pathogenesis. If we knew what we were looking for, then getting those samples and going through them to try and identify some of the components of the pathogenesis would be a relatively easy task. The mystery is we do not know what we are looking for, so we just look for the parameters that are available to us right now, and so far they have come up short. Senator REID. Has funding been a problem to study this disease? Dr. FAUCI. Well, it has not been a problem. I wish we had more to be able to fund. We have put out a request for applications, and we look forward to the response for that request. If we get good requests, we would be happy to fund as much as the science allows. Senator REID. Thank you, Mr. Chairman. Senator HARKIN. Thank you, Senator Reid. I thank this panel. I am going to follow up with you on this thing. I don't understand all that completely, but perhaps I can get into it and understand it a little bit better. Thank you all very much. We will call our next panel up, if you don't mind, Dr. Raub. I have to break in about 20 minutes. If we do not finish, we will pick it back up at 1:30. Senator REID. Mr. Chairman. Senator HARKIN. Yes. Senator REID. I will come back whenever you say. I have some questions of Dr. Gorden on the next panel. Senator HARKIN. He is on the next panel? Senator REID. Yes. Senator HARKIN. We can go right to that. Senator REID. OK, thank you. QUESTIONS SUBMITTED BY THE SUBCOMMITTEE Senator HARKIN. Thank you very much. There will be some additional questions which will be submitted for your response in the record. [The following questions were not asked at the hearing, but were submitted to the Institute for response subsequent to the hearing:] QUESTIONS SUBMITTED BY THE SUBCOMMITTEE CHILDREN'S VACCINE Question. The Committee has provided funding and encouragement for the development of a Children's Vaccine. This would be one vaccine which would cover seven or eight of the more common childhood vaccines all in one dose. How optimistic are you that such a vaccine can be developed in the relatively near future? Answer. The World Health Organization and the United Nations Children's Emergency Fund articulated the goal of a single, oral, temperature-stable vaccine that would be effective against the major child-killing infections in the world and produce life-long immunity. While this type of vaccine remains an idealistic goal and a challenge to all who work in the field of vaccinology, practical and scientific considerations encouraged that the concept of a "Children's Vaccine" be recast into a "Children's Vaccine Initiative" (CVI). This initiative has as its goal the continued targeted improvement of childhood vaccines. The CVI calls for expanding the front line of existing and emerging vaccine technology within a framework that is both feasible and achievable over the next 10 years. By accelerating the application of vaccine technology, CVI targets vaccines that will require fewer doses, can be given earlier in life, can be combined in novel ways, are more stable, and are effective against a variety of diseases. Each step will continue to facilitate improved immunization of high risk children in all countries. PEDIATRIC CLINICAL TRIAL UNITS Question. Last year the Conference Committee directed an increase for Pediatric Clinical Trial Units. I understand that with this additional funding 37 percent of all clinical trial funding will go to Pediatric Clinical Trial Units. This compares to approximately 1.5 percent of all the AIDS cases being children. Doctor, has funding been skewed too heavily towards the Pediatric Clinical Trial Units? Answer. Basic research on pediatric AIDS continues to be a high priority and we will be placing more emphasis on this critical health problem. Our current research program focuses on efforts to define the means for early diagnosis, timing of transmission of the virus, pathogenic mechanisms involved in pediatric research, and the roles of immune response in protection or delay of clinical progression. By way of background, the level of funding for pediatric AIDS clinical trials has increased markedly over the last several years in response to the changing demography of the disease. As a result of the increase in pediatric AIDS clinical trials, more treatment protocols are now being sponsored. Despite this progress, the recent congressional earmark to double the amount of resources committed to pediatric AIDS clinica trials causes us some concern because of the vastly disproportionate level of effort that would exist between pediatric and adult clinica trials. Specifically, pediatric AIDS cases represent approximately 1.7 percent of all reported AIDS cases. Currently, 11.8 percent of all patients enrolled in AIDS clinical trials are pediatric patients. With the earmark, approximately 40 percent of all AIDS clinical trial resources will be devoted to pediatric populations. We are concerned that since sufficient additional funds were not provided to finance the earmark, on-going research efforts in vaccine and drug development, epidemiology and adult clinical trials will need to be reduced. Of particular concern is the increasing trend to divert scarce research dollars for health care needs. We agree that a certain level of ancillary services are required to ensure that pediatric populations are able to participate in clinical trials. However, these ancillary services should be commensurate with the level required to ensure that pediatric patients may participate in trials rather than providing the full range of health care coverage. We will continue to confront the problem of pediatric AIDS by supporting an extensive program of treatment and epidemiologic research of HIV in children. While acknowledging the importance of this critical health problem, we should recognize that resources are finite and an appropriate balance needs to exist among pediatric and adult clinical trials, vaccine development and basic research. Question. We often hear that AIDS research that is devoted to adults has benefits for children. Is the reverse true? Answer. Yes. Studies that shed light on the prevention of infection from one infected person to another, such as the protocol designed to limit the spread of infection from an infected mother to her fetus or infant, will be of benefit to both children and adults. Moreover, these studies will also allow us to gather data on how certain drugs, such as zidovudine, affect pregnant women. Finally, studies that look at the role of compounds such as immunoglobulin in preventing additional infections for HIV-infected children may have implications for preventing infections in adults. AIDS Question. Last year we discussed the possibility of developing an AIDS vaccine. I understand that encouraging test results of an AIDS vaccine have occurred with monkeys, and that the FDA has approved the sixth AIDS vaccine for human testing. Dr. Fauci, what is the status of developing an AIDS vaccine for general use? Answer. Recent research findings in animal model systems are showing promise that the development of a safe and effective vaccine for HIV infection is feasible. Results from several research groups have demonstrated protection in monkeys vaccinated with SIV vaccines and then challenged with SIV, and protection in chimpanzees vaccinated with HIV vaccines and challenged with HIV. In some experiments, animals were protected from infection by heterologous SIV strains, that is, virus strains that are different from the vaccine strain. These studies increased optimism that the extensive amount of virus variation, which is common to both SIV and HIV, could be overcome by broadly reactive vaccines. Because SIV and HIV are so closely related and produce very similar types of disease, these studies provided hope that scientists may ultimately create an effective HIV vaccine, a possibility that was considered to be much more remote until last year. The HIV vaccines are being considered not only for protection of uninfected individuals, but for slowing the progression of disease in HIV infected asymptomatics, and for prevention of perinatal transmission from HIV-infected mothers to newborns. Question. I understand that over 55 drugs are being tested for use in AIDS treatments. Do you expect that new treatments will be developed in the near future? Answer. Significant headway in AIDS drug development is being made. In 1990, three new anti-retroviral agents entered phase I clinical trials: 3'-fluorothymidine (FLT), hypericin, and tetrahydro-imidazo (4,5,1-jk) (1,4)-benzodiazepin-2(1H)- thione (TIBO). One of these, FLT, was discovered by the NIAID funded National Cooperative Drug Discovery Groups (NCDDGs). A novel anti-tat inhibitor recently identified by a NCDDG will be in a clinical trial soon. This is a particularly interesting drug that blocks production of HIV from cells already infected by HIV and therefore holds the possibility of delaying or halting disease progression. Two other NCDDG-discovered therapies are anticipated to enter clinical trial within the next year. At least six others are in earlier stages of preclinical development. There is every reason to expect that additional new and novel treatments will continue to arise as a result of concerted efforts directed to find agents active against critical viral and cellular targets, such as reverse transcriptase, HIV protease, regulator proteins such as tat and rev. Basic research on other targets as well as the application of gene therapy to the treatment of HIV infection are also of high priority to the NIAID. Question. How many of the AIDS vaccines are now in clinical trials? Answer. Currently, seven vaccines are in clinical trial in uninfected volunteers, and six vaccines are being evaluated in HIVpositive asymptomatic volunteers. These preliminary studies are addressing the safety and ability of the vaccine to induce immune responses. The goal of these first studies is to obtain comprehensive immunologic analyses on each candidate, and to compare these data to comparable animal model studies. In addition, there are currently several other candidate vaccines in preclinical development, and it is anticipated that a number of these will enter clinical studies in 1991. LYME BORRELIOSIS Question. Doctor, I understand that it is relatively easy to diagnose Lyme Disease if it is detected in its very early stages and that doctors across the country now can make successful diagnoses. The problem, however, is when the disease has progressed for awhile, the diagnosis is more difficult. What is the status of our ability to diagnose Lyme Disease and do you feel that the disease is adequately understood by all practicing physicians across the country? Answer. Although early treatment of Lyme borreliosis has a high success rate, early diagnosis is often problematic for many of the same reasons that hinder effective diagnosis of cases of Lyme borreliosis that have progressed for months or years. Lyme borreliosis at any state of progression can be difficult to diagnose because of the wide and variable range of symptoms exhibited by patients and, therefore, can easily be confused with many other pathological conditions. In addition, patients vary greatly with respect to their immune response to the causative agent and to the extent to which the causative agent is present in the patient. Thus, the variability in the type and extent of immune response and the presence of antigen, or other remnants of the causative agent, in patients make it particularly difficult to develop an effective diagnostic test. There are many diagnostic tests currently available in the marketplace but none of them are regarded as highly reliable. Physicians often rely on the results of diagnostic tests to confirm a diagnosis of Lyme borreliosis. Therefore even the physicians with the most experience with Lyme borreliosis currently do not adequately understand the disease. In fact, no one does. That is why we are aggressively supporting and encouraging research on Lyme borreliosis. The NIAID and the NIAMS have issued Requests for Application for further research on the diagnosis and therapy of Lyme borreliosis. In addition, NIAID and NIAMS have co-sponsored a state-of-the-art Workshop on the "Diagnosis and Therapy of Lyme Disease" which was held in March of this year. The purpose of this Workshop was to aid physicians in making decisions, using currently available knowledge and technology, regarding diagnosis and therapy when faced with patients that may have Lyme borreliosis. REPRESENTATION OF WOMEN IN CLINICAL TRIALS Question. Dr. Fauci, I understand that approximately seven percent of those involved in your Institute's clinical trials are women, and I understand further that you do want to increase that participation level. What goal do you have for enrolling women in your Institute's clinical trials? Answer. Our goals are to ensure that we adequately address the high priority scientific questions specific to HIV disease in women, and to have women included in trials to the degree which reflects the pattern of the disease in the general population. In response to the low enrollment of women onto AIDS Clinical Trials, NIAID has taken the following action: Fostered the establishment of the Women's Health Committee, a In 1990, supplemental funds were awarded to 12 existing |