6. Report of the Joint Meeting of AIDS Subcommittee, NAAIDC, and AIDS Research Advisory Committee NIAID

John Y. Killen, M.D., Director, DAIDS

The meeting, which was held in the Natcher Conference Center on the campus of the National Institutes of Health, was chaired by Dr. Marian R. Neutra, chairperson of the AIDS Research Advisory Committee (ARAC).

• Report from the Director
  
  Dr. Killen welcomed everyone to the meeting, particularly Ms. Saint Cyr and Dr. Barton Haynes, who are new members of Council.

• Budget Update
  Dr. Killen provided an update on the FY 1999 budget for NIAID and explained the difference between the payline and success rate. He announced that DAIDS had awarded three contracts since the September meeting: one for a statistical and coordinating center for the Women and Infants HIV Transmission Study, one for the HIV Research and Specimen Processing Laboratory's chimpanzee labs, and one for the renewal of the Immunology Quality Assessment Program.

• Looking Ahead: A Framework for the Year 2001
  For the rest of the day, the Committee discussed the division's thinking with respect to scientific priorities for the FY 2001 budget. Dr. Neutra asked Dr. Killen to clarify how NIAID's planning process and that of the Office of AIDS Research interface. Dr. Killen said NIAID and the Committee are very much involved in OAR's process, and Dr. Nathanson described OAR's budget process.

• Basic Sciences Program — Dr. Carl Dieffenbach

  Dr. Dieffenbach said the Division's grant portfolio is quite large. Since 1993, the Division has increased this portfolio by 50 percent in terms of both dollars and numbers of grants to build "a very strong basic research engine that is driving the science of AIDS." NIAID's budget represents 50 percent of the total AIDS budget. He reviewed major scientific developments and current research priorities in the basic science area.

• Vaccine Research and Prevention — Dr. Peggy Johnston

  Dr. Johnston reviewed recent scientific highlights, such as the elucidation of the HIV envelope. As for work in vivo, transgenic models have advanced and in the area of primate SIV and SHIV models, a growing number of vaccine concepts are affording some protection. Finally, the gp120 efficacy trial has begun in humans.
  Scientific challenges include the need for more and better animal models and for defined HIV serotypes, the lack of information about the effect of HLA and HIV diversity on vaccine efficacy, and the need for more information on the HIV envelope.
  NIAID's goals for the next two years include continuing support for the innovative research program, widening all stages of the vaccine pipeline, and strengthening collaborations with developing countries.

• Therapeutics Research — Dr. William Duncan

  • Adult HIV Research Program
    At the forefront of the research agenda is the development of more potent and more easily tolerated drugs and HAART regimens. New and better therapies are needed to minimize viral replication and tissue burden. Also needed are new drugs that are more tolerable, require fewer doses, and have fewer side effects. New protease inhibitors in the pipeline may have new resistance profiles that will help overcome current class-specific resistance. Drugs that eliminate the virus from tissue reservoirs and infected cells are also needed as are drugs for new targets, such as integrase, TAT, and fusion receptors.
    The long-term effects of antiretroviral therapy must be assessed since people will be treated for long periods, perhaps life. Dr. Duncan spoke of the need to focus on the pathogenesis of HIV-1, particularly which host and viral factors influence patients' responses to these therapies.
    The Adult Therapeutics Clinical Trials Program is being recompeted. NIAID plans to award a contract on January 1, 2000. Dr. Duncan discussed the Hemophilia Initiative of the Adult Therapeutics Clinical Trials Program. NIAID plans to convene a Task Force by early summer to review the unique scientific needs of HIV-infected hemophiliacs. The results of this review will be reported at the September meeting.

  • Pediatric/Perinatal Research Program
    The number of pediatric AIDS cases in the United States peaked in 1993. Dr. Duncan attributed the subsequent fall to the results of the Pediatric ACTG study, which demonstrated that treatment of pregnant mothers and infants with AZT reduced perinatal HIV transmission. Research priorities include identifying acute HIV infection in infants and adolescents infected perinatally and developing aggressive treatment for this population. The immunologic reconstitution potential of pediatric populations on HAART therapies is also important. Infected children have highly active thymuses, and researchers hope to harness their HIV-specific immune response. Information is needed on the transmission rate in the U.S. and the nature of the international links and collaborations needed to develop a global agenda.

• Crosscutting Themes and Issues — Dr. John Killen

  Dr. Killen discussed four crosscutting issues: international activities, pediatrics, the Centers for AIDS Research (CFARs) program, and the clinical trials operations. Important issues related to international programs include the need to establish and foster trust through long-term relationships.
  On the topic of pediatrics, Dr. Killen stressed that it is time for NIH to review its entire pediatrics research portfolio. Dr. Phair stressed the need for input from the obstetrics community, since they have not been sufficiently invested in this effort and ACTG has never come to grips with how to fund and manage prenatal trials.
  Dr. Killen said NIH will launch an external review to determine what form the CFARs program should take. Dr. Neutra said this review should identify CFAR activities that are not ongoing elsewhere. Dr. Rinaldo noted that more holistic and broad-based centers are needed and did not think CFARs are under as much pressure as those in other NIH programs to get the maximum value from each dollar they receive. Dr. Ellner noted the need to connect the CFARs with one another as well as other institutions.