SPECIFIC PROJECTS UNDERTAKEN Dr. YOUNG. Specific projects we will undertake include: the followup and evaluation of blood donors who are found positive by the HTLV-III screening test to determine the medical significance of a result of an individual and the risk associated with blood donations from persons who have developed antibodies to HTLV-III; a study of the impact of additional tests for HTLV-III virus and other retrovirus on the safety of the blood supply-this will be extremely critical; and a study to determine whether HTLV-III is present in feces to investigate transmission in animal models. We will also be involved in additional quality control monitoring of test kits for HTLV-III; review and approval of second and third generation tests for AIDS, and development of adequate methods for collecting and analyzing adverse reactions reports associated with drugs and biologics. We are extremely pleased to have this opportunity to speak to your committee, a committee I usually do not have the privilege of addressing. I will be delighted to provide information in answer to questions or any other followup information we could provide to do our part with the entire Government and private sector in meeting the needs to overcome this most significant and greatest health priority in the Nation. Thank you. Senator WEICKER. Thank you very much, Dr. Young. I appreciate your willingness to appear before the committee. We will be working closely with Senator Cochran. It is my understanding, Dr. Mason, that the moneys already appropriated, or those contemplated to be sent to the committee, include the clinical trials of four drugs in the sense of those drugs being used to stop the shedding process or the propagation of AIDS. Again, I am not a scientist. I am merely expressing my layman's knowledge. If I am not mistaken, somebody can correct me, there are really two tracks we are talking about here. That is one of vaccine Dr. MASON. That is correct. Senator WEICKER [continuing]. Which is the long-range solution to the problem, and the other track being that of the use of drugs in order to halt this process; am I correct? Dr. MASON. That is correct. There are two related approaches, one that deals with the discovery, the preparation, the making generally available a vaccine which would allow us to immunize people prior to their coming in contact with the virus. That is proceeding down one track. There is a separate track, with ongoing communication between them looking at chemotherapy. This track will specifically attack the virus after the person has been infected. As Dr. Wyngaarden mentioned, the therapy track bifurcates into two parts because one must lead to something that will destroy the virus in the body. Since these patients may have an immune system which has been destroyed by the virus, you not only have to get rid of the virus but there has to be a way to restore or enhance the immune system, but these drug development activities are proceeding along two major tracks. agreed to by telephone as all parties work together to closely monitor the progress of patients under study. FDA scientists in FDA laboratories on the NIH campus collaborate with other groups involved in AIDS research. They are participating in the in vitro screening of antiviral drugs and immune stimulators and in the evaluation of patients on experimental treatments at the NIH Clinical Center. This integration of FDA into the total AIDS effort guarantees that, as was the case with the HTLV-III antibody test, any promising product will get rapid regulatory review and become generally available in the shortest possible time. References 1. Kuritsky J: Results of human T-lymphotropic virus type-III test kits reported from blood collection centers-United States; April 22-June 16, 1985. Proceedings of Workshop on Experience with HTLV-III Antibody Testing, sponsored by FDA, NIH and CDC, July 31, 1985. 2. Allen JR, et al.: HTLV-III antibody screening in a blood bank: laboratory and clinical correlations. Proceedings of Workshop on Experience with HTLV-III Antibody Testing, sponsored by FDA, NIH and CDC, July 31, 1985. 3. CDC: Prevention of acquired immune deficiency (AIDS): Report of inter-agency recommendations. MMWR 1983; 32:101-104. 4. Schorr JB, et al.: Prevalence of HTLV-III antibody in American blood donors. N Engl J Med 1985; 313:384-385. 5. CDC: Testing donors of organs, tissues, and semen for antibody to human T-lymphotropic virus type-III/lymphadenopathy-associated virus. MMWR 1985; 34:294. 6. Jason J, et al.: Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. JAMA 1985; 253(23):3409-3415. 7. CDC, FDA, ADAMHA, NIH, HRSA: Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the virus causing acquired immunodeficiency syndrome. MMWR 1985; 34:5-7. 8. CDC: Acquired immune deficiency syndrome (AIDS): precautions for clinical and laboratory staffs. MMWR 1982; 31:577-580. 9. CDC: Acquired immunodeficiency syndrome (AIDS): precautions for health-care workers and allied professionals. MMWR 1983; 32:450-452. 10. CDC: Current trends: update on acquired immune deficiency syndrome (AIDS)—United States. MMWR 1982; 31:507-514. 11. CDC: Revision of the case definition of acquired immunodeficiency syndrome for national reporting-United States. MMWR 1985; 34:373-375. 12. Mitsuya H, et al.: Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science 1984; 226:172-174. 13. Goldsmith MF: Not there yet, but on our way in AIDS research, scientists say. JAMA 1985; 253(23):3369-3383. 14. McCormick JB, et al.: Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes. Lancet 1985; ii(8416):1366-1369. 15. Mason JO: Statement before the Subcommittee on Health and the Environment, Committee on Energy and Commerce, U.S. House of Representatives, July 22, 1985. 16. Unpublished report of AIDS Antiviral Agent Workshop, NIH, June 3, 1985. NIAID, Bldg. 31, Rm. 7-A-49, 9000 Rockville Pike, Rockville MD 20205. 17. Lane, et al.: Use of interleukin-2 in patients with acquired immunodeficiency syndrome. J Biol Resp Mod 1984; 3:513-516. SPECIFIC PROJECTS UNDERTAKEN Dr. YOUNG. Specific projects we will undertake include: the followup and evaluation of blood donors who are found positive by the HTLV-III screening test to determine the medical significance of a result of an individual and the risk associated with blood donations from persons who have developed antibodies to HTLV-III; a study of the impact of additional tests for HTLV-III virus and other retrovirus on the safety of the blood supply-this will be extremely critical; and a study to determine whether HTLV-III is present in feces to investigate transmission in animal models. We will also be involved in additional quality control monitoring of test kits for HTLV-III; review and approval of second and third generation tests for AIDS, and development of adequate methods for collecting and analyzing adverse reactions reports associated with drugs and biologics. We are extremely pleased to have this opportunity to speak to your committee, a committee I usually do not have the privilege of addressing. I will be delighted to provide information in answer to questions or any other followup information we could provide to do our part with the entire Government and private sector in meeting the needs to overcome this most significant and greatest health priority in the Nation. Thank you. Senator WEICKER. Thank you very much, Dr. Young. I appreciate your willingness to appear before the committee. We will be working closely with Senator Cochran. It is my understanding, Dr. Mason, that the moneys already appropriated, or those contemplated to be sent to the committee, include the clinical trials of four drugs in the sense of those drugs being used to stop the shedding process or the propagation of AIDS. Again, I am not a scientist. I am merely expressing my layman's knowledge. If I am not mistaken, somebody can correct me, there are really two tracks we are talking about here. That is one of vaccine Dr. MASON. That is correct. Senator WEICKER [continuing]. Which is the long-range solution to the problem, and the other track being that of the use of drugs in order to halt this process; am I correct? Dr. MASON. That is correct. There are two related approaches, one that deals with the discovery, the preparation, the making generally available a vaccine which would allow us to immunize people prior to their coming in contact with the virus. That is proceeding down one track. There is a separate track, with ongoing communication between them looking at chemotherapy. This track will specifically attack the virus after the person has been infected. As Dr. Wyngaarden mentioned, the therapy track bifurcates into two parts because one must lead to something that will destroy the virus in the body. Since these patients may have an immune system which has been destroyed by the virus, you not only have to get rid of the virus but there has to be a way to restore or enhance the immune system, but these drug development activities are proceeding along two major tracks. Senator WEICKER. I understand. It is my understanding in that area of drug testing that the budget contemplates or there is actually ongoing now or will shortly be ongoing clinical trials for four of these drugs, is that correct? Dr. MASON. Is that right, Dr. Wyngaarden? Dr. WYNGAARDEN. Yes; you are talking about the most recent identification of new initiatives. The NCI and NIAID will develop and carry out an elaborate plan for the development and testing of drugs for the treatment of AIDS, as well as opportunistic infections. The plan now is to undertake four such studies within the next year. That depends, of course, upon the rate of development of new opportunities, but in each of those initiatives, there is a great spectrum of work anticipated starting with the testing of chemicals for antiviral activity, as inhibitors of the enzyme specifically found in this virus, the testing, carrying this into phase I, II, and III studies. We have estimated costs for the whole process and the plan is and hope is to be able to do that on four agents. Senator WEICKER. Then the question is from an operations standpoint from an appropriations standpoint-are there additional drugs which you or any of your colleagues would like to see clinically tested at this juncture? If so, I gather there is pretty much a rule of thumb as to each one of these trials' costs. Obviously, there would be a financial impact on what it is you would need in appropriations. Dr. WYNGAARDEN. I think if you would like more specific information on that, Dr. DeVita, in whose Institute these drugs are first tested, might say a few words on that. Senator WEICKER. Again, let me repeat my question, which I know you understand, Dr. DeVita, is the number four being set by our appropriation or indeed is the number four being set by your scientific evaluation as being the appropriate number right now? Is it being set by me? Is it being set by OMB or being set by you, the scientists, this number four? I obviously have a distinct bias that it should be set by you, not by me or anybody else. Dr. MASON. In the President's amended budget that includes the $126 million for fiscal year 1986, there was an expansion of effort to develop antivirals which brings NIH up to the level of four, which was their request. In the request for the additional money I mentioned that has not yet come through the system, we have taken into consideration that there well may be additional agents. In fact, NIH has tested over 100. Of course, all of those are not showing promise. We do not want to be in a position where we cannot move ahead with dispatch on any reasonable number. I don't think four is necessarily sacred or holy, it is where we were when that budget was put forth. Now things have changed. I should also mention, in addition to what is happening at NIH, there is much interest in the private sector. It is important that we do everything we can to enhance and encourage so that this work does not become just a Federal effort. It must be cooperation between the pub lic-private sectors. Dr. Young has outlined things he has been doing to facilitate private sector contributions. The four are those that NIH is planning to work on. We want, however, to enhance that through the private sector and enhance our own ability to move ahead with more drugs. Senator WEICKER. Thank you very much, Dr. Mason. Dr. DeVita, would you like to expand? Dr. DEVITA. Yes, Senator. Actually the number four was set by us as the number of drugs that we can get into clincial trial very quickly at the present time, although there are more than four candidate drugs. Our plans include starting with four, because we never complete testing in one year on a set of drugs like these. There is a carryover of about two drugs per year, so the number will expand. Two drugs are already in their early stages of testing and ready to go into later stages of testing. So we need to adjust two more drugs in our expansion. I might add that we do have several very interesting candidate drugs. Senator WEICKER. I have one more question, one broad question before those asked by Senator D'Amato. I received from a member of the press the following question: How can casual contact be ruled out when the virus has been isolated in tears and saliva? I was going to ask the question. I want to go back to your testimony, Dr. Mason, prepared testimony, where you said: We know now that infected mothers can transmit the virus to their babies across the placenta and likely through breast milk. Although the AIDS virus has been isolated from human saliva and tears, there is no evidence transmission has occurred through these routes. There has not been a single case of AIDS reported to us in family members of AIDS patients, except for sexual partners and children born to infected women. In studies of over 300 household contacts, not one person, other than sexual contact or child born to an infected mother, became seropositive or developed AIDS as a result of living with AIDS patients. Studies of more than 1,472 health care workers who have close contact with very ill, often hospitalized, AIDS patients, not one has developed AIDS or become seropositive as a result of contact with patients other than through needle stick injury. I would like you and anybody else who cares to respond to this very important question, probably the most important question, the transmissibility of AIDS, and I might as well start out with the question given through the Chair, how can casual contact be ruled out since the virus has been isolated in tears and saliva? Dr. MASON. I won't repeat what you have already read back from my testimony. It was included in the testimony after careful review with all the people here, including Dr. Fauci and Dr. DeVita. I wanted to be sure we all agree 100 percent with the carefully worded statements. I will say again there is no evidence for casual transmission of AIDS from person to person. It is based upon studies that were summarized in my testimony. Coming back to tears and saliva, if virus is present in high quantity in blood, one would almost assume that you could find virus at some time or another in other body fluids. In other words, when our investigators found virus in saliva and tears, this did not surpise us. We |