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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.
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.
How many of the AIDS vaccines are now in clinical
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.
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
have limited study accessibility and protocol compliance of
Question. Why shouldn't it be closer to the percentage of women in the general population?
Answer. We fully agree that the percentage of women in all trials should reflect the demographics of the disease seen in the general population. It is important to note that we have a relatively small improvement to make in this regard since, overall, 6.2 percent of participants in ACTG studies are women, while women represent 9.6 percent of AIDS cases as reported by the Centers for Disease Control.
Question. Dr. Fauci, we are aware that the profile of the AIDS epidemic is changing and that the disease is being seen more and more in minorities, women, children, and intravenous drug users. We also understand that heterosexual transmission is increasing. What is your Institute doing to respond to this change in the AIDS epidemic?
Answer. The NIAID has targeted minority recruitment in its epidemiology cohorts whose participants have not traditionally been minorities. In addition, in the current recompetition of the Multicenter AIDS Cohort Study and San Francisco Men's Health Study, the NIAID will study the issue of access to medical care. Specifically, the investigators will look at access for minority members of the cohort, which will enable them to examine any differences they may find in access to care between minorities and other individuals enrolled in the study.
The NIAID also currently sponsors several large epidemiology studies which research questions related to both the natural history and heterosexual transmission of HIV in women. Each of these cohorts continues to recruit participants and collect data. The Women and Infants Transmission Study addresses issues related to perinatal transmission, the effect of pregnancy on HIV disease, and the effect of HIV on pregnancy outcomes. The Heterosexual HIV Transmission Study looks at transmission in discordant couples and, prospectively, at women at high risk for HIV infection. The Newark Perinatal Study is designed to address the natural history of pregnancies in women infected with HIV compared with that in uninfected women. Over 50 percent of the women enrolled in all of these studies are of minority background.
The NIAID is currently planning to expand studies of the progression of HIV disease in women. In order to expand data collection and analysis as quickly as possible, a two-stage approach is currently being developed.
The first stage will include short-term projects that can be initiated during FY 1991 and continued during FY 1992 to collect and analyze data that already exists in women's health clinics and to analyze data from existing cohorts for gender differences.
In stage two, the results of these short-term projects will provide the foundation for the design of a long-term study of a full cohort of women, which is projected to begin late in FY 1992. The NIAID has recently begun working with other PHS agencies on this initiative. A study group will draft a protocol to help facilitate
this future collaboration by utilizing the specific capabilities of the various PHS agencies.
RECRUITMENT AND RETENTION OF SCIENTIFIC STAFF
Question. Dr. Fauci, have you encountered difficulties in recruiting and retaining staff because of salaries? Will the Senior Biomedical Research Service help to solve that problem?
Answer. In the past, our Institute has encountered difficulties in recruiting and retaining staff. In the case of retention, some of brightest and most productive scientists had been lured to private industry or academia, where salaries have tended to be higher than the government could offer.
The Senior Biomedical Research Service will, to some extent, help solve some of these problems. Specifically, it will be a very valuable tool for recruiting and retaining scientists at the very highest levels in our intramural program, and to some lesser extent in our extramural programs. The SBRS will be utilized to provide a higher rate of pay for a number of our most senior intramural scientists and a few extramural scientists. This will obviously provide us with the very means for providing more competitive salary levels, and thus help to narrow somewhat the wide differential between their current salaries from those available outside of Government.
AIDS VACCINE DEVELOPMENT
Question. Dr. Fauci, could you bring us up to date on the status of AIDS vaccine development. Can you predict when you may have an effective vaccine?
Answer. Thirteen vaccines are in clinical trials world-wide. About half of the trials are being conducted in uninfected people and the other half are being conducted in the infected population. More candidate AIDS vaccines are being developed, more basic research is being done on AIDS, and as a result of these activities, the time frame for developing an effective AIDS vaccine is being shortened. However, I can not give you a definite date.
Question. Dr. Fauci, we have heard that the incidence of asthma is increasing and further, that mortality due to asthma is increasing, particularly in inner-city populations. What is your Institute doing to address this problem?
Answer. We have been very concerned about the increase in asthma morbidity and mortality rates, especially after a period of several years of steady decline. In response to that concern, in February, 1991 we launched the National Cooperative Inner-City Asthma Study. The study will be conducted by eight universities located in Detroit, Cleveland, Chicago, St. Louis, Washington, D.C, Baltimore and New York City. The study is to be conducted over a four-year period and is specifically focused to identify factors contributing to the increased incidence of asthma and will enable us to develop modalities to reduce recurrent asthmatic episodes and asthma-related deaths among inner city Black and Hispanic children. In the initial