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NIH National Advisory Allergy and Infectious Diseases Council

Minutes of Meeting: February 1, 2010

The 164th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:30 a.m. on Monday, February 1, 2010, 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 11:40 a.m. and from 1:00 p.m. to 4:30 p.m. The meeting was closed to the public from 8:30 a.m. to 10:00 a.m. and from 11:40 a.m. to 1:00 p.m. for review and consideration of individual grant applications and a survey by the Office of Extramural Research. Notice of the meeting was published in the Federal Register.

Council Members Present:

  • Dr. Robert Brooks
  • Dr. Carol Carter
  • Dr. Connie Celum
  • Dr. Satya Dandekar
  • Mr. William McLin
  • Dr. Louis Picker
  • Dr. Regina Rabinovich
  • Dr. Marc Rothenberg
  • Dr. George Siber
  • Dr. Samuel Stanley
  • Dr. Jenny Ting
  • Dr. Christel Uittenbogaart
  • Dr. Christopher Walker
  • Dr. Richard Whitley
  • Dr. David Wilkes

Ex Officio Members Present:

  • Dr. Anthony Fauci
  • Dr. Bruce Gellin
  • MG James Gilman
  • COL Kent Kester
  • Dr. Ronald Valdiserri

Council Members Absent:

  • Dr. Ann Arvin
  • Dr. Nelson Chao
  • Dr. Sharon Kiely

Ex Officio Members Absent:

  • Dr. Mitchell Cohen

Ad Hoc Members Present:

  • Dr. William Kwok

NIAID Senior Staff Present:

  • Dr. Hugh Auchincloss
  • Dr. Carl Dieffenbach
  • Dr. Carole Heilman
  • Dr. Marvin Kalt
  • Dr. Cliff Lane
  • Dr. John McGowan
  • Dr. Daniel Rotrosen

Table of Contents

I. Review of Grant Applications

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

Funding Actions: The Council reviewed 2,557 research and training applications with primary assignment to NIAID for a requested amount of $825,948,255 in first-year direct costs and recommended approval of 82 applications for $174,946,161 in first-year direct costs. Six Method to Extend Research in Time (MERIT) awards were recommended for approval.

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

Dr. Fauci opened the Council session by welcoming visitors to the meeting. He announced the appointment of four new Council members: Dr. Connie Celum, University of Washington; Dr. George Siber, Genocea Biosciences, Inc.; Dr. Jenny Ting, University of North Carolina at Chapel Hill; and Dr. Nelson Chao, Duke University. Three Council members, Drs. Arvin, Chao, and Kiely, were unable to attend the meeting. Also, ex officio member, Dr. Mitchell Cohen was unable to attend the meeting. Since Dr. Cohen will retire as director of the Coordinating Center for Infectious Diseases, National Center for Infectious Diseases, CDC, on May 1, Dr. Fauci thanked him for this service to the Council.

Dr. Fauci introduced ad hoc Council member, Dr. William Kwok, Benaroya Research Institute.

Consideration of Minutes of Previous Meeting

Council considered the minutes of the September 14, 2009, meeting and approved them as written.

Consideration of Operating Procedures

Council reviewed the 2010 Council operating procedures and adopted them as written.

Appointments by the Obama Administration

In January, Dr. Regina Benjamin was sworn in as the 18th Surgeon General of the United States Public Health Service.

Staff and Organizational Changes

Dr. Fauci announced several new appointments in the Institute. Dr. Patrick Duffy was named chief of the Laboratory of Malaria Immunology and Vaccinology in the Division of Intramural Research. In the Division of AIDS, Dr. Scott Proestel is the new deputy director of the Office of Policy in Clinical Research Operations.

Tributes and Awards

Dr. Michael Lenardo, a senior investigator in the Laboratory of Immunology, Division of Intramural Research, was named a fellow of the American Association of the Advancement of Science for his discovery of important regulatory pathways in human genetic diseases of immunoregulation and for founding several innovative international collaborative programs to advance biomedical research and training.

Dr. Fauci announced that in October, Dr. Ruth Kirschstein died. Dr. Kirschstein was the first female director of an NIH institute, the National Institute of General Medical Sciences, and served as NIH deputy director, acting NIH director, and senior advisor to multiple NIH directors.

In November, we mourned the loss of Dr. Josiah Wedgwood, who was chief of the Immunodeficiency and Immunopathology Section, Clinic Immunology Branch, Division of Allergy, Immunology, and Transplantation.

Budget Update

Dr. Fauci gave an update on the FY 2010 budget. The overall NIH allocation for 2010 is $31 billion, a 2.3 percent increase over FY 2009. NIAID received $4.8 billion, an increase of 2.6 percent over FY 2009.

He discussed several uncertainties and how they could impact the budget. First, it’s likely that NIAID could receive many R01 applications in late FY 2010 when PIs recycle their unsuccessful NIH Challenge Grant applications. Second, PIs will probably apply for new funding when the nearly 1,000 grants supported with American Recovery and Reinvestment Act (ARRA) funds expire. We expect these additional applications to strain the payline.

Because of these uncertainties, NIAID is taking a conservative approach to protect the budget early in the year by setting an interim R01 payline at the 8 percentile. NIAID does not expect to set final paylines until the spring.

Dr. Fauci revisited the purpose of ARRA and outlined how NIAID is using its ARRA funds. More than 70 percent of NIAID ARRA funds are supporting research project grants. Only a small percentage is supporting solicited initiatives and signature projects. In addition, NIH set aside $250 million for flu research, mostly for contracts testing H1N1 vaccines.

Legislative Update

On September 29, 2010, Dr. Fauci participated in a hearing entitled “The Administration’s Flu Vaccine Program: Health, Safety, and Distribution.” His testimony focused on NIH’s research response to the pandemic caused by the novel 2009 H1N1 influenza A virus.

On November 4, Dr. Fauci briefed members of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education and Related Agencies on the role of NIH-supported research in response to the 2009 influenza pandemic.

Since May 2009, Dr. Carole Heilman, director, Division of Microbiology and Infectious Diseases, and other DMID staff have participated in weekly briefing calls with Congressional staff to inform the House and Senate leadership and committee staff about the results of NIAID’s vaccine clinical trials.

Dr. Fauci thanked Dr. Gray Handley, NIAID associate director for international research affairs, for his assistance in organizing and participating in a House Appropriations Committee staff visit to NIAID and CDC program sites in Thailand.

Other Information Items

On September 30, 2009, President Obama visited NIH and used this forum to explain how some of the ARRA money is being used.

In the January 1, 2010 issue of Science, Dr. Francis Collins put forth five key issues of preference for his tenure as NIH director: high throughput technologies, translational medicine, benefitting health care reform, focusing more on global health, and reinvigorating and empowering the biomedical research community.

Dr. Fauci spoke about the importance of global health issues. NIH held a productive two-day NIH Global Health Research meeting in Bethesda on January 5 and 6. Also, President Obama called for a comprehensive global health strategy, and the White House plans to release a global health initiative document outlining the strategy and vision.

Dr. Fauci mentioned that in the top 10 medical breakthroughs for 2009, Time magazine identified two supported by NIAID: the HIV vaccine and H1N1 vaccine. Last year in Thailand, investigators had the first positive signal of efficacy in an HIV vaccine clinical trial. He discussed building on the findings from the trial and plans to move forward.

In other news, Dr. Fauci noted that NIAID is partnering with the District of Columbia and launched a D.C. Partnership for HIV/AIDS Progress. Also, he gave an update on the 2009 H1N1 influenza pandemic and efforts to get people vaccinated.

III. Guest Speaker—Toni Scarpa, M.D., Director, Center for Scientific Review

Dr. Toni Scarpa presented some of the changes that have taken place in the Center for Scientific Review (CSR) over the last several years.

CSR shortened the amount of time from receipt of application to review. The time was cut in half, from about six months to less than three months.

To help reviewers who cannot come to Washington for a two day meeting three times a year, CSR now has two types of electronic reviews that they can use. One is a virtual face-to-face review where cameras and software allow 25 people to connect by computer to discuss applications. The other is an internet-assisted review that is essentially an internet-based discussion.

CSR is also using a review method that is comparable to an editorial board review by a scientific journal. In this case, the study section plays the role of the review board, deciding and comparing scores and assessing impact and significance.

To recruit and retain the best reviewers, CSR moved one out of the three annual meetings to the West Coast.

To reward reviewers, CSR eliminated deadlines for study sections members, so they can submit their grant application anytime. CSR extended this benefit to Council members and frequent reviewers.

Dr. Scarpa outlined the changes from enhancing peer review. These changes include a new scoring system, shorter applications, more emphasis on impact and significance, and changes to summary statements and the order of review for applications.

IV. Report of the Division of Allergy, Immunology, and Transplantation Council Subcommittee—Daniel Rotrosen, M.D., Director

DAIT Staffing/Organizational Changes: Dr. Rotrosen welcomed the subcommittee members of the National Advisory Allergy and Infectious Diseases Council. Dr. Rotrosen took the opportunity to inform the subcommittee members there would be an update given by Dr. Michael Minnicozzi, Asthma, Allergy and Immunology branch on “The Overview of the T-Cell allergen Epitope Contracts.” He proceeded to let the members know also, that Dr. William Kwok, Ph.D, Member, Benaroya Research Institute would be presenting “Allergen Specific CD4+ T-cells-A HLA Class II Tetramers.

Following an overall thought-provoking scientific presentation, Dr. Rotrosen acknowledged there were 5 concepts for review and approval.

The following concepts were presented for the Subcommittee’s consideration:

Cooperative Study Group for Immune Defense Mechanisms at the Mucosa: This program will solicit basic, applied, and clinical research applications with the potential to increase understanding of immunity at mucosal surfaces. Research supported by this program will be expected to break new ground and address key questions in mucosal immunity and immune defense. The goal is to gain new insights that will facilitate future development of vaccines and immunotherapies to protect mucosal surfaces from infection and inflammation. The subcommittee unanimously approved this initiative.

Small Grants on Primary Immunodeficiency Diseases (R03)/Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21): This initiative will solicit small projects in primary immunodeficiency disease and encourage investigators to conduct research in this area. Of particular interest is that this initiative will provide encouragement to investigators who will become early-stage investigators and new investigators when these projects mature into R01 applications. Research areas solicited by this initiative will include:

  • Identifying the clinical, immunological, and molecular characteristics of genetically determined immunodeficiency diseases.
  • Identifying the molecular basis of primary immunodeficiency diseases.
  • Advancing our understanding of how a genetic variant results in immunodeficiency.
  • Discovering/developing improved diagnostic/newborn screening tools for primary immunodeficiency disease.
  • Discovering/developing new animal models for primary immunodeficiency disease.

The Subcommittee endorsed and unanimously approved this initiative.

NIAID Division of Allergy, Immunology, and Transplantation: Clinical Products Distribution Group: This initiative will provide clinical site monitoring for trials conducted by the Immune Tolerance Network (ITN) and investigator-initiated (U01) clinical trials, and provide additional auditing/monitoring, as needed, for DAIT-supported clinical trials monitored by other DAIT-supported contracts or grants. At U.S. and international clinical sites and pharmacies where DAIT-supported clinical trials are conducted, this initiative will:

  • Perform on-site monitoring of the conduct/compliance with Good Clinical Practices (GCP).
  • Monitor laboratory facilities and procedures for obtaining, testing, and storing clinical research specimens.
  • Train site personnel in GCP and in the policies and procedures established by DAIT/ITN, NIH, FDA, and the HHS Office for Human Research Protections.
  • Recruit and train site monitors.
  • Prepare reports on monitoring findings and training activities.

NIAID Division of Allergy, Immunology, and Transplantation: Clinical Site Monitoring Group: This initiative will provide clinical site monitoring for trials conducted by the Immune Tolerance Network (ITN) and investigator-initiated (U01) clinical trials, and provide additional auditing/monitoring, as needed, for DAIT-supported clinical trials monitored by other DAIT-supported contracts or grants. At U.S. and international clinical sites and pharmacies where DAIT-supported clinical trials are conducted, this initiative will:

  • Perform on-site monitoring of the conduct/compliance with Good Clinical Practices (GCP).
  • Monitor laboratory facilities and procedures for obtaining, testing, and storing clinical research specimens.
  • Train site personnel in GCP and in the policies and procedures established by DAIT/ITN, NIH, FDA, and the HHS Office for Human Research Protections.
  • Recruit and train site monitors.
  • Prepare reports on monitoring findings and training activities.

NIAID Division of Allergy, Immunology, and Transplantation: Clinical Research Administrative Support Group: This initiative will facilitate DAIT's ability to fulfill its responsibilities as a clinical trials sponsor and to comply with NIH and NIAID policies on data and safety monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the clinical trial data. The initiative will also facilitate the protocol development process and associated regulatory processes.

The subcommittee discussed the overall merits of the above three initiatives and found them to be significant in forming a foundation for the clinical research programs with DAIT and endorsed and unanimously approved all three initiatives.

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

Dr. Heilman introduced new Subcommittee member Dr. George Siber, Executive Chairman of Genocea. She also noted three recent or upcoming DMID retirements: Drs. George Curlin in the DMID OD, and Fran Rubin and Robert Goldman in the Respiratory Diseases Branch. Dr. Heilman then referred to the Branch Chiefs/Acting Branch Chiefs in attendance to introduce their respective new hires.

Dr. Heilman reported that two DMID grantees were recently selected to receive a Presidential Early Career Award for Scientists and Engineers, which recognizes scientists who achieve extraordinary accomplishments at an early stage of their careers.

Dr. Heilman then provided a brief, general overview of DMID’s clinical research infrastructure as an introduction to the three clinical research concepts that would be presented to the Subcommittee for their consideration. She provided data on the number and type of clinical trials supported by DMID over the past 5 years, and described the general, more broad-based clinical trial infrastructure that DMID supports (e.g., the Vaccine and Treatment Evaluation Units) as well as the targeted clinical activities (e.g., those dealing with special or unique populations, or strategy-based clinical approaches); DMID’s broad infectious diseases mandate requires the flexibility to respond in a variety of ways. She also noted that DMID partners with other agencies or organizations to achieve some of its clinical goals, e.g., collaborative activities with DHHS. Finally, in follow-up to a Subcommittee discussion at the September Advisory Council meeting, she reported that discussions were still ongoing and evolving throughout the Institute about possible restructuring of the Institute’s clinical trial infrastructure.

Following Dr. Heilman’s remarks three concepts were presented for the Subcommittee’s consideration:

Targeted Clinical Trials to Address Select Viral Infections - The goal of this initiative is to conduct targeted clinical studies (natural history) and/or interventional clinical trials (phase I, II or IV) to address unmet medical needs for select viral infections, and to push forward clinical trial science in the study of these rare/challenging viral diseases by encouraging innovative or adaptive design strategies.

Subcommittee consideration: This initiative will replace the currently active Clinical Antiviral Study Group program (CASG). The Subcommittee questioned the proposed changes to the CASG in light of the program’s success; program staff explained that the new approach would provide support for targeted clinical studies and trials in those research areas identified during a recent external programmatic review as important unmet medical needs. Dr. Heilman noted that other emerging viral threats could be addressed using other contract resources, if necessary. The rationale for the use of the Broad Agency Announcement rather than a more directive request for proposals was discussed as a way to solicit the best and most innovative approaches to address the targeted research areas. Council members unanimously approved the concept.

Targeted Clinical Trials to Reduce the Risk of Antimicrobial Resistance - The goal of this initiative is to support targeted clinical trials to address the growing public health problem of antimicrobial resistance, with a focus on strategies to preserve the use of existing antimicrobials in the areas of greatest drug use.

Subcommittee consideration: The Subcommittee discussion was directed at generating an understanding of how the Broad Agency Announcement mechanism worked, and how the community of offerors would have a role in developing specific protocols that best addressed the needed data to inform the optimal drug use in areas of greatest antimicrobial selective pressure. It was explained that NIAID specifies the targeted disease areas and a series of approaches to drug use and that the community of offerors determines the best approach for the particular disease area that would best inform drug use, and would be a feasible protocol for them to implement. Another discussion took place with regard to how the proposed trials would fit in the context of clinical standards of care. It was explained that NIAID was not proposing standards of care, but rather was supporting trials to generate data that could be used by those who develop standards of care based on evolving evidence. The concept was unanimously approved.

Sexually Transmitted Infections Clinical Trials Group – The goal of this initiative is to provide support for the conduct of clinical trials to evaluate diagnostics, therapeutics, vaccines, and microbicides for the control and prevention of Sexually Transmitted Infections (STIs).

Subcommittee consideration: The discussion acknowledged the importance of the research area and the need to have the capability to evaluate products for the control and prevention of STIs, an area of public health need. Though this concept focuses on domestic capability, the council suggested that international capabilities should be available when needed to address a particular scientific question. Council members unanimously approved the concept for the Sexually Transmitted Infections Clinical Trials Group.

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

Participating members were Christel H. Uittenbogaart (Chair), Robert G. Brooks, Carol A. Carter, Connie Celum, Satya Dandekar, Karen Goldenthal, Maureen M. Goodenow, Daria J. Hazuda, Andrea Kovacs, Judy Lieberman, Louis J. Picker, Susan Swindells, and Mitchell J. Warren. Ex officio members Debbie L. Birx, Nelson Michael, and Ronald O. Valdiserri participated in the meeting, as did Paul Volberding, liaison to the Office of AIDS Research Advisory Committee. NIAID representatives included Carl W. Dieffenbach, Margaret (Peggy) Johnston, Susan Plaeger, and Sheryl Zwerski. Rona Siskind served as executive secretary.

Welcome and Approval of Minutes

Dr. Uittenbogaart welcomed the ARAC members, DAIDS representatives, and guests. She announced that three new ARAC members were in attendance - Connie Celum, M.D., M.P.H., Susan Swindells, M.B.B.S., and Mitchell J. Warren. She presented the minutes of the September 2009 ARAC meeting, and the members approved them with no changes by a hand vote.

Director's Report

Dr. Carl Dieffenbach welcomed the ARAC members, attending DAIDS and NIAID representatives, and other guests. He introduced Christel H. Uittenbogaart, M.D., the new chair of the committee.

New ARAC Members

Dr. Dieffenbach presented brief bios of the three new members of the ARAC.

  • Dr. Susan Swindells is Medical Director of the HIV Clinic at the University of Nebraska Medical Center and the Terry K. Watanabe Professor of Internal Medicine in the Section of Infectious Diseases. She earned her medical degree from the University College in London in 1977 and performed postgraduate training in England and at the University of Washington, Seattle. Dr. Swindells is Director of the UNMC Ryan White Title III Program, the Nebraska AIDS Drug Assistance Program, and the Nebraska AIDS Education and Training Center. As part of the leadership of the AIDS Clinical Trials Group, she brings in depth knowledge and experience of our clinical trials networks to the committee.
  • Mitchell Warren is the Executive Director of the AIDS Vaccine Advocacy Coalition, which uses public education, policy analysis, advocacy, and community mobilization to accelerate the development and delivery of AIDS vaccines and other HIV prevention options. He served as Vice President and Director of International Affairs for The Female Health Company, the manufacturer of the female condom. Mr. Warren studied English and history at the University of Wisconsin-Madison and health policy at the Johns Hopkins University School of Hygiene and Public Health.
  • Dr. Connie Celum is Professor of Global Health and Medicine and Director of the International Clinical Research Center in the Department of Global Health at the University of Washington. Her research currently focuses on clinical trials of biomedical HIV prevention strategies to reduce acquisition and transmission. Dr. Celum has conducted HIV prevention trials and is the principal investigator of a Phase 3 randomized placebo-controlled trial of pre-exposure antiretroviral prophylaxis, featuring Truvada (tenofovir), taking place in Kenya and Uganda. She is a co-investigator and member of the Executive Committee of the NIAID -funded Microbicides Trials Network.

Division Staff Update

Dr. Dieffenbach announced that Scott Proestel, M.D., recently joined DAIDS as the new Deputy Director of the Office of Policy in Clinical Research Operations. Dr. Proestel served for 8 years at the Food and Drug Administration as medical officer in the Division of Antiviral Products. He has experience working with investigators and companies to assess therapeutics in all stages of development.

Budget Update

Dr. Dieffenbach noted that NIAID’s FY 2010 budget of $4.8 billion represents a 2.6-percent increase over the FY 2009 budget. Most NIH institutes and centers received, for FY 2010, increases slightly greater than the NIH budget increase of 2.3 percent. Programs in the Office of the Directors experienced reductions. The new NIAID budget includes a mandated 2-percent increase for non-competing grants. Dr. Dieffenbach stated that, in light of the economic climate, NIAID is taking a conservative approach and protecting the budget in the early part of 2010. It plans to fund at least as many competing research project grants (RPGs) as were funded in 2009. In late 2010 we will likely see an increase in R01 applications when PIs “recycle” their unsuccessful NIH Challenge Grant applications. As a result, success rates will naturally decrease. Because of these uncertainties, NIAID has set its provisional payline at the 8th percentile. This will ensure that high-scoring applications are funded while the budget picture remains uncertain. Paylines will be finalized in the spring.

Most of the $1.11 billion in funds from the American Recovery and Reinvestment Act (ARRA) given to NIAID was used to support RPGs (86 percent). A small amount supported solicited initiatives (RFAs and PAs) and signature projects. Some projects (especially contracts for testing vaccines) have been in support of the national response to the outbreak of H1N1 influenza. NIAID obligated about $551 million of its ARRA funds during 2009 - 936 grant awards overall. Many of those first-year grants are slated for a second year of funding under ARRA.

The availability of one-time funds characterizing the ARRA program likely will lead to a strong “cliff effect” in 2011. The NIH Challenge Grant program, under ARRA, received about 20,000 applications, and only about 440 could be funded. Many of the unfunded applications could be resubmitted as R01s in the 2011 cycle (post-ARRA). In addition, many of the PIs who obtained ARRA-supported grants will re-submit applications for additional funding in 2011. In all, NIAID anticipates, for FY 2011, about 1,000 R01 grant applications beyond the ordinary amount. As a result, the payline for FY 2011 will be strained, and the success rate might become as low as 16 or 17 percent. Dr. Dieffenbach presented recent histories of success rates for NIAID and DAIDS grant programs. Most programs saw a decline in the success rate in moving from FY 2008 to FY 2009. As one example, the success rate for R21 grants decreased from 24 to 20 percent - suggesting a need for new strategies.

Scientific Update

Dr. Dieffenbach reviewed two trials evaluating the power of H1N1 vaccines in HIV-infected people. Both were initiated in the fall of 2009. The first study, P1086 involved 130 pregnant women on HAART who received doses of the Novartis inactivated H1N1 vaccine. Safety and immunogenicity assessments were made after each dose, at delivery, and at 3 and 6 months post delivery. The second study, P1088, involved 150 children between the ages of 4 and 24, who received the Novartis monovalent H1N1 vaccine. The results of both studies will be presented at the CROI meeting in February.

In October, at the International AIDS Vaccine Conference in Paris, Thai and U.S. researchers announced initial results of the Thai Phase III HIV vaccine trial (RV144). The trial tested a prime-boost combination of two vaccines based on HIV strains in Thailand and found a reduction in the rate of HIV infection. The efficacy of the regimen was modest, yet the trial demonstrated that both basic and clinical research serve to determine immune mechanisms, and it provided information for future developments. Meetings to plan next steps continue.

The MDP 301 trial of PRO 2000 microbicide gel, conducted in the United Kingdom produced no evidence that the vaginal microbicide PRO 2000 reduced HIV infection in women. Although the product showed promise in NIAID’s HPTN 035 study, the results were not statistically significant. Based on the results of both studies, it can be concluded that PRO 2000 is safe but does not protect against HIV.

Another disappointment was a CDC trial conducted in Botswana, of Truvada (tenofovir) used as pre-exposure prophylaxis. The investigators hoped to study the efficacy of the drug in reducing the risk of infection in a heterosexual population. However, low incidence at the study site and challenges in retaining participants caused the investigators to discontinue the trial. Nevertheless, they will seek to obtain data on adherence and safety.

In December, the Department of Health and Human Services released new HIV treatment guidelines. The guidelines now recommend that patients at any CD4 count be offered antiretroviral therapy (including those with counts over 500 cells/mm3). Persons who are pregnant or have neuropathy or HBV co-infection should begin therapy.

Dr. Dieffenbach listed additional studies underway, including HPTN 052 (which is evaluating the efficacy of HAART to reduce transmission among serodiscordant couples), iPrEX (Phase III PrEP), START, and more.

NIAID recently formed a unique partnership with the city of Washington, D.C., designed to decrease the city’s rate of new HIV infections, improve the health of HIV infected DC residents and strengthen the city’s response to HIV. The program will (1) identify high risk populations, (2) establish a city-wide data system to track the epidemic and evaluate the impact of the interventions, (3) pilot a research protocol for linking testing, and care treatment, and (4) augment HIV subspecialty care in DC clinics with research protocols.

The Strategic Working Group met in January and discussed (1) opportunities for improving upon and increasing collaborations with PEPFAR and the CDC, (2) microbicides trials, (3) HPTN 065(testing linked to care plus treatment/ TLCplus), and (4) the clinical trials infrastructure. The working group encouraged more outreach to international components of the CDC and applauded and encouraged the microbicides network.

NIAID has held multiple consultations focused on restructuring the infrastructure of the HIV/AIDS and other clinical trials network. Possibilities being explored include the development of a multiple disease clinical research capacity, incorporation of new expertise for expanded infectious disease in the research portfolio, creation of flexibility for expanding and contracting sites, and increasing IRB efficiency. Feedback from stakeholder groups will be collected this year, and an RFA will be developed by the end of the year.

Discussion

Committee members applauded the Washington D.C. partnership project and encouraged expansion of HIV prevention clinical trials into the city. The issue of expanding the networks led to the discussion of whether planned multidisciplinary networks might venture beyond infectious diseases - to other related areas such as aging, cardiovascular health, diabetes, etc. (and involving other institutes). NIAID was encouraged to examine use of the CFAR mechanism as a model for future partnerships.

Update From the Office of AIDS Research Advisory Council

Christel H. Uittenbogaart, M.D., UCLA School of Medicine

Dr. Uittenbogaart reported that the Office of AIDS Research (OAR) Advisory Council (OARAC) met on November 5, 2009 and focused on the following agenda items: an update from the working group for prevention and treatment guidelines, HIV co-infections and co-morbidities in the United States and world-wide, and NIAID priorities for IC collaborations with the HIV/AIDS clinical trials networks to address comorbidities.

A number of NIH institute representatives made presentations on their institute’s priorities with the goal of determining the potential for collaborations between institutes. Presentations included those by the National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The council also received a report from the Implementation Science Workshop.

The OARAC discussions focused on AIDS-related diseases (diabetes, atherosclerosis, osteoporosis, etc.), co-infections (e.g., tuberculosis, hepatitis B and C), the older-age phenotype that results from HIV infection, and challenges in managing older HIV infected individuals.

Dr. Dieffenbach stressed that the OARAC has been extremely helpful in identifying expertise and partners for DAIDS research.

Report of the AIDS Vaccine Research Subcommittee

Louis J. Picker, M.D., Vaccine and Gene Therapy Institute, Oregon Health Sciences University

Dr. Louis Picker reviewed recent work of ARAC’s AIDS Vaccine Research Subcommittee (AVRS), which met on September 15-16, 2009. That meeting focused on:

  • The Thai Phase III vaccine trial.
  • AIDS vaccine design based on mosaic gene sequences.
  • Large-scale efforts to address the neutralizing antibody problem.

To respond to HIV variability, investigators have enlisted various strategies, including the use of mosaic gene sequences, which are in silico generated recombinant genes that optimize coverage of potential epitopes in a population. Mosaic “cocktails” have been applied in monkey models and have produced improvements both in breadth and depth of T cell responses, outperforming vaccines based on either wild-type or consensus sequence genes. Plans are underway to test mosaic gene-based vaccines in clinical trials to see if the improvements observed in monkeys can be duplicated in humans.

A major hurdle in AIDS vaccine research is the development of an immunogen that can induce broadly reactive neutralizing antibodies. Researchers have been attempting to address this challenge for 25 years with little success. In the past several years a number of agencies (NIAID, IAVI, BMGF) have created large consortia to address this problem. Representatives of each of these groups presented how their consortia were organized and summarized their recent achievements. The AVRS recommended that these large collaborative efforts continue to be supported but also recognized the need for funding of this research through smaller investigator initiated research grant mechanisms.

Dr. Picker noted that Satya Dandekar, Ph.D., will be taking over as the AVRS liaison to the ARAC. The next subcommittee meeting is scheduled for February 2, 2010, and will feature a discussion of the Thai Vaccine Phase III trial (RV144).

Program Highlights: Basic Sciences Program

Susan Plaeger, Ph.D., Director, Basic Sciences Program, DAIDS, and Carolyn Williams, Ph.D., M.P.H., Chief, Epidemiology Branch, DAIDS

In providing an overview of the DAIDS Basic Sciences Program, Dr. Susan Plaeger, noted that it supports about 600 active research grants in molecular biology, immunology, mechanisms of latency, epidemiology, HIV modeling, host genetics, gene therapy, and identification of novel targets for intervention. Through contract mechanisms, it supports work in animal models, drug and microbicide screening, reagents, and therapeutic vaccine/drug development and also supports 20 Centers for AIDS research (CFAR) across the United States. Recent funding opportunities include support for research on HIV pathogenesis in women and research on HIV persistence. The Basic Sciences Program addresses the following overarching issues:

  • Early events in HIV transmission and mechanisms of host resistance.
  • Host factors in HIV replication.
  • The immune/inflammatory response to HIV.
  • Mechanisms of HIV latency and persistence.

Dr. Plaeger stressed the continuing need to identify HIV reservoirs in the body and the inability of HAART to eliminate viremia. She highlighted the program’s emphasis on studying HIV persistence and latency, including a series of new grant opportunities. This year will see the release of an RFA for the Martin Delaney Collaboratory: Toward a Cure, a collaboration of interdisciplinary researchers focused on interventions to target HIV reservoirs.

Dr. Carolyn Williams reviewed programs in population-based science. The Epidemiology Branch is dominated by the cooperative agreements of the Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS), and it supports a portfolio of 73 grants. Scientific topics include treatment, co-morbidities, HIV testing strategies and incidence, HIV-2 and HIV subtypes, resistance, dual infection, immune activation, stigma, and statistical methodology. The branch supports intensive observational cohort data collections, as in the domestic MACS and WIHS programs, and lower-intensity data collection, as in the International Epidemiologic Database to Evaluate AIDS (IeDEA) program. Dr. Williams described those programs in detail and emphasized that observational epidemiology is a key to the understanding of epidemics in populations, to the understanding of therapeutic success, and to studies of long-term outcomes.

In discussion, the epidemiology program was encouraged to explore linkages with existing large databases and Dr. Williams noted that the two mentioned, the Veteran’s Administration and Kaiser Permanente, were already included in the North American IeDEA program. She noted that the IeDEA collaboration was an open program and new databases were welcome. It was also suggested that the program interact with the military’s African malaria surveillance program as NIAID explores a multi-disease research approach. She told the committee that IeDEA has begun working with a variety of institutions in Africa, including US DOD, to obtain epidemiologic data on malaria. Dr. Williams was asked about the WIHS study collection of hair samples. She described the WIHS' novel pK studies which capitalize on the long term sequestration of antiretroviral drugs in hair. This allows for measure of long term ARV exposure which the WIHS has shown is a strong predictor of success on ARVs.

Concept Review

Biomedical Prevention of HIV Research Education Initiative

Katharine Kripke, Ph.D., Assistant Director, Vaccine Research Program

This concept has the objective of creating a supportive environment for enrollment in biomedical prevention trials, using evidence-based approaches to educate and engage U.S. populations most affected by HIV and AIDS in biomedical prevention research. This concept is a renewal/expansion and will be funded through a U25 cooperative agreement mechanism. The first-year cost is $1.8 million and the duration is 5 years. There will be one award. The project responds to the need to ensure that the demographics of HIV prevention studies reflect the epidemic and the need to reduce misinformation about vaccine and other prevention research. The program’s predecessor is the NIAID HIV Vaccine Research Education Initiative; this program expands the scope of education beyond HIV vaccine research to include all biomedical HIV prevention research, including microbicide, pre-exposure prophylaxis, and vaccine research.

The ARAC reviewers were supportive of the broader scope of the program and stressed a need to coordinate with NIAID-funded networks/programs and organizations. They encouraged the program to monitor/assess activities to identify best approaches and to ensure that coordination occurs. It was questioned whether or not past efforts have been successful in reducing misinformation, and again program evaluation was encouraged. The difficulty in evaluating/identifying which approaches/activities lead to results was acknowledged. The ARAC members expressed support for the concept, made a motion to approve it, and voted in favor.

NIAID Virology Quality Assurance

Joseph Fitzgibbon, Ph.D., Drug Development and Clinical Science Branch

This concept’s objectives include the following:

  • To provide a quality assurance program for virology laboratories.
  • To standardize and validate new virologic assays.
  • To provide data management and statistical analysis to assess variability and reproducibility of assays.
  • To support additional laboratories.
  • To support quality assurance (QA) programs for assays of viral disease agents other than HIV and related co-infections. (This is a new objective.)

This is a N01 contract mechanism and a renewal. The first-year cost is $2.9 million, and the duration is 7 years. The QA program currently serves more than 100 DAIDS-supported or collaborative research labs in 22 countries. As an example of recent accomplishments, the program evaluated the new viral load platforms Roche Taqman and Abbott M2000. In the future, the program plans to expand the donor program to produce more representative panels for international labs.

The ARAC reviewers were very supportive of the concept. The importance of standardizing assays and reagent panels to ensure objective and transparent assessments of laboratory data was noted. They encouraged the program expansion to include QA for assays of genotypic resistance to integrase inhibitors and fusion/entry inhibitors, QA for genotypic tropism assays, and QA for HCV drug resistance assays and possibly for HPV typing assays. In discussion, Dr. Fitzgibbon noted that the program includes a number of commercial labs. The need to expand the scope of assays to a larger number of viruses was acknowledged particularly given the likely expansion of the clinical trials networks. Members emphasized the need to seek coordination with other programs to avoid duplication of effort. A motion was made to support the concept; members voted in favor.

Dr. Dieffenbach asked the ARAC members to consider areas of focus for upcoming meetings. They made the following suggestions:

  • A broad discussion of microbicide research.
  • Risk assessment in prevention trials.
  • Ideas for integrating networks globally.
  • Update on START pilot status of enrollment, equipoise and ratio of screening to enrollment.
  • New technologies for studying HIV.

VII. Adjournment

The meeting of the Council was adjourned at 4:15 p.m., on Monday, February 1, 2010.

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

3-11-2010
Date
-s-

Marvin R. Kalt, Ph.D.

Executive Secretary

National Advisory Allergy and Infectious Diseases Council

Director, Division of Extramural Activities

National Institute of Allergy and Infectious Diseases

3-4-2010
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 05, 2013

Last Reviewed August 05, 2013