influenza vaccine as well as other viral vaccines.

Budget Update

The FY 2019 President’s Budget Request released on February 12, 2018, included an overall funding decrease to NIH of 4.8 percent or $2.5 billion below the FY 2018 operating level.

On September 13, the joint Senate and House Conference Committee approved a bill that provided NIH an increase of 5.4 percent or $2 billion more than the FY 2018 operating budget. NIAID received a 4.7 percent increase, which included an additional $37 million earmarked for antimicrobial resistance research and $40 million earmarked for research on a universal influenza vaccine. If both chambers of Congress and the President pass the bill into law before the end of FY 2018, we will have a spending bill before the beginning of FY 2019. Dr. Fauci noted that if this happens, it would be the first time in 22 years that we have had a bill in time for the new fiscal year.

Dr. Fauci summarized NIAID’s FY 2019 interim financial management plan if we start the fiscal year under a continuing resolution. Taking 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 20 percent from their planned budget level. Our estimated success rates for research project grants will be between 19 and 22 percent.

Legislative Update

On June 6, Dr. Fauci spoke at the New Hampshire Business Day, a day-long congressional event for members of the state’s business community. The event was hosted by Senator Jeanne Shaheen, a member of the Senate Appropriations Committee, and provided Dr. Fauci the opportunity to discuss research to develop a universal influenza vaccine and other NIAID high priorities.

On June 15, Dr. Fauci testified before the House Energy and Commerce Subcommittee on Oversight and Investigations on U.S. public health preparedness and response to biological attacks, pandemics, and emerging infectious disease outbreaks.

Representative Ro Khanna visited NIH on July 30 to discuss NIAID research on food allergy. He met with Dr. Fauci and Dr. Daniel Rotrosen, director of DAIT. Later that day, Senator Tom Udall, a member of the Senate Appropriations Committee, also visited NIH to discuss research on the human microbiome.

On August 23, Dr. Fauci accompanied NIH Director Dr. Francis Collins as he testified before the Senate Committee on Health, Education, Labor and Pensions at a hearing on Prioritizing Cures: Science and Stewardship at the NIH. Dr. Fauci updated the Committee on implementing our strategic plan for a universal influenza vaccine.

On September 14, Dr. Fauci briefed the Congressional Black Caucus Foundation about how evidence-based tools for HIV prevention and treatment can help end stigma surrounding HIV/AIDS.

Other Information Items

Dr. Fauci began by citing statistics from the UNAIDS Global AIDS Update from July 2018. Since the start of the pandemic, 77 million people have been infected with HIV, and there have been 35 million deaths. He presented selected accomplishments of the President’s Emergency Plan for AIDS Relief (PEPFAR), which is celebrating its 15th anniversary—14 million people have received antiretroviral therapy, 2.2 million babies have been born HIV-free to HIV-positive women, more than 85 million people received HIV testing services, and care has been provided for over six million orphans, vulnerable children, and their caregivers.

Dr. Fauci noted that he gave a keynote address on the Durable Control of HIV Infection in the Absence of Antiretroviral Therapy at the International AIDS Conference that was held in Amsterdam in July. He summarized results from several studies that show there is no evidence that people who have successfully achieved and maintained viral suppression through antiretroviral therapy transmit the virus sexually to their HIV-uninfected partners.

He continued with an update on the Ebola outbreak in the Democratic Republic of the Congo. An outbreak in the western part of the country that began in December 2017 was declared over in July. A week and a half after it was declared over, a second outbreak occurred in the eastern part of the country at the border of Uganda and Rwanda. Dr. Fauci outlined the multiple interventions being administered to control the second outbreak. He noted that Dr. Cliff Lane, NIAID deputy director of Clinical Research and Special Projects, was en route to the Democratic Republic of the Congo to help organize a controlled trial.

Dr. Fauci concluded by giving brief updates on influenza, tuberculosis, tick-borne diseases, Zika, and smallpox.

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

Dr. Holland began by giving an overview of the Division of Intramural Research’s (DIR) activities over the last year, which include 819 publications and 183 active clinical trials on site at NIH and at selected international sites.

He presented DIR’s priorities, which are:

  • Transformative medicine and biomedical research
  • Bench-to-bedside research taking advantage of NIH’s Clinical Center, as well as domestic and international clinical sites
  • Responding to public health threats, including drug-resistant microbes and emerging viruses
  • Partnering to advance vaccines, therapeutics, and diagnostics for infectious and immunologic diseases

Dr. Holland mentioned DIR leadership changes that have occurred over the last year, along with personnel changes, including recent departures, new hires, recently tenured investigators, and new tenure-track investigators.

Over the last couple of years, DIR established the Rocky Mountain-Bethesda Program to increase interaction and collaboration between the two locations. DIR funds the Program, which is designed to have one student assigned to dual mentors and dual labs. The Program is in its second iteration.

Dr. Holland highlighted some of DIR’s scientific research areas, including SHIV, respiratory syncytial virus, inflammatory bowel disease, atopic dermatitis, and Zika.

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

Director’s Report

Dr. Rotrosen presented the following scientific and Division activities:

Staff and Organizational Changes

Marshall Plaut, M.D., retired after 27 years of dedicated and distinguished service as the chief of the Allergic Mechanisms Section, Division of Allergy, Immunology, and Transplantation. As the NIAID and NIH expert on food allergy, Dr. Plaut was instrumental in leading clinical research to develop treatment and prevention strategies for food allergy. We wish him the best in his well-deserved retirement.

Ousmane Toure, PharmD, MSc, Ph.D., joined the Clinical Research Operations Program as a pharmacist in August 2018. Dr. Toure received a PharmD from the University of Mali in Marseille and an MSc in Applied Microbiology from the University of Quebec in Montreal. After completing a Ph.D. in Microbiology and Molecular Genetics from Howard University in Washington, DC, he spent 10 years at the National Cancer Institute as a geneticist and research coordinator researching cancer genetics. After the NIH, Dr. Toure practiced pharmacy at several locations, culminating in serving as a pharmacist at NATO’s Supreme Headquarters Allied Powers Europe (SHAPE) in Belgium.

Selected Funding Opportunities

NIH
The INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) project:
(NOT-OD-18-194 and NOT-OD-18-195). This project proposes to study individuals with Down syndrome to improve their health and well-being, and to learn about their risk and resilience factors for common diseases. The INCLUDE project will focus on commonly occurring conditions in individuals with Down syndrome that are also seen in the general population, such as Alzheimer’s disease/dementia, autism, cataracts, celiac disease, congenital heart disease, immune system dysregulation, and diabetes. Information learned by studying people with Down syndrome will also help us learn about these conditions in people without Down syndrome. Conversely, people with Down syndrome infrequently develop solid tumors such as breast or prostate cancer, and, despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, they rarely develop atherosclerosis or have myocardial infarctions.

Division Activities

Allergy, Asthma, and Airway Biology Branch

IgE-Mediated Meat Allergy Workshop. On June 11, 2018, NIAID organized a workshop in Rockville, Maryland, to discuss the current understanding on the causes of IgE-Mediated Meat Allergy and the current management of this disease, and to identify research gaps that are critical to further advancements in diagnosis, prevention, and treatment. International experts presented research on the disease and discussed future directions. A manuscript to summarize the conclusions of the workshop is planned.

Asthma and Allergic Diseases Cooperative Research Centers: Advances in Asthma. On May 20, 2018, NIAID organized a symposium as part of the Annual American Thoracic Society (ATS) Conference in San Diego, California. Experts in the field presented lectures on topics including epithelial cytokines and airway inflammation, airway epithelial reprogramming in asthma, chromosome 17q21 genes and airway remodeling in asthma, and surfactant protein A as an innate immune modulator in asthma.

What Factors Determine Asthma Severity? Lessons from the NIH Inner City Asthma Consortium. On May 20, 2018, NIAID organized a symposium as part of the Annual American Thoracic Society (ATS) Conference in San Diego, California. Experts in the field presented lectures on topics including phenotypes of airflow obstruction in asthma and implications in disease severity, the effect of rhinitis on asthma severity, and childhood asthma phenotypes associated with disease severity.

Tracking T and B Lymphocytes in Allergic Diseases: State-of-the-Art. On May 28, 2018, NIAID organized a workshop as part of the annual meeting of the European Academy of Allergy and Clinical Immunology (EAACI) in Munich, Germany. Experts in the field presented lectures on topics including monitoring allergen-specific T cell responses in patients receiving immunotherapy, heterogeneity of food-specific T cells and relationships to clinical phenotypes, and analysis of B cell repertoires in peripheral blood and gastrointestinal tissues in peanut allergy.

Basic Immunology Branch

Modeling Immunity for Biodefense. On June 5, 2018, the annual meeting for the Modeling Immunity for Biodefense (MIB) program was held in Rockville, Maryland. The overall goal of the MIB program is to build computational models of immunology to better understand and study the immune response to infection or vaccination. The four awarded U19 centers are using influenza infection and/or vaccination as their infection/vaccination model. The annual meeting facilitates communication and collaboration among the four supported U19 centers. During the meeting investigators presented recent results and plans for the coming year. The scientific meeting was followed by a brief Steering Committee meeting, comprised of the principal investigators and NIAID staff, to discuss integration between centers, feedback of the external scientific advisory group, the Infrastructure and Opportunity Fund (IOF) projects, and output from the Centers.

B Cell Epitope and Mechanisms of Antibody Protection, Large Scale T Cell Epitope Discovery, and Immune Epitope Database and Analysis Resource Annual Progress Meeting. On June 20 and 21, 2018, the annual meeting of the B Cell and T Cell Epitope Discovery Programs and the Immune Epitope Database and Analysis Resource (IEDB) was held in Rockville, Maryland. During the meeting investigators provided updates from the both the B Cell Epitope Discovery and IEDB programs. 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.

Caveats of the Mouse Model: Parameters that Affect Immunology Research for Vector-Borne Pathogens. On August 23 and 24, 2018, DAIT and DMID jointly hosted a workshop in Rockville, Maryland, to explore various factors that impact immune responses of laboratory mice and how they negatively impact the usefulness of the mouse model for studying immunity to microbes, particularly vector-borne pathogens. These factors include genetic as well as environmental parameters. Such parameters result from standard animal housing procedures, which significantly impact the animals’ immune status. Workshop participants, which included principal investigators from different research areas and animal facility managers, were tasked with proposing realistic approaches for addressing the factors that affect immune responses of laboratory mice.

Autoimmunity and Mucosal Immunology Branch

Primary Immune Deficiency Treatment Consortium (PIDTC). From May 9 to 11, 2018, the 8th Annual Scientific Meeting of the Primary Immune Deficiency Treatment Consortium (PIDTC), including the 4th Annual Education Day, was held in Philadelphia, Pennsylvania. The consortium of over 40 North American centers was established with the goal of building collaborations to improve outcomes for primary immune deficiency (PID) patients who receive hematopoietic cell transplantation (HCT) or other forms of treatment. Presentations included updates of observational protocols of the consortium in severe combined immune deficiency (SCID), chronic granulomatous diseases (CGD), and Wiskott-Aldrich syndrome (WAS); a session chaired by the Patient Advocacy Groups; and 19 cases presented by young investigators.

Cooperative Study Group for Autoimmune Disease Prevention. On May 11, 2018, the annual meeting for the CSGADP was held in Rockville, Maryland. The mission of this program is to engage in scientific discovery that significantly advances knowledge for the prevention and regulation of autoimmune disease. Principal investigators from the group presented recent highlights from their projects in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. The group also heard and discussed reports from outside investigators who were awarded funding from the CSGADP for pilot studies in autoimmune disease prevention.

Mucosal Immunology Studies Team (MIST). On May 31 and June 1, 2018, MIST held its annual meeting in San Diego, California. MIST is comprised of 14 U01 cooperative agreement awardees, and its goal is to discover and define novel basic immune mechanisms, cells, mediators, and pathways operating at the mucosal surface; to explore innovative hypotheses; and to address difficult unsolved questions in mucosal immunity. The meeting brought together committee members to review progress on all projects, to facilitate development of new collaborations and sharing of newly developed tools, and to provide constructive advice on ongoing projects. The committee discussed how recent scientific breakthroughs could be exploited to advance understanding of mucosal immunology.

At Crossroads of Autoimmunity and Primary Immunodeficiency. On June 20, 2018, DAIT sponsored a symposium at the 2018 annual Federation of Clinical Immunology Societies (FOCIS) meeting in San Francisco, California. The goal of this session was to explore the association of immunodeficiency diseases and autoimmunity and open new avenues for personalized therapies for autoimmune diseases (syndromes).

NIH Grant Applications: A Look at Your Summary Statement. On June 22, 2018, DAIT program staff, in collaboration with staff from NIAID’s Scientific Review Program, held the latest in a series of workshops at the FOCIS annual meeting in San Francisco, California. This workshop focused on how to read a summary statement and how to productively discuss it with a program officer.

Radiation and Nuclear Countermeasures Program (RNCP)

Trans-NIH Workshop on Generative Ideas in Geroscience. On May 14, 2018, NIAID, in collaboration with NIA, NIEHS, NINR, NIDCR and NEI, organized a workshop in Rockville, Maryland. The goal was to discuss the impact of aging in strategies to mitigate disease conditions and the changing response to adverse events due to age. The meeting included a variety of invited speakers as well as leading regulatory experts and was attended by researchers, program officers from different institutes and centers, industry, and academia. A meeting report on this workshop is currently being generated for publication in GeroScience.

Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency. On August 30, 2018, the RNCP and the Radiation Injury Treatment Network co-sponsored a meeting in Rockville, Maryland. The goal of the meeting was to discuss trends in clinical practice utilizing licensed (or in clinical trials) growth factors and other cytokines; as well as preclinical research approaches under consideration and their applicability to a mass casualty response. Recommendations for future research, and development of improved response guidelines were drafted. Attendees included staff from government planning and funding agencies, healthcare providers, hospital-based emergency management, and pharmDs interested in disaster planning and industry and academic researchers engaged in preclinical development of candidate growth factors. A manuscript detailing the content of the presentations and outlining the recommendations from the breakout groups is in preparation.

Concepts Presented for Clearance

FY 2020 Research Concept Clearances

Fc-Dependent Mechanisms of Antibody-Mediated Killing (U01)
This initiative will expand understanding of ADCC and ADP mechanisms of action. The supported studied are expected to generate foundational data and tools that can be applied to the prediction of Fc-mediated killing activity by antibodies.

The Subcommittee endorsed and unanimously approved this initiative.

Fc-Dependent Mechanisms of Antibody-Mediated Killing (R21)
This initiative is expected to generate preliminary data, reagents, and tools to inform prediction of Fc-mediated killing activity by antibodies. Such data should accelerate development of therapeutic monoclonal antibodies and design of vaccines or vaccine-adjuvant combinations that induce antibody responses capable of killing infected host cells, particularly in cases where induction of neutralizing antibodies fails or is insufficient for clearance of infection.

The Subcommittee endorsed and unanimously approved this initiative.

Processing and Presentation of Non-Conventional MHC Ligands (R21) (R01)
The objective of this program announcement is to understand the antigen processing and presentation mechanisms used in the generation of novel peptide products and the contribution of these unique antigenic products to protective immune responses against infectious pathogens, in response to vaccines, or in the induction or progression of immune-mediated diseases.

The Subcommittee endorsed and unanimously approved this initiative.

Computational Models in Immunity (U01)
This program will support the development, refinement, and validation of computational models of the immune system through iterative immunological experimentation and computational modeling. It will also support pilot projects, summer schools, and symposia to make computational modeling more accessible to the broader research community.

The Subcommittee endorsed and unanimously approved this initiative.

Molecular and Genetic Characterization of Inborn Errors of Immunity (R01) (R21)
The purpose of this initiative is to advance the experimental validation and functional characterization of genetic variants in coding or non-coding genomic regions that result in inborn errors of immunity/primary immunodeficiency diseases and to elucidate the molecular, cellular, and immunological mechanisms of these disorders.

The Subcommittee endorsed and unanimously approved this initiative.

Development of Radiation/Nuclear Medical Countermeasures (MCMs)
This initiative will address gaps and accelerate the research and development of MCMs against acute and delayed radiation syndromes.

The Subcommittee endorsed and unanimously approved this initiative.

V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., director, DMID

Director’s Report

Dr. Emily Erbelding, director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on September 17, 2018. Dr. Erbelding reported on recent personnel changes across the Division, and introduced several new staff members (Enteric and Sexually Transmitted Diseases program: Lori Newman and Leah Vincent; Bacteriology and Mycology program: Erica Raterman; Office of Biodefense Research Resources and Translational Research (OBRRTR): Rick Sciotti; Virology program: Jean Patterson; and Respiratory Diseases program: Brooke Bozick) and new appointments of existing personnel (OBRRTR: Judy Hewitt, deputy director; Respiratory Diseases: Karen Lacourciere, acting section chief for TB, Leprosy, and Mycobacterial Diseases).

Dr. Erbelding reported on several recent DMID scientific developments, including the FDA approval of a small molecule drug, TPOXX (tecovirimat or ST-246), to treat smallpox infections. NIAID supported the early development of this product starting in 2003, and it was eventually transitioned to BARDA for further development. Dr. Erbelding also reported on another product that was recently approved by the FDA, eravacycline, a novel synthetic tetracycline for the treatment of complicated intra-abdominal infections. NIAID supported the discovery and early preclinical development of this product over several years. Dr. Erbelding also noted that FDA recently approved two formulations of tafenoquine for two different malaria indications. NIAID played a role in the early development of this drug, which was discovered by the Walter Reed Army Institute of Research (WRAIR). NIAID provided preclinical and clinical support.

In addition, Dr. Erbelding provided an update on efforts related to NIAID’s Universal Influenza Vaccine Strategic Plan and reported that DMID was moving rapidly to execute activities responsive to all aspects of the plan. Specifically, she noted the release of the Collaborative Influenza Vaccine Innovation Centers contract solicitation to develop promising universal influenza vaccine candidates.

Program Updates

Update on NIAID Emerging Infectious Diseases Preparedness Activities – Dr. Cristina Cassetti, chief, Virology Branch

Dr. Cassetti described ongoing NIAID activities related to infectious diseases outbreak preparedness. Briefly, Dr. Cassetti described efforts across the Institute, involving both the intramural and extramural programs, to evaluate lessons learned from recent outbreaks (Ebola and Zika) and prepare for the next outbreak. Dr. Cassetti described key aspects of current preparedness activities, which fall into distinct categories: 1) strategic efforts, focused on building and enhancing collaborations with U.S. and global partners, and creating and maintaining searchable databases of expertise to help the research response in the event of a new infectious disease outbreak; 2) logistical efforts, including the development of an internal SOP for emergency outbreak response that delineates the roles, responsibilities, and procedures for NIAID staff; 3) funding approaches, including the new NIH Urgent Competitive Revision to Existing NIH Grants and Cooperative Agreements funding opportunity announcement (PA-18-935) and the use of broad agency announcements to quickly solicit needed research; and 4) efforts of an NIAID Preparedness Working Group to identify knowledge gaps within viral pathogen families that would delay a research response and leverage existing resources and develop new research activities as needed.

Concepts Presented for Clearance

The following FY 2020 concepts were presented to the Subcommittee:

Emerging Infectious Disease Research Centers and Emerging Infectious Disease Research Centers Coordination Center (Note: these concepts are closely aligned and were described in a single presentation).
The Emerging Infectious Disease Research Centers (EIDRCs) will comprise a coordinated network of research centers in regions around the globe where emerging and re-emerging infectious disease outbreaks are likely to occur. Multidisciplinary teams of investigators will study pathogen/host surveillance and prevalence, pathogen transmission, pathogenesis and immunologic responses in the host, and will develop reagents and diagnostic assays for improved detection for important emerging pathogens and their vectors. The related Coordination Center would coordinate select aspects of each EIDRC’s research project(s) involving data management, sample collection and storage, sharing of reagents and diagnostics, and will ensure collaboration among and between the Centers.

The Subcommittee members were in agreement that the establishment of such a network along with a separate Coordination Center was important and timely. Several Subcommittee members suggested that critical to this effort will be the need to tap into existing infrastructure and expertise, including platforms to address sample sharing across international borders and veterinarians. Program staff was appreciative of the specific suggestions and will consider these points as the initiative is developed. Furthermore, Subcommittee members noted and staff agreed that junior foreign investigators should be eligible for pilot research project awards. A similar concern mentioned by all the reviewers related to the need to coordinate this effort with other related programs in order to avoid duplication, a role that could be assumed by the Coordination Center. The Subcommittee members also noted that the current level of funding proposed may be inconsistent with the plethora of activities proposed and encouraged DMID to consider this further. The concept was unanimously approved.

Targeted Prevention for Tick-borne Diseases
This initiative would support the development of prevention approaches for tick-borne diseases such as identification and testing of antigens for human vaccines against tick-borne pathogens or modification/improvement of candidate vaccines. Overall, the Subcommittee was highly supportive of this initiative as effective treatments do not exist for many endemic tick-borne diseases, especially the tick-borne viruses. The need to include multiple, relevant tick-borne pathogens in this initiative was stressed. A few members discussed the possibility of using the cooperative agreement mechanism in order to foster collaborations among investigators and to increase programmatic involvement in ongoing research. One member pointed out that cooperative agreements could also potentially allow for cross-pollination of the tick-borne diseases field and the tropical medicine arena. The Subcommittee also noted that, given the history of the human vaccine for Lyme disease, which is no longer available, it is critical that the scientific community communicate appropriately and effectively with the public regarding prevention approaches for tick-borne diseases. The concept was unanimously approved.

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

Dr. Dieffenbach thanked four committee members, Amanda Castel, John Guatelli, Scott Hammer and Sharon Hillier, who are rotating off the committee and welcomed Adriana Andrade, M.D., as the new chief of the HIV Research Branch in the Therapeutics Research Program of DAIDS.

Budget Update

The FY 2019 President’s Budget Request was released on February 12, 2018 and called for a fairly significant cut to NIH. On September 13, a conference committee of the House and Senate was convened and moved forward with a budget that includes an approximate 4.7 percent increase to NIAID, with an overall $2 billion increase to NIH. It was highlighted that while the overall number for NIH has increased, the AIDS budget has not received an increase for another year in a row. Therefore, cost sharing approaches are being discussed with the Office of AIDS Research (OAR). Until a budget is passed, there most likely will be a continuing resolution to begin FY 2019. This means beginning with a conservative start to the year. The interim financial plan has the R01 payline starting at the 10th percentile and will go up to 12 should there be a budget, and competing research initiatives will be cut up to 20 percent.

Q: Has there always been 4 percent difference between established and new PIs?
A: Yes. We are trying to get the same success rate for new PIs and established PIs. Right now, the forecast is it would be approximately 4 percent.

Q: When you say there is a 20 percent in competing research initiatives, are these to new initiatives?
A: We start by building in a 20 percent cut during the planning process for initiatives. This cut is already built into the 2019 budget. Some money will flow back once there is a budget. The cut is not in solicited not unsolicited grants but is done through the RFA and contracts.

Scientific Updates

SEARCH Approach - The SEARCH Approach involved a partnership of UCSF with PEPFAR and the community for a multi-disease, patient-centered approach to HIV care – “test and treat” – that is a “patient-centered” approach to care delivery. After three years of interventions, the SEARCH Approach found that there was a 20 percent reduction in terms of mortality for HIV as well as a reduction in incidents of TB and a fairly significant impact on hypertension and diabetes. Economic factors were built in and found an average increase of 4.4 hours of additional working hours per week for each HIV positive adult enrolled in the intervention arm. Summaries of HIV Test and Treat coverage, and HIV Incidence were also discussed. Concluding thoughts were that while SEARCH reduced mortality and TB, work toward HIV elimination is not done. This trial showed that Treatment as Prevention (TasP) is an important tool to reduce incidence but may not be sufficient to establish epidemic control. PrEP and other strategies are still needed until a safe, effective, and durable vaccine is available.

U=U Study (Undetectable = Untransmittable) - In Amsterdam at the 22nd International AIDS Conference, the PARTNERS 2 study was presented, which provided data in support for U=U. The background for PARTNERS 2 was based on the HPTN 052 study which demonstrated no linked transmissions within the study involving condomless sex acts but only involved heterosexual couples. Data on 35,000 MSM couples was accumulated through Opposites Attract study and the PARTNER 1 study and showed no linked transmissions. The PARTNER 2 study built on these previous studies and enrolled an additional 450 HIV-serodiscordant MSM couples. The strict study guidelines and procedures were listed which involved condomless sex, no reported or allowed PrEP or PEP use, a specific plasma HIV-1 RNA load of <200 copies/mL which is higher than the 20-50 copies/mL typically used by others. Investigators reported the rate of within-couple phylogenetically linked transmissions and showed that new infections were not linked to the initially positive partner’s virus. These results reinforced the point of Undetectable = Untransmittable (U=U) – the risk of HIV transmission when HIV viral load is suppressed is effectively zero. The CDC “Dear Colleague” letter from 2017 that continues to maintain that people taking ART daily and achieve and maintain undetectable viral load effectively have a no risk of sexual transmitting the virus to an HIV negative partner still holds and will continue to hold. This emphasizes why support for treatment as prevention as part of public health is still needed as a tool to help end the epidemic.

Tsepamo Study - The Tsepamo study’s primary aims are to evaluate adverse birth outcomes by HIV-status and ART regimen, determine if there is an increased risk of neural tube defects (NTDs) among infants exposed to efavirenz (RFV) from conception, and after the roll out of Dolutegravir/Tenofovir/Emtricitabine (DTG/TDF/FTC) by Botswana, the analysis plan was updated to include omen exposed to ART combination. Data from key observations, results were summarized and discussed, and investigators had concluded that there was a concerning early signal for DTG and NTDs that require further data. An alternate explanation had not been identified within the Tsepamo data. As these were interim results, the study will continue for a further nine months for ongoing surveillance to determine if the projected NTDs will occur. The steps DAIDS has taken regarding DTG use were listed and included having contacted network leadership and study teams requesting a pause on studies that administered DTG (and CAB) and provided guidance to inform site PIs and participants of the new safety concern, informed participants of right to continue or discontinue participation, updated informed consent to include the safety concern, and reconsented all participants. At this time, all studies will continue under the new set of recommendations, and DAIDS will continue to monitor these DTG issues.

NIAID HIV/AIDS Clinical Trials Network Recompetition: Draft Timelines

DAIDS is on schedule to publish the funding opportunity announcements (FOAs) with the FOAs for leadership, Safety and Data Monitoring Center and lab scheduled to be published in January with a receipt date in September. The Clinical Trial Units (CTUs) FOAs are off cycle by design so that there is an opportunity for the scientific agenda to be set and then get incorporated into the CTU. Award dates in early FY 2021, December 2020, are still on schedule.

Office of AIDS Research Advisory Committee (OARAC) Update
Richard Chaisson, M.D.

Dr. Chaisson presented highlights of the OARAC meeting on July 12, 2018. Charles Wire, Ph.D., was announced as the new OARAC chair and a request for applications (RFA) had been issued for the rebuilding of the Caribbean Primate Research Center, which was destroyed in Hurricane Maria last year. The Trans-NIH HIV/AIDS Professional Judgment Budget was submitted by OAR to the President requesting a 15 percent increase to NIH AIDS funding. The Trans-NIH Strategic Plan for the current 2019 and 2020 two-year cycle is out and a multi-year strategic plan for FY 2021 and following years is underway. A cost-sharing overview was given which emphasized that it is a high priority for the OAR to leverage what HIV has to offer to other areas of science and what other areas of science have to offer to HIV, and how they can be mutually beneficial. Currently there is a cost-sharing pilot project out, an RFA from the National Institute of Aging for pathogenesis of AIDS-related HIV neurodegeneration. Funding was to be a 50/50 split of HIV funds and Alzheimer’s disease and related dementia funds. The Antiretroviral (ART) Guidelines Committee met and issued a response within weeks of the news from the Botswana study with Dolutegravir about the neural tube defect finding. From this, the ART Guidelines report was generated which revealed their response to the WHO and Harvard report on DTG and new revisions are being incorporated into the guidelines. Adult OI guidelines covering the areas of herpes, HBV, TB, and immunizations scheduling are also undergoing revisions.

Q: Based on the information we now have on U=U, is there any discussion on changing Guidelines recommendations for women who are infected and breastfeeding in the U.S.?
A: We don’t have data on breast-feeding data currently and we are currently trying to accumulate it, but this is an area of ongoing emphasis.

AIDS Vaccine Research Subcommittee (AVRS) Update
James Bradac, Ph.D.

Dr. Bradac presented a summary of the AIDS Vaccine Research Subcommittee that was held on June 5 and 6. Two most recent new AVRS members were introduced. The meeting included the Bonnie Mathieson memorial symposium on the first day and then a half day programmatic update from the three Vaccine Research Program branch chiefs. The Preclinical AIDS Vaccine Research update summarized the vaccine research programs, HIVRAD and Innovation Grant Program, awards from FY 2018 and the funding plans for FY 2019, including making an award for consortia for HIV/AIDS vaccine development (CHAVD) which will replace CHAVI-ID. CHAVD was approved at ARAC in September 2017 and applications are under review. Current areas of vaccine research emphasis are broadly neutralizing antibodies (bNAbs), Fc-mediated protection, and protection via CD8+ cells and for CHAVD, the research will be concentrated on protection via bNAbs and Fc-mediated protection. The rationale for choosing a bNAb focus involved preclinical nonhuman primate studies showing how they protect against SHIV infection. Many bNAbs to HIV have been developed or isolated which has enabled the identification of epitope targets on the HIV envelope. Researchers are also targeting unmutated common ancestors of bNAbs, then boosting and maturing these Abs. Targeting germlines as a strategy for inducing bNAbs was also described. A table was shown of current research programs summarizing the PIs and their projects involving germline targeting immunogens for induction of bNAbs. This table also showed funding source, epitope, Ab affinity, and trial status. It was noted that an in-depth analysis of the study individuals, e.g., lymph node biopsies or gene activation analyses, will be necessary to do these clinical trials. Simply measuring neutralizing antibodies in the sera may not be enough as in most cases neutralizing antibodies are not expected to be made with these particular vaccines. A timeline of trials from the clinical program listed 30 trials and their current stage and whether they are efficacy trials or are earlier stage trials. About six of the earlier stage trials are related to RV144 and seven other earlier stage trials are related to antibody-mediated protection. Four efficacy trials, HVTN 702, HVTN 705, and the AMP studies (HVTN 703 and 704) were further described. HVTN 702 is the follow-up trial of HVTN 100, the RV144 trial, with the hope of increasing the duration of protection by both using an improved adjuvant M59 and doubling the number of boosts. Dr. Bradac concluded by presenting the overall AVRS recommendations for the preclinical, translational, and clinical areas. The next AVRS meeting will be January 29 and 30, 2019.

Q: Are the immunogens that have the low affinity for the germline actually germline targeted, or are they just gp120s?
A: They are germline B-cell receptor targeting. Investigators are also thinking about the boost that you might use; several boost-type immunogens have been developed, manufactured, and vialed. Also, most HIV envelopes that are isolated do not bind at the germline. The hope is to develop vaccines that will target the germline.

Concepts Presented for Clearance

Prevention Sciences Program (PSP)

Long-Acting Drug Delivery Systems for ART Optimization in HIV-1 Infected Children
Patrick Jean-Philippe, M.D.

The objective of this initiative is to accelerate development of safe and effective long-acting drug delivery systems (LA-DDS) for improved, simplified treatment of HIV-1 in children. This is a new initiative with a duration of five years. It is estimated that there will be three to five awards and the first-year total cost for the initiative is $3.86 million. This initiative invites applicants engaged in the development of existing LA-DDS platforms at early product development stages to perform specific preclinical activities that enable product optimization and accelerates translation to HIV-1 infected children. It is estimated as of 2017 that there were 1.8 million children living with HIV, that there were 180,000 new HIV infections, and there were 110,000 AIDS-related deaths. The limitations of currently available ART regimen in children were shown and included suboptimal viral suppression, pretreatment drug resistance, ontogeny of drug metabolizing enzymes and transporters in young children, toxicity/side effects, poor palatability/suboptimal formulations, adherence concerns, and stigma. Also shown were pediatric drug development challenges - pediatric ARV development often lags significantly behind development in adults; generation of preclinical data relevant to inform pediatric studies seldom occurs early in drug development; PSP/PIP not required until end of Phase II or in some cases Phase I; traditional approach to studies serially from older to younger age groups causes further delays; late age-appropriate formulation development further delays study initiation in younger age groups; and supporting optimization and evaluation of LA-DDS formulations in suitable preclinical animal models could accelerate testing in pediatric populations. Emerging data from studies and focus group discussions on LA-DDS indicates the prospect of increased acceptability in adults and found higher acceptability for long acting injectables over oral ART. Areas of research interest include a proposed LA-DDS with the incorporation and simultaneous delivery of a fully active ARV combination, minimum doing interval of four weeks or more, and administration strategies such as oral, implant, transdermal, nanoformulated injectable systems; an animal antiviral efficacy study of the LA-DDS candidate in the R33 phase in nonhuman primates; antiviral safety of the proposed products within the LA-DDS in animal models; pharmacokinetic studies in appropriate animal models with activities critical to characterizing the LA-DDS characteristics and capacity; and industry partnership and collaboration, which is a requirement. Enhanced targeting of anatomical compartments, early assessment of preferred user characteristics in end user population using established behavioral and social science tools, and Target Product Profile identifying product optimal and minimally acceptable criteria is strongly encouraged but not required. Nonresponsive areas of research include de novo DDS/small molecule discovery work; cGMP manufacture activities; applications proposing development of LA-DDS with duration of action that do not meet the minimum duration defined in the FOA; intravenous infusion of any component of the LA-DDS; use of any live biotherapeutic or vector system to produce/deliver the anti-HIV component of the proposed drug product; development of broadly neutralizing antibodies; LA-DDS platforms that are in late phases of clinical testing or planned clinical testing in pediatric populations; and applications without an industry partner are nonresponsive and will not be reviewed. This initiative will use the Phased Innovation Awards (R61/R33) mechanism, which is milestone driven with phased research activities. Support for up to two years for the R61 phase to fund activities to optimize LA-DDS, and up to three years for the R33 phase to fund preclinical activities of the optimized LA-DDS formulation. The concept was reviewed by ARAC members and their questions, comments, and question responses were summarized. The committee members were asked to cast their votes electronically.

Q: Regarding use of baby monkeys compared with juvenile monkeys, what is the feasibility of using smaller sized monkeys when you are limited to the amount of samples you can get?
A: This becomes a peer review issue and the applicant will have to propose a model and then defend the choice of the model.

Q: What is the issue in translating from an adult situation to a pediatric? Why have a separate development track for a pediatric long-acting drug as opposed to trying it in adults first?
A: It is going to be tried in adults first. But we are trying to speed up the process that can traditionally take 8 to 10 years. Drugs have to be proven safe in adults first, but thereafter we have no idea how an implant or injected drug would behave in a pediatric subject. There are some significant research challenges in terms of changing physiology when you move down in size with the heart rate and metabolism. A small focused RFA like this is possibly the best approach to addressing these issues.

Ballot Voting Outcome
10 Approval
0   Approval with modification(s)
0   Deferral for further information
1   Disapproval

Advancing Biomarker Discovery and Novel Point-of-Care Diagnostics for Active TB Disease Detection in HIV-1 Infected and Exposed Children
Patrick Jean-Philippe, M.D.

The purpose of this initiative is to advance non-sputum-based TB diagnostics in HIV-1 infected and exposed uninfected children by promoting discovery and validation of novel TB biomarkers or development/optimization and early validation of novel TB diagnostic technologies for improved, simplified, rapid, and decentralized diagnosis of TB disease in these populations. This is a new initiative with a duration of five years. It is estimated that there will be three or four awards and the first-year total cost for the initiative is $3.08 million. WHO global statistics of TB burden and mortality in children was presented to show the considerable toll TB exacts in children. Younger children are especially vulnerable to TB and experience a high rate of progression to active disease upon exposure. In addition, recent meta-analysis estimates that the risk of TB disease in children with HIV was increased about eight-fold, increasing with degree of immunosuppression. TB diagnostic challenges in children include non-specific clinical manifestations and clinical course; paucibacillary disease; inability to expectorate; limited diagnostic sensitivity of current tests; and clinical algorithm/case definitions are insufficiently validated. The consequence of diagnostic challenges is that there is under diagnosis and under notification of cases. As TB mortality is often missed in global estimates of under-five mortality, there is urgent need for non-sputum-based, simple, accurate, point-of-care diagnostics for decentralized use in children. Research gaps for TB drug development of new TB diagnostics in children were overviewed along with the high priority target project profile for new TB diagnostics. Areas of interest are the target populations/age groups of HIV-infected or exposed young children who are less than five years old with diagnostic evaluation for TB disease in established prospective cohorts, or well characterized stored samples from such cohorts; eligible matrices that include serum, urine, stools, or other non-sputum matrices; proposed biomarker/diagnostic technologies that can be developed as point-of-care tools; and industry/diagnostic developer partnerships. Supported projects include activities aiming at new biomarker discovery on non-sputum-based matrices and early evaluation of their performance characteristics in well-characterized cohorts or biobanked samples from target population for detection of TB disease and development of innovative technologies into a novel prototype and early evaluation in well-characterized cohorts or biobanked samples for detection of TB disease. Nonresponsive areas of research include evaluation of sputum or other respiratory samples-based biomarkers or tests including molecular or microbiological/culture-based tests; initiation of late-phase prospective evaluation studies of TB diagnostics in children; validation of tests already approved/endorsed for use in that population; and cohorts/samples that do not predominantly include HIV-infected/exposed children and children less than five years. The relationship to other awards or programs was highlighted and then the program was reviewed by ARAC members and their questions, comments, and question responses were summarized. Committee members were then asked to cast their votes electronically.

Questions:

No questions

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

Therapeutic Research Program (TRP)

HIV/HBV Co-Infection: Research To Advance HBV Cure
Chris Lambros, Ph.D.

The purpose of this FY 2020 initiative is to conduct clinical, basic, and translational research to identify and address the challenges to achieve HBV cure. This is a new initiative with a duration of five years. It is estimated that there will be three to five awards and the first-year total cost for the initiative is $2.7 million. A background on hepatitis B (HBV) was given which summarized HBV as a global health problem with two billion people infected and over 880,000 annual deaths from HBV-related complications. There is a higher prevalence of HBV observed in people living with HIV; HIV accelerates the natural course of infection resulting in more rapid progression to cirrhosis and hepatocellular carcinoma. In addition, antiviral drugs can suppress viral replication and slow disease progression, but the treatment is not curative; HIV-infected individuals also have a much-reduced response to Engerix-B; and access to treatment is limited in low middle income countries. Hepatitis is a priority within the NIAID Strategic Plan of 2017 which aims to support research for infectious hepatitis as an HIV-associated infection by optimizing effect drugs that cure HBV in patients co-infected with HIV, developing improved diagnostics, noninvasive indicators of liver injury, and prognostic biomarkers for treatment outcome, and identifying pathways and mechanisms that accelerate the course of HBV liver disease in HIV co-infected individuals. There are several challenges for HBV cure attainment including that cccDNA remains permanently in infected hepatocytes; Direct Acting Anti-virals (DAA) only suppress viral replication and retard disease progression, however do not eliminate or silence cccDNA; current treatment endpoints do not consistently correlate with the presence of virus and degree of liver injury; insufficiently precise and correlative biomarkers and noninvasive diagnostic tools to access liver injury, treatment response, and the presence of residual virus; and incomplete understanding of the nature of the immune response in co-infected individuals and how this affects the natural history of HBV. This initiative will focus on three areas of research: immunology, virology, and therapeutics. Immunology will study the effect of HIV infection on the host ability to establish and sustain immune control of HBV infection by investigating how to stimulate HBV-specific innate immune response and how to restore HBV-specific adaptive immune response. Virology will explore basic mechanisms of HBV replication or HBV protein expression; elucidate the mechanisms responsible for cccDNA biogenesis, homeostasis, and decay; explore the influence of the host on the HBV life cycle; develop efficient cell culture models to enhance viral spread; and identify new viral targets and strategies to prevent drug resistance. The therapeutics area of research will develop reproducible cell-free test systems for high-throughput antiviral screening; develop small animal models that resemble HBV infection in humans; identify therapeutics with the potential to permanently silence or eliminate cccCDA; identify biomarkers and diagnostic tools with good prognostic value to enable easy translation into clinical care; and develop more reliable non-invasive clinical tools for assessing liver injury and stage of infection. The concept was reviewed by ARAC members and their questions, comments, and question responses were addressed and summarized. The committee members were asked to cast their votes electronically.

Q: How much of the funding will be from AIDS dollars versus the non-AIDS dollars?
A: It will be an appropriate blend of money from DMID to cover the things that are non-AIDS.

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

Programmatic Overview

Update on the Therapeutics Research Program (TRP)
Peter S. Kim, M.D.

The TRP leadership group and staff were briefly introduced and listed and the TRP mission, portfolio, and activities were presented. The Therapeutics Research Program’s mission is to improve the health of people living with HIV (PLWH) by developing therapeutics, diagnostics, and associated strategies to achieve durable viral suppression in all PLWH and addressing co-infections and co-morbidities that greatly impact the health of PLWH. TRP funds a broad portfolio of grants and contracts related to HIV diagnosis, treatment, cure, and related co-infections/co-morbidities, and activities are weighted towards clinical trials, including contracts to support clinical laboratories and the discovery and preclinical development of therapeutics.

The overarching goals and select research priorities for four disease categories were discussed:

HIV: Long-term goals for HIV include a functional cure for sustained ART-free remission; long-acting formulations and novel therapeutics for durable viral suppression; diagnostics for rapid point-of-care, home-based testing for viral load and drug resistance; and in partnership with the National Institute of Mental Health (NIMH) and other stakeholders, a large, broader strategy to combine biomedical treatment with behavioral and social interventions for increased uptake, durability, and effectiveness of treatment and strategies to overcome the impact of drug resistance at the individual and public health levels. More specific research priorities include attempting to engineer mAb to enhance their immune function, establishing optimal therapeutic combinations and testing novel immune-therapeutic strategies for a functional cure. Finally, TRP wants to invest in science that will help improve treatment outcomes with current technologies including point-of-care viral load and drug resistance, combination assays that can be used in the developing world, point-of-care and home-based assays for detection of viral rebound, biomarkers and assays for assessment of adherence, biomarkers for detection of HIV exposure and/or acute HIV infections, and in partnership with other stakeholders, develop tools that will enhance adherence and enable public health strategies to reduce the impact of drug resistance.

TB: As TB is the leading cause of morbidity and mortality among PLWH, the TRP is focused on improving the health of PLWH by improving health outcomes of those infected with TB. Long-term goals for TB encompass combination therapies for drug-sensitive and drug-resistance TB disease that require less than three months of treatment; chemo-prevention regimens that are less than two weeks; a vaccine to prevent progression of infection and reoccurrence after treatment for diseases; host-directed therapies that reduce the pulmonary damage that occurs as a result of diseases; and new biomarkers and diagnostics to allow better public health strategies and enable monitoring of treatment/prevention effectiveness. More specific research priorities include determining optimal combinations of new candidate drugs through the multiple phase II and III studies that are underway exploring novel combinations; understanding the immunopathogenesis of TB and mechanisms of bacterial persistence and drug tolerance; identifying and developing candidate therapeutic vaccines for latent and active TB; discovering and developing biomarkers for TB infection and disease, including extrapulmonary TB disease and drug resistance; and identifying strategies to effectively curtail TB transmission.

Hepatitis B and Hepatitis C: Hepatitis B and C are a significant cause of morbidity and mortality for PLWH, therefore TRP will collaborate with the Division of Microbiology and Infectious Diseases (DMID) to advance long-term goals that include curative treatments for HBV, non-invasive tools for monitoring treatment response, preventive HCV vaccine, long-acting HCV DAAs to enable public health treatment strategies, and point-of-care diagnostics to facilitate single site visit diagnosis and treatment initiation. Specific priorities for HBV include elucidating regulation of synthesis and epigenetic silencing for HBV cccDNA, biomarkers for non-invasive assessment of treatment response and liver disease, rapid, simple assays for diagnosis and treatment monitoring, and small animal models to reduce the cost of research. For HCV, specific priorities are in developing technologies to enable low- and middle-income settings with high HIV prevalence to benefit from advances for hepatitis C.

Other co-morbidities and co-infections: PLWH are more susceptible to non-infectious co-morbidities more often and earlier than people without HIV infection. Thus, TRP is working with stakeholders across NIH, as is evidenced by the REPRIEVE study in collaboration with the National Heart, Lung, and Blood Institute (NHLBI) and a recent workshop with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to explore obesity and fat metabolism in HIV-infected individuals. It is hoped that these types of partnership models with other stakeholders across the NIH will continue as there is a need to understand epidemiology and pathogenesis of immune dysfunction in the setting of viral suppression in order to develop effective treatment and prevention strategies for the various end organ diseases that are affected by HIV.

Q: Who decides if AIDS or non-AIDS money is used for a project that is basically an HBV or an HCV project where HBV/HCV is the more severe infection when someone is co-infected with HIV? Who makes the determination and are there guidelines?
A: There is a preliminary determination of what amount of money will be set aside by each party, but it can change depending on the specific application. If an application comes in that does not deal with HIV and only focuses on viral hepatitis, it will go to DMID. The determination is pre-set in referral guidelines, available publicly, that determine which applications go to DMID and which come to DAIDS.

Concepts Presented for Clearance

NIAID Office of Global Research (OGR)

U.S.-South Africa Program for Collaborative Biomedical Research-Phase 2
U.S.-Brazil Collaborative Biomedical Research

F. Gray Handley, M.S.P.H.

NIAID is involved with and committed to international collaboration of U.S. investigators who want to work internationally to answer questions surrounding infectious disease. Innovative international engagement is encouraged due to flat funding and resources because of the continued growth of the number of new diseases and the diseases that, as with TB, manifest outside the U.S. The two programs presented are within the larger context of international engagement and international initiatives and are supported by the NIAID vision for global research. Criteria for selecting co-funding partners includes untapped scientific opportunities, U.S. scientists’ interest and shared research priorities, willingness to share funding responsibility, adequately resourced research capacity, compatible research management, and shared outcome objectives. Currently, there are only five countries that meet these criteria and are in bilateral agreements. The process for bilateral scientific review and joint funding was schematically shown and the importance of clarity in the application was highlighted. The jointly funded collaborative biomedical research programs with Brazil and the Republic of South Africa (RSA) have the same objectives - to increase U.S. scientists’ access to research and research training opportunities in Brazil and RSA; initiate and/or strengthen long-term basic, clinical, and translational research collaboration; complement NIH funding with foreign counterpart funding; stimulate improved research infrastructure and research management capacity in Brazil and RSA; and expand the focus on NIH and U.S. scientist-identified priorities in Brazil and RSA.

The Brazil program was originally cleared five years ago, and a one-year pilot program was run with funding from the Brazilian Ministry of Health and Ministry of Science, Technology, Innovation, and Communications and NIH. There were 19 supplement awards that led to 17 publications, 3 presentations, and 11 graduate students supported. Approval is now being sought for an additional four years for $1 million funding per year from NIAID, with additional funds being contributed by partnering ICs and $750,000 per year from Brazil. It is estimated that there will be 8 to 10 awards made. Proposed NIAID research focus includes HIV/AIDS and its co-morbidities, anti-microbial resistance, arboviral infections, malaria, influenza, neglected tropical diseases, parasitic diseases, the role of immune responses in pathogenesis, and tuberculosis.

The current collaborative program with RSA (2015-2019) is jointly funded with the South African Medical Research Council (SAMRC) and NIH each contributing $20 million. Research focus is on tuberculosis, HIV/AIDS, and HIV/AIDS-associated malignancies. Accomplishments as of August 2018 include 58 publications, 69 graduate students and 13 postdocs supported, and 96 conference presentations. The renewal of this program is for five years, 2020–2024, with an estimated 20 to 25 awards. Funding will stay consistent with SAMRC contributing $4 million a year, NIAID contributing $1 million a year, and other NIH ICs contributing $3 million a year. NIAID research focus will be on HIV/AIDS and HIV/AIDS-associated malignancies, arboviruses and other emerging/re-emerging viral diseases, parasitic disease, sexually transmitted disease, tuberculosis, vector biology and control, and zoonotic diseases. Collaborations with historically disadvantaged institutions, underrepresented investigators from South Africa, investigators from Kenya, Lesotho, Uganda, and Zimbabwe, and early-career investigators are encouraged.

Reviewer comments for these initiatives were stated and addressed and then ARAC members were asked to cast their votes electronically.

Q: How do these initiatives compare with the current CIPRA grant that CAPRISA received and the ICIDERs program? Is there overlap of the studies?
A: CAPRISA is an organization now in South Africa and has a series of successfully-competed investigator-initiated R01s. The ICIDERs are a different program that DMID supports that is focused on very specific diseases. And while there could be complementarity, there is no requirement for complementarity. They are separate programs. The big different is that these initiatives presented today are co-funded and co-managed. Regarding overlap, it comes down to an application by application basis. If somebody is already funded for a project, that would be weeded out at the application stage.

Q: How do you envision making the connection between the U.S. researchers and those individuals at the underrepresented institutions in South Africa? Is this a role that OGR is going to play to connect people?
A: We encourage the scientists at the underrepresented institutions to study the literature the same way that other scientists reach out to each other and to find individuals that work in their field. We offered to provide assistance of that kind of advice about how they might find those partners, and we strongly encouraged those previously disadvantaged institutions to work with the advantaged institutions in South Africa as a partner within South Africa, and then link to the U.S. side. We are hoping that there will be a long period for applications so that we can facilitate some of these contacts.

Q: On the U.S. side, is there any interest in trying to get new investigators to work internationally?
A: There is a real interest in new investigators. That is why we encourage them to look at publications and see who's working in the same area of science but not yet working in South Africa.

Ballot Voting Outcome (U.S.-South Africa)
11 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Ballot Voting Outcome (U.S.-Brazil)
11 Approval
0   Approval with modification(s)
0   Deferral for further information
0   Disapproval

Public Comments

No public comments

VII. Adjournment

The meeting of the Council adjourned at 3:45 p.m., on Monday, September 17, 2018.

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

 

-s-

Anthony S. Fauci, M.D.

Chair, National Advisory Allergy and Infectious Diseases Council

Director, National Institute of Allergy and Infectious Diseases

01/08/2019

Date

 
-s-

Matthew J. Fenton, Ph.D.

Executive Secretary

National Advisory Allergy and Infectious Diseases Council

Director, Division of Extramural Activities

National Institute of Allergy and Infectious Diseases

01/03/2019

Date

 

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

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