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NIH National Advisory Allergy and Infectious Diseases Council

Minutes of Meeting: June 2, 2014

The 177th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:30 a.m. on Monday, June 2, 2014, 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 4:35 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 p.m. for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.

Council Members Present:

  • Dr. Adaora Adimora
  • Dr. Mavis Agbandje-McKenna
  • Dr. Norman Baylor
  • Dr. Robert Belshe
  • Dr. Enriqueta Bond
  • Dr. Anita Chong
  • Ms. Dázon Diallo
  • Dr. Diane Griffin
  • Dr. Jonathan Karn
  • Dr. Norma Kenyon
  • Dr. Velma Scantlebury
  • Dr. Larry Schlesinger
  • Dr. Arlene Sharpe
  • Dr. Georgia Tomaras
  • Dr. Christopher Wilson
  • Dr. Jerome Zack

Ex Officio Members Present:

  • MG Joseph Caravalho
  • Dr. Victoria Davey
  • Dr. Anthony Fauci
  • Dr. Bruce Gellin
  • Dr. Rima Khabbaz

Ad Hoc Members Present:

  • Dr. Daved Fremont
  • Dr. Alessandro Sette

Council Members Absent:

  • Ms. Maria Acebal
  • Dr. Michael Holtzman

NIAID Senior Staff Present:

  • Dr. Hugh Auchincloss
  • Dr. Carl Dieffenbach
  • Dr. Matthew Fenton
  • Dr. Charles Hackett
  • Dr. Carole Heilman
  • Dr. Clifford Lane
  • Dr. John Mascola
  • Dr. John McGowan

Table of Contents

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 4,098 research and training applications with primary assignment to NIAID for a requested amount of $1,790,546,027 in first-year direct costs and recommended approval of 2,031 applications with $687,544,736 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. Daved Fremont, associate professor of pathology and immunology, and biochemistry and molecular biophysics, Washington University, and Dr. Alessandro Sette, center head, division head, and professor, Center for Infectious Diseases, Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology.

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

Consideration of Minutes of Previous Meeting

Council considered the minutes of the January 27, 2014, meeting and approved them as written.

Staff and Organizational Changes

On April 11, President Obama nominated Sylvia Mathews Burwell to be the new secretary of the Department of Health and Human Services.

In March, President Obama announced the appointment of Douglas Brooks as director of the White House Office of National AIDS Policy.

In March, Dr. John Ruffin retired as director of the National Institute on Minority Health and Health Disparities. Dr. Yvonne Maddox will serve as NIMHD’s acting director.

In April, Secretary of State John Kerry swore in Dr. Deborah Birx as ambassador at large and U.S. global AIDS coordinator to lead U.S. government international HIV/AIDS efforts.

Dr. Fauci announced that Dr. Maria Giovanni was appointed associate director for genomics and bioinformatics, NIAID. She will continue to lead genomics and bioinformatics activities in the Division of Microbiology and Infectious Diseases.

Dr. Jennifer Reed has been appointed director of the Clinical Research Operations Program, DAIT.

Abe Mittleman, associate director of management and operations, Vaccine Research Center (VRC), retired last September. Dr. Hillery Harvey was appointed to fill this position.

In May, Emily Linde was named deputy director of the Grants Management Program, Division of Extramural Activities, and Dr. Kate White was selected as permanent director of the Office of Initiative Development, Office of Strategic Planning, Initiative Development, and Analysis.

Tributes and Awards

Dr. Fauci paid tribute to Dr. Albert Kapikian, former chief of the Epidemiology Section, Laboratory of Infectious Diseases, who passed away in February. Dr. Kapikian was known internationally for his research on viruses that cause gastroenteritis. In the 1970s, he and his colleagues identified Norwalk virus and hepatitis A virus. Dr. Kapikian and his coworkers’ research led to the development, testing, and approval of the first rotavirus vaccine.

Dr. Carolina Barillas-Mury, chief of the Mosquito Immunity and Vector Competence Section, Laboratory of Malaria and Vector Research, has been elected as a member of the National Academy of Sciences.

Dr. Fauci acknowledged five NIAID scientists who have been elected as fellows of the American Academy of Microbiology: Drs. Jeffrey Cohen, Kim Green, Peter Kwong, Thomas Nutman, and Ted Pierson.

Dr. Daniel Douek, senior investigator and chief of VRC’s Human Immunology Section, has been elected to the American Association of Physicians.

Dr. Joshua Milner, chief of the Allergic Inflammation Unit, Laboratory of Allergic Diseases, was elected as a member of the American Society for Clinical Investigation.

Meetings and Events

In March, His Holiness the Dalai Lama gave the annual J. Edward Rall Cultural Lecture at NIH. Tenzin Gyatso, the 14th Dalai Lama and a Tibetan Buddhist, received the Nobel Peace Prize in 1989. His NIH lecture was entitled “The Role of Science in Human Flourishing.”

Dr. Salim Abdool Karim delivered the John LaMontagne Memorial Lecture. He spoke about “Envisioning ‘The End of AIDS’: Challenges and Prospects.”

Also in March, Dr. Fauci delivered the keynote address at the first Global Vaccine and Immunization Research Forum. NIAID cohosted the forum with the World Health Organization and the Bill and Melinda Gates Foundation.

Last fall, NIAID implemented a process to examine the future direction of the Institute’s intramural research program. Dr. Fauci appointed a 14-member committee to conduct the review. Dr. Hugh Auchincloss served as an ex officio member. The committee’s charge was to determine the areas of scientific focus for the Division of Intramural Research (DIR) over the next 5 to 10 years, taking into account current scientific opportunities, budget constraints, and the unique capabilities of DIR. Dr. Fauci also asked the committee to consider the intermediate and long-range vision for DIR.

The overall goal for DIR is to maintain the highest possible scientific standards within the context of its unique characteristics. The committee issued its final report in May with recommendations aimed at better positioning the program for the future.

Budget Update

The President signed the FY 2014 budget into law on January 17, 2014. NIAID received an increase of 3.8 percent and NIH received an overall increase of 3.4 percent.

Dr. Fauci summarized NIAID’s financial management plan for FY 2014. NIAID will support a payline to the 9 percentile for established investigators and the 13 percentile for new and early-stage investigators. NIAID will not make programmatic adjustments to competing, unsolicited awards; noncompeting grants; or research and development. NIAID program initiatives will remain at levels that previously were cut by up to 20 percent in order to sustain investigator-initiated awards. NIAID’s estimated success rate will be between 20 and 22 percent.

On March 4, 2014, the President released his FY 2015 budget request to Congress, which includes an increase for NIH of 0.7 percent over the FY 2014 level.

Legislative Update

On February 3, Senate Assistant Majority Leader Dick Durbin visited NIH. He met with Dr. Collins, Dr. Fauci, and other institute directors to discuss promising NIH research developments. Also on February 3, Representative Joe Pitts, chair of the House Energy and Commerce Subcommittee on Health, toured NIH and met with Dr. Collins, Dr. Fauci, and other institute directors to discuss the importance of continued investment in NIH research.

On February 24, Senator Barbara Mikulski, chair of the Senate Full Appropriations Committee, visited the NIH Clinical Center to discuss the Omnibus Appropriations Act and what it means for NIH and its employees.

On March 26, Dr. Collins testified before the House Labor-HHS Appropriations Subcommittee on the future of biomedical research.

On April 2, Dr. Collins testified before the Senate Labor-HHS Appropriations Subcommittee on the FY 2015 NIH budget request.

On April 30, Dr. Fauci participated in a congressional briefing sponsored by amFAR on “Making AIDS History: From Science to Solutions.”

On May 7, Dr. Fauci briefed the Coalition for Life Sciences Congressional Biomedical Research Caucus on “HIV/AIDS in 2014: Progress and Priorities.”

Dr. Fauci recognized Dr. Michael Kurilla, director of the NIAID Office of Biodefense Research Activities, who testified before the House Labor-HHS Appropriations Subcommittee to address the HHS public health emergency medical countermeasures enterprise.

Other Information Items

Dr. Fauci gave brief updates on several HIV/AIDS studies. IMPAACT Study P1115 is assessing a large number of babies born to high-risk mothers. The babies will have antiretroviral therapy (ART) started within 48 hours of birth and be followed for a prolonged period to determine what percentage of them will actually be “cured.”

Another study, called the PARTNER study, is looking at the importance of treatment as prevention. In the first two years, there were no linked HIV transmissions with an HIV positive partner on ART if the ART brought the virus to undetectable levels.

Antimicrobial resistance continues to get attention, including from CDC, WHO, and the White House. In February 2014, the Institute posted NIAID's Antibacterial Resistance Program: Current Status and Future Directions 2014. FDA, NIH, CDC, and industry will hold a workshop in July 2014 on the development of new antimicrobial products.

Dr. Fauci noted some significant research on chikungunya done by our grantees and intramural program. He also gave brief updates on Middle East Respiratory Syndrome (MERS)-coronavirus and Ebola.

III. Guest Speaker—John R. Mascola, M.D., Director, Vaccine Research Center

Dr. John Mascola gave an overview of the leadership structure for the Vaccine Research Center (VRC). In October 2013, Dr. Fauci appointed him as permanent director of the VRC. Dr. Mascola asked two laboratory chiefs and senior investigators, Drs. Barney Graham and Richard Koup, to serve as co-deputy directors. Dr. Hillery Harvey is the new associate director of management and operations.

Over the last several years, VRC has built up three major translational research programs, a clinical trials program, an animal models translational research program, and a vaccine production program.

Dr. Mascola gave brief updates on some of the scientific research areas at VRC, including influenza, chikungunya and alphavirus, Ebola and Marburg viruses, respiratory syncytial virus, malaria, tuberculosis, and MERS.

He gave a detailed summary of the HIV antibody program and highlighted some recently published research. He presented some of the research being done that is looking at how antibodies can be used for prevention and treatment.

IV. Report of the Division of Allergy, Immunology, and Transplantation Council Subcommittee—Charles Hackett, Ph.D., Deputy Director, DAIT

Dr. Charles Hackett welcomed all of our Subcommittee members of the National Advisory Allergy and Infectious Diseases Council.

Dr. Hackett took the opportunity to inform the Subcommittee members that it was a pleasure to have Dr. Daved Fremont, Washington University in St. Louis present on “Correlating B Cell Epitopes With Protection. Also Dr. Alessandro Sette, La Jolla Institute for Allergy and Immunology, would be presenting “Immune Epitope Discovery: Insights Into Natural Immunity, Disease, and Vaccination.” In addition, Dr. Hackett noted that Dr. Stacy Ferguson, Basic Immunology Branch, would first give a general overview of “DAIT’s Immune Epitope Program.” She would follow this with a more specific discussion of the Division’s B Cell Epitope Discovery Program.” Additionally, Dr. Timothy Gondre′-Lewis, Basic Immunology Branch, would present the T Cell Epitope Discovery Program.”

Following the presentations, Dr. Hackett announced there were three research concept clearances for review and approval by the Subcommittee.

Fiscal Year 2015 Research Concept Clearance

Radiological and Nuclear Medical Countermeasure Product Development Program: The goal of this initiative is to provide funds to continue and expand nonclinical efforts for product development of radiological/nuclear medical countermeasures effective for the mitigation or treatment of acute radiation syndromes, radionuclide decorporation agents to treat internal contamination, and radiation biodosimetry products for inclusion in the Strategic National Stockpile for potential use during a radiological emergency.

The subcommittee endorsed and unanimously approved this initiative.

Immune Defense Mechanisms at the Mucosa Cooperative Studies Group: The objective of this initiative is to support innovative basic research projects on immune defense mechanisms and immune regulation at respiratory, gastrointestinal, and urogenital tract mucosal surfaces. The long-term goal is to develop the knowledge base needed to promote development of vaccines and therapeutics for protection from mucosal pathogens and mucosa inflammation.

The subcommittee endorsed and unanimously approved this initiative.

Asthma and Allergic Diseases Cooperative Research Centers:The initiative will support NIAID's unique and long-standing Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) program. This Program funds research centers across the U.S. to conduct interdisciplinary and translational research in asthma and allergic diseases. The Centers coordinate their efforts through a steering committee and collaborate with each other through an opportunity fund that supports small, independent pilot studies. A change in duration of awards from five years to seven years will be proposed. Longer grant duration allows the program to accommodate clinical trials of immune modulation and longitudinal cohort studies that are required towards the goal of asthma and allergic disease prevention.

The subcommittee endorsed and unanimously approved this initiative.

V. Report of the Division of Microbiology and Infectious Diseases—Carole Heilman, Ph.D., Director, DMID

Dr. Carole Heilman, director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on June 2, 2014. After welcoming the Subcommittee, Dr. Heilman introduced new ex officio member Colonel Michael Kozar, chair of the U.S. Army Medical Research and Materiel Command (USAMRMC). She also acknowledged Dr. Joe Larsen, a branch chief at the Biomedical Advanced Research and Development Authority within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, who participated in today’s meeting on behalf of Dr. Robin Robinson, director of BARDA. She then referred to the branch chiefs and office directors to introduce new staff in their respective programs.

Following introductions and general programmatic updates, Dr. Heilman shared two proposed DMID topics for inclusion in the upcoming NIH-wide SBIR contract solicitation for the Subcommittee’s consideration:
  1. Methods of Clinical Sample Preparation for Rapid Detection of Bacterial Pathogens, which would support the development of rapid, highly sensitive, easy-to-use, cost-effective clinical diagnostics that can identify gram-negative hospital-associated bacterial pathogens and determine antibiotic susceptibilities.
  2. Development of Novel Influenza Antivirals, which would support preclinical development of a novel small molecule therapeutic intervention with broad antiviral activity against multiple influenza A subtypes, including drug-resistant strains.

Dr. Heilman then introduced Dr. Dennis M. Dixon, chief of DMID’s Bacteriology and Mycology Branch, who reported on DMID’s current antimicrobial resistance research efforts.

Update: DMID’s Antimicrobial Resistance Research Activities

Dr. Dixon provided an overview of DMID’s antimicrobial research program, which includes a robust array of activities spanning basic, translational, and clinical research, all designed to address the growing public health problem of antimicrobial resistance. He noted a recent NIAID publication, NIAID’s Antibacterial Resistance Research Program: Current Status and Future Directions, which summarizes ongoing activities in each of these areas, basic translational and clinical research. Dr. Dixon described several specific efforts currently underway, including targeted trials designed to identify ways to reduce the risk of antimicrobial resistance by reducing and/or optimizing the use of licensed antibacterials and the recently established Antibacterial Resistance Leadership Group. Finally, he described several innovative approaches based on the latest scientific advances that NIAID is currently pursuing to mitigate the emergence of resistance.

Concepts Presented for Clearance

Development of Therapeutic Products for Biodefense and Emerging Infectious Diseases: This proposed initiative is designed to advance the translation of promising therapeutic products against biothreat pathogens and emerging infectious diseases from lead candidate to first-in-human clinical trials. The concept was enthusiastically received by the DMID Subcommittee who applauded the evolution of the portfolio, which began focused on a small subset of pathogens but now includes products that address emerging diseases, in addition to filling gaps in the biodefense arena. The DoD representative in attendance supported the initiative and noted that the current pipeline of products supported by DMID under similar initiatives includes several strong performers. A comment was made acknowledging the relationship between the R01 partnership and the broad agency announcement (BAA), which is the mechanism that will be used to support this activity. Program staff described how the partnership serves as a pathway to prepare a product for BAA support; the partnership supports early to mid-stage translational research, while the BAA supports advanced product development, culminating in possible phase I clinical trial support. The concept was unanimously approved by the Subcommittee.

Systems Biology and Antibacterial Resistance: This proposed initiative will support multi-disciplinary systems biology research that employs high-throughput ‘omics technologies, sophisticated data analysis pipelines, and computational modeling techniques to identify and investigate genome-wide molecular interaction networks of the pathogen and the host in response to treatment of antibacterial resistant infections. The focus will be on high-priority bacterial pathogens with established resistance. Subcommittee members commented that the proposed initiative is important and timely, and will make available new tools and approaches to understand the emergence of antibacterial resistant pathogens, which could facilitate the development of new drugs to address infections caused by these pathogens. A suggestion was made to encourage the use of the proposed approach in clinical research to validate the systems biology studies typically done using animal models of infectious diseases. The concept was unanimously approved by the Subcommittee.

Partnerships - the following two Partnerships concepts were presented:
  • Non-Traditional Therapeutics That Limit Antibacterial Resistance - to support the discovery and development of non-traditional approaches to combating infectious disease with the goal of circumventing the trend towards increasing antibiotic resistance.
  • Partnerships for Host-Targeted Therapeutics to Limit Antimicrobial Resistance - to provide support for preclinical development of selected candidate therapeutics that target host-encoded functions required for infection, replication, virulence, proliferation, and/or pathogenesis of infectious diseases.

The Subcommittee strongly supports the DMID Partnerships Program, noting that it complements related DMID research and product development-related objectives and provides an important mechanism to assist the academic and industrial communities in translational research and development efforts. Additionally, the Program is viewed as critical in stimulating innovative translational efforts, vetting of candidate products, and leveraging resources within the industrial community. There is appreciation for the dual mechanism approach to support early-stage and later-stage Partnerships activities: the R21/R33 mechanism for high-risk early-stage translational activities, and the milestone-driven R01 mechanism for later-stage preclinical and product development activities. The Subcommittee favored the requirement for substantive investment by an industrial partner in R01 Partnerships projects.

Several Subcommittee members noted that the ongoing external evaluation of the Partnerships program is appropriate, particularly in regard to our dual mechanism approach. Program clarified that the external evaluation will focus only on prior U01 and R01 awards that have been completed before 2010; evaluation of the R21/R33 mechanism, which was initiated for Partnerships in FY2012, will occur in the future.

One Subcommittee member asked about coordination of the Partnerships program with SBIR/STTR programs. Program staff explained that although the two programs are somewhat independent, eligible applicants were strongly encouraged to take advantage of the SBIR/STTR program for parallel and/or follow-on support. The Subcommittee member asked how resources and objectives are partitioned between the Partnerships and SBIR/STTR programs. Program staff explained that the two programs differ significantly in terms of applicant eligibility, scope, and budgetary source. The Partnerships program was described as complementary to the SBIR/STTR program and open to a broader community including foreign researchers/institutions ineligible for SBIR/STTR support.

The Subcommittee strongly supported the prioritized research foci of the individual Partnerships concepts and viewed both as key components of the antimicrobial resistance research and development portfolio. One Subcommittee member pointed out that the targeted community for the R01 initiative may have to be carefully defined to achieve balance between viral and bacterial pathogen priorities. Program agreed and explained that the final priority criteria will be developed as the RFA is drafted. Another Subcommittee member asked if a candidate antibacterial that also exhibited a host-targeted effect would be responsive to the R01 initiative. Program staff replied that such a candidate would be responsive if supported by sufficient proof-of-principle. The two concepts were unanimously approved.

Report: The NIAID Extramural Funding Portfolio-Finding the Right Balance

Dr. Matthew Fenton, director of NIAID’s Division of Extramural Activities, provided the Subcommittee with a special report concerning NIAID budgetary and training issues. Dr. Fenton spoke about NIAID’s unique mission to address a broad array of high profile scientific issues while maintaining readiness to respond quickly to emerging and reemerging disease threats as they arise. He noted that this mandate is particularly challenging in times of fiscal restraint. Dr. Fenton reported that our budget allocation is further divided into solicited and investigator-initiated budget allocations, which are determined by Institute leadership, with input from the research community. It was noted that compared to the Institute as a whole, a far lower percentage of DMID grant dollars go into the solicited portfolio. According to Dr. Fenton, on average, 25 percent of the Institute's budget turns over every year as solicited programs expire and need to be renewed or new programs develop. Dr. Fenton also described some of the factors and considerations that go into determining the balance between solicited and investigator-initiated allocations. Finally, Dr. Fenton reported on recent trends for training awards, including career development and fellowship grants; noted actions taken in recent years to enhance training opportunities; and discussed NIH and NIAID perspectives under consideration to support the biomedical workforce of the future.

VI. Joint Meeting of the AIDS Subcommittee, National Advisory Allergy, and Infectious Diseases Council and AIDS Research Advisory Committee (ARAC)—Carl Dieffenbach, Ph.D., Director, DAIDS

The AIDS Research Advisory Committee met on Monday, June 2, 2014, from 1:00 p.m. to 5:00 p.m., at the Natcher Conference Center on the NIH campus in Bethesda.

Participating members included: Jerome A. Zack (Chair), Adaora Adimora, Dázon Diallo, Earnest Hopkins, Jonathan Karn, Stephen Mason, Francine McCutchan, David O’Connor, Deborah Persaud, William Powderly, Georgia Tomaras, and Chris Wilson; ex officio member, Vicky Davey, and Office of AIDS Research Advisory Council Committee (OARAC) Liaison, Myron Cohen, also participated. NIAID representatives included Carl Dieffenbach, Emily Erbelding, Diana Finzi, Mary Marovich, Sarah Read, and Sheryl Zwerski. Mark Mueller served as executive secretary.

Welcome and Approval of Minutes
Jerome Zack, Ph.D., Chair, ARAC

Dr. Zack welcomed the ARAC members, DAIDS representatives, and guests. ARAC members approved the minutes of the January 27, 2014, ARAC meeting without change.

Director’s Report
Carl Dieffenbach, Ph.D., Director, DAIDS

Dr. Dieffenbach welcomed the attendees and acknowledged the confirmation of Dr. Deborah Birx, a former ex officio member of ARAC, as the new ambassador at large and U.S. global AIDS coordinator to lead all U.S. government international HIV/AIDS efforts. Dr. Birx will also continue to participate in the NIH, DAIDS Strategic Working Group.

Budget

Dr. Dieffenbach reviewed the budget tables presented to the Council; the President’s 2015 budget allows a small increase for NIAID that largely represents the $15 million, which will come to the NIAID for the NIH-HIV Cure Initiative, as per an agreement with the NIH Office of AIDS Research (OAR). Essentially, NIAID funding remains level.

Public Health Service (PHS) 2015-1 Solicitation for NIH and Centers for Disease Control and Prevention (CDC) Small Business Innovative Research (SBIR) Contract Proposals-DAIDS Topics

In compliance with a Congressional requirement for an SBIR set-aside, DAIDS has been exploring additional ways to foster productivity in the use of SBIR contracts. Dr. Dieffenbach presented two concepts for potential products that could be developed using SBIR contracts. The contracts complement the grant mechanism, and the projects are expected to be phase I through phase III awards depending on the milestones.

The two SBIR concepts were the following:

  • Inhaled Delivery of Clofazimine (CFZ)-An Important Antituberculosis Drug. The objective is to develop an inexpensive, easy-to-use, inhaled delivery system for CFZ to be used with combinations of systemic antitubercular drugs. Members had no questions after an explanation of the phase I activities and envisioned phase II activities.
  • Small Inexpensive Unit for Removing Cells From Small Amounts of Blood in Resource Limited Settings. The objective is to develop an easy-to-use, inexpensive method for removing cells from very small amounts of blood for use with point-of-care (POC) HIV viral load assays. A Committee member asked whether prior discussion [on the proposed unit] occurred about saving the peripheral blood mononuclear cells (PBMCs) after removal of plasma. Cell-associated viral load might be important for staging. Dr. Dieffenbach suggested it may be possible to save the cell pellet to isolate cell-associated DNA that could be used in many potential applications, including direct comparison in sequence-based characterization of reservoirs. Additional discussion points included:
    • The cell removing unit is envisioned as a cartridge for POC sample preparation in which material would be pushed through, generating different layers—red blood cells first, then elution from the plasma of other components or analytes.
    • The unit would expand POC for viral RNA to include a reasonable add-on of cell-associated DNA.
    • The unit technology would be complementary to dried spot technology, not necessarily replacing it.
    • The effect on the low end of viral load testing in the context of POC viral loads was questioned. It was noted that an appropriate dynamic range needs to be set to include the low end of viral load, within the confines of a quality assessment (QA) program.

Members were asked to mark their ballots, and ballots were collected.

Director Request–Suggestion for Discussion at his ARAC Midpoint Member Teleconferences

  • Dr. Dieffenbach suggested using future midpoint calls to solicit Committee member ideas for the SBIR contract. The SBIR money that is taken out of the NIH budget each year is growing per act of Congress, and it would be beneficial to generate more feedback and research ideas.
  • Another topic for midpoint call discussion will be the size and scope of the Martin Delaney Collaboratories.

Programmatic Updates

The NIH HIV Cure Initiative is a project to which the U.S. will redirect $100 million for the generation of new HIV therapies with the goal of long-term remission or complete elimination of the virus, without requiring lifelong therapies. To date, approximately 56 percent of the $100 million has been programmed into FY 2015 and FY 2016 with the expectation, through planning processes and discussions with the OAR and the other institutes, to program out the rest of the funds, either FY 2016 or FY 2017 and beyond.

On February 5, 2014, a request for information (RFI) was published, requesting information from the scientific community regarding the high-priority research areas of HIV persistence and strategies to eradicate and control HIV. Publication of the request was coordinated with the scheduled annual Conference on Retroviruses and Opportunistic Infections (CROI) and Keystone HIV meeting, both held in March, to allow greater scientific discussion and response.

On May 28, 2014, a webinar was held that reported the results of the RFI. The webinar, sponsored by OAR and NIAID, had over 700 registrants and nearly 400 active participants. The overarching comments from the RFI emphasized: 1) improving the mechanistic understanding of HIV latency and persistence along with developing better assays and biomarkers; 2) maintaining and expanding state-of-the-art assays with online access to procedures; 3) providing curated reagent samples and methods; and 4) furnishing a platform for focused clinical evaluation of cure strategies and a clearinghouse for information with distribution of positive and negative results.

The first set of the solicitations will be published in June, aiming for the first round of funding in late 2014, hopefully November-December, to meet a goal of having NIH HIV Cure Initiative grants funded within one calendar year of the release of the request. Starting in FY 2015, NIH will solicit R01s and R21s concerning basic research on mechanisms of persistence and latency. The solicitation will be inclusive, reflecting the interests of all the institutes and will be reviewed by the Center for Scientific Review. Using standard receipt and referral, the central request for applications will allow central review and percentile ranking, so the institutes can cooperatively determine the highest priority applications and the most meritorious for funding.

Additionally, immunological strategies will be solicited using a contract-based strategy to fully engage the pharmaceutical industry in the development of therapeutic vaccines as well as other immunological strategies. NIAID would like greater pharmaceutical involvement within individual collaboratories and a mechanism to permit a single collaboratory to participate in ventures with more than one pharmaceutical partner. The current thinking is for more focused collaboratories on a single topic or target—smaller collaboratories, greater in number, with resources to collaborate with each other as needed.

During the discussion, it was noted that by definition, collaboratory grants are usually for five years with a requirement to renew or recompete at the end of the five-year period. After five years, the progress of the existing three collaboratories will be evaluated, including what worked or did not work, any systemic problems, and needed improvements. If the collaboratory scope is downsized, the existing collaboratories would have to evolve, analogous to outgrowths or product divisions within a company.

Future Meetings:

  • June 3 to 4, 2014 – AIDS Vaccine Research Subcommittee (AVRS) Meeting
  • September 15, 2014 – ARAC
  • September 16 to 17, 2014 – SWG
  • January 26, 2015 – ARAC
  • January 27 to 28, 2015 – SWG or AVRS
  • TBD – Prevention Networks Joint Meeting

Office of AIDS Research Advisory Council (OARAC): Update
Myron S. Cohen, M.D., OARAC Liaison

In November 2013, the OARAC was asked by Dr. Francis Collins, director, NIH, to submit a white paper, detailing the vision across all the institutes concerning the future of investments towards AIDS research. Specifically, the Committee was charged to: 1) determine the key unanswered scientific questions in areas of interest; 2) determine the highest research priorities in the particular areas in the next three to five years; and 3) determine whether the concerns unique to specific at-risk populations are being adequately addressed. A working group was delegated this task, and sources of input included presentations at an April 10th meeting, along with the Trans-NIH Plan for HIV-Related Research, and comments from many different organizations. A draft document was circulated to the members of the OARAC on May 20th, which received the endorsement of the overall committee subsequent to comments. The report, which has been submitted to Dr. Collins, will be presented formally to the Advisory Committee to the Director on June 6th. If the report becomes available, it will be sent to ARAC members.

Concept Review (approval requested)

Nine FY 2016 research initiatives were presented for approval, including two from the Prevention Sciences Program (PSP); one from the PSP and Therapeutics Research Program (TRP); two from the Basic Sciences Program (BSP); two from the Vaccine Research Program (VRP); and two solely from TRP.

The BSP concepts concern targeting persistent HIV reservoirs (TaPHIR) and a U.S.-China program for research towards a cure are supported by exploratory and development grants (R21/R33) and the R01 mechanisms, respectively. The VRP concepts addressing staged vaccine development (SVD) and HIV vaccine research and design (HIVRAD) are supported respectively by a research and development contract (N01) and a research program projects mechanism (P01).

Discussion Points:

  • Prevention Sciences Program (PSP) concepts
    • Integrated Preclinical/Clinical Program for HIV Microbicides and Biomedical Prevention (IPCP-MBP) (U19 Cooperative Agreement). The objective is to stimulate a strong, diverse base in preclinical discovery and development of nonvaccine biomedical prevention (nBP) products; develop single and combination noncoital and sustained prevention vaginal, penile, and/or rectal products/strategies; and support transition of nBP products to clinical testing. The concept puts increased emphasis on underserved populations, including post-menopausal women, Black or Hispanic gay men, men who have sex with men (MSM), transgenders, and those experiencing sexual violence and trauma. The renewed concept encompasses all nBP approaches to prevention targeting noncoital (7 day protection from HIV infection), and sustained release (>30 days protection, and focuses IPCP-MBP support on sustaining the nBP prevention pipeline.
    • Increased Knowledge and Innovative Strategies to Reduce HIV Incidence-iKnow (R01). This concept’s objective is to support the development of new research methods and strategies to identify, engage, and successfully treat people who are unaware of their HIV infection. It specifically targets populations at high risk of HIV infection and who have a high proportion of undiagnosed cases, including, for example, young African American MSM in the U.S., adolescent women in South Africa, African American women at high risk for HIV infection, and people who inject drugs. One reviewer was happy that African American women at high risk were included. The concept addresses very diverse groups, probably requiring very different approaches. A suggestion was made to expand the population coverage (populations of interest) in the announcement with special receipt, referral, and/or review considerations (PAR) to encourage appropriate applications. Groups to be addressed depend on applications received.
  • Joint PSP and Therapeutics Research Program (TRP) concept
    • Adherence to ARV-Based Treatment and Prevention (R01). The objective is to support the development of bioanalytical tools to measure adherence to ARVs for treatment and prevention of HIV. It elicited a question from reviewers about the feasibility of the initiative—parallel and needed objectives that cannot be accomplished concurrently. Specifically, the problem is using available, possibly inadequate, assays to do implementation research. The response was the investigators do not necessarily need to include work on both of the RFA objectives. For example, if one proposed assay is very early in development, a feasibility study would not be in order.
  • Basic Sciences Program (BSP) concepts
    • Targeting Persistent HIV Reservoirs (TaPHIR) (R21/R33). Purpose is to develop innovative approaches for studying and specifically targeting persistent HIV reservoirs. This is a renewal. The first awards under the previous program will not reach the transition stage to the R33 phase until early next year. Typically, for similar programs, a cross-disciplinary group of program officers reviews the milestones after completion of the R21 phase and then a consensus decision is made on what deserves continued funding, with only about half the R21s proceeding to the R33 phase. If the research does not make the cut, the investigators are eligible for and encouraged to apply for an R01. R21s may request no-cost extension if more time is needed. The internal reviewers are keenly aware of gaps in the current grant portfolio and try to fund applications that complement existing grants. Under this program, new investigators are handled the same way as well-established investigators. If they do transition successfully from the R21 to the R33 phase, one caveat is loss of eligibility as a new investigator since R33 is considered as an R01 level of funding. Options for submitting applications with established principal investigators are explained to candidates.
    • U.S.-China Program for Research Toward a Cure for HIV/AIDS (R01). OAR is sponsoring with NIAID taking the lead. U.S.-China’s objective is to stimulate collaborative research opportunities between investigators in the U.S. and China focused on research toward a cure for HIV/AIDS. It is valuable for several reasons—for an ongoing dialogue and to stimulate research and leverage resources on both sides with the potential for synergy between groups in the U.S. and China. The reviewers expressed concerns about ethical considerations and appropriate studies for all human subjects, especially regarding pediatric cure research and treatment interruptions with children. The reviewers advised extra vigilance regarding these concerns. The wording of the funding opportunity announcement is being looked at closely to emphasize interest in studies investigating early treatment in individuals of all ages. Treatment interruption is not a large component. There will be two separate applications; one for U.S. and one for China. A precedent has been established for a model review committee in the U.S. and China to reach a consensus on funding decisions in the two countries. That committee is the 2012 trans-NIH program of biomedical research for U.S.-China collaborations.
  • Vaccine Research Program (VRP) concepts
    • Staged Vaccine Development (SVD) (N01, BAA). The objective is to position NIAID/VRP to commence rapidly with the manufacture of promising candidate vaccines that have shown safety and immunogenicity in preclinical/early clinical trials for use in advanced clinical trials. Approval for advancing a vaccine concept through this mechanism involves review through an internal-external review group called the Vaccine Research and Development Resources Group (VDRG) to assess scientific merit of the proposed product concept. The financial risk shared by industry is company-dependent—each company has a different cost-sharing formula. The real gain in this program may be in the infrastructure provided by industry and in advancing intellectual property or trade secrets that help move a platform forward. Recommended to be aware of how success will be measured and possibility of sunk cost investment if process development has low success rate. Phase I will be mainly safety.  Go/No Go criteria for advancing into manufacturing will be from clinical data with specific criteria incorporated into clinical trial design.
    • HIV Vaccine Research and Design (HIVRAD) (P01). This renewal will support multi-disciplinary projects that address important scientific questions relevant to AIDS prophylactic vaccine discovery research. After presentation of past accomplishments and supported research areas, reviewers had no questions. Reviewers had comments that continuing this mechanism is essential and liked the language on translational activity.
  • Therapeutics Research Program (TRP) concepts
    • Mechanisms of Immune Protection from TB among HIV-Infected Individuals (R01). This concept’s objective is to characterize genetic, epigenetic, and immunological correlates of Mtb infection protection in highly-exposed individuals in the context of HIV infection. It elicited a suggestion to expand the definition of immune protection and how individuals who are immune protected would be identified. The response was, in terms of skin testing, previous investigators have clarified, to some extent, the definition of immune protection. For example, one phenotype was referred to as history of close-contact (usually household) exposure and persistently TB skin test negative based on a minimum of two years of observation. The main problem is the lack of a gold standard to prove absence of infection, i.e., possible false-negative reaction to the tuberculosis skin test (TST or PPD skin test) or the interferon gamma release assay (IGRA). Another issue to be addressed is dependence on presumptive assessment scales for probability of true exposure. To summarize, the challenge to be met involves imperfect tests to assure lack of infection and imperfect ways to ascertain intensity and duration of exposure. These factors must be taken into account in calculation of sample size—the more uncertainty in the tests, the larger the sample size needs to be in order to compensate.
    • Limited Competition: Strategic Timing of Antiretroviral Treatment (START) (UM1 Cooperative Agreement) will support the continuation and conclusion of the START trial, providing data from a randomized, controlled trial to address the question of when to start antiretroviral treatment in patients with CD4>500. Reviewers agree more definitive data are needed to scientifically underpin the risk/cost-benefit of cART in the higher CD4 strata. If the study runs until December 2016 to reach endpoints, there will only remain five months of funding to complete analysis. Contingencies to deal with such an outcome should be considered. Program expects sufficient funds for analyses will be available. If needed, an extension will be considered.

The ARAC members expressed support for each of the concepts and marked their ballots.

VII. Adjournment

The meeting of the Council adjourned at 4:05 p.m., on Monday, June 2, 2014.

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

7/28/2014
Date
-s-

Matthew Fenton, Ph.D.

Executive Secretary

National Advisory Allergy and Infectious Diseases Council

Director, Division of Extramural Activities

National Institute of Allergy and Infectious Diseases

7/23/2014
Date

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

Last Updated August 13, 2014

Last Reviewed August 13, 2014