If you are interested in knowing whether or not you have antibody to HTLV-III, see your physician or [insert name and location of other testing site]. Information for Persons Who Have a Positive Test for HTLV-III Antibody [To be used in conjunction with the pre-donation information which should be offered again with the test results] A positive HTLV-III antibody test does not always mean that a person has been infected by the virus which causes acquired immunodeficiency syndrome (AIDS). Positive tests in blood and plasma donors may be caused by other things, and that is why a follow-up medical evaluation is important in order to get a better understanding of the meaning of your test results. Your doctor is in the best position to decide what additional tests, if any, need to be done. It is important that you have as open and frank a discussion as possible regarding any possible exposures that you may have had to the virus, so that your physician can make the best evaluation. Until your doctor has made a medical evaluation, it is best to be cautious, even though you have no symptoms, and to assume that you may have been exposed to the virus, that you may be contagious, and that you might unknowingly spread the virus to others. You will want to take responsible steps to prevent the possibility of spreading the virus to other people, especially your family and close contacts. Do not donate blood or plasma, sperm, body organs, or other tissues. You should let your doctor and dentist know that you have a positive HTLV-III antibody test so that they can do their best in caring for you and in preventing spread of the virus. Limit your sexual contacts, and be frank with your sexual partner(s) about steps you are taking to prevent the spread of the virus. Using a condom may help in this regard. Sexual practices in which exchange of body fluids such as semen takes place should be avoided. Virus has been found in saliva of some infected people, and it is possible that it could be transmitted by open-mouthed, or "French," kissing and by oral sex. There is no evidence that the virus can be spread through casual kissing or other casual social contacts such as hugging. Such contacts with other people at work or in the community do not need to be modified. Toothbrushes, razors, or other implements that could become contaminated with blood should not be shared. If you are a drug user: limit your drug use do not let others use needles you have used and do not use someone else's needles do not leave your "works" around where others might pick up needles If you are a woman with a positive antibody test or the sexual partner of a man with a positive antibody test, it would be advisable to avoid pregnancy or to postpone pregnancy until more is learned. Some infants have developed AIDS from their infected mothers. FOOD AND DRUG ADMINISTRATION DRUG BULLETIN, OCT. 1985, VOL. 15, No. 3 Message from Secretary Heckler Over the past two years, scientists at the National Institutes of Health and others in France have identified the virus that causes AIDS and have developed an antibody-screening test for donated blood. Surveillance by the Centers for Disease Control continues to assess the extent of this growing public health problem and enables the Public Health Service to issue recommendations to health professionals to prevent the spread of this deadly disease. In addition, FDA is encouraging research on drugs and biologics to fight both the virus and the opportunistic infections associated with AIDS. We have accomplished much in a short time. Yet AIDS continues to spread and the urgency of our educating both health professionals and the general public about this disease increases, as does the necessity of funding research to develop medical treatments and a vaccine for AIDS. I pledge that this effort will continue to be HHS's number one priority. I join Secretary Heckler in recognizing the urgency of finding ways to contain the spread of AIDS and to make available treatments for those stricken. As with the speedy licensing of test kits for screening blood for antibodies to HTLV-III, FDA is giving highest priority to AIDS-related drugs and biologics. We are providing research incentives through our Orphan Products Development Program and are working closely with manufacturers submitting plans for clinical studies. We also make certain drugs available for "compassionate" or "treatment" use while they are under study. This special issue of the FDA Drug Bulletin summarizes current knowledge about HTLV-III and efforts to prevent its spreading. It augments my previous "Dear Doctor" letter of March 8, 1985. Our publications will continue to keep health professionals informed of progress on AIDS. Sincerely yours, Rank & Young Frank E. Young, M.D., Ph.D Progress On AIDS The identification of the virus responsible for acquired immunodeficiency syndrome (AIDS) has made possible an effective blood antibody screening test and the updating of the AIDS case definition. This causative virus has been named human T-lymphotropic virus type III (HTLV-III) by researchers at the National Institutes of Health (NIH) and lymphadenopathy-associated virus (LAV) by French researchers at the Pasteur Institute. An intensive research effort is under way to find drugs and therapeutic biologics and a vaccine that could be used to treat or prevent the development of this generally fatal disease. Blood Supply Safer Use of screening tests for HTLV-III antibody on donated blood and plasma is successfully preventing the virus responsible for AIDS from entering the blood supply. Conferees at a July 31, 1985, workshop Bethesda, Md., cosponsored by the National Institutes of Health (NIH), FDA and the Centers for Disease Control (CDC), heard that blood and plasma collecting facilities have begun routine testing for this antibody and that all blood found to be reactive must be discarded. At the workshop, representatives from the American National Red Cross, the American Association of Blood Banks, the Council of Community Blood Centers, the Greater New York Blood Program and the American Blood Resources Association agreed that the tests are effective in protecting the public from receiving blood containing HTLV-III. FDA reported data from a survey of more than 1.1 million units of blood collected and tested for HTLV-III antibody by 155 centers of the major blood organizations through June 16, 1985.1 Of this total, 2831 units (0.25%), or about 1 in 400, were reported to be repeatedly reactive for antibody using the licensed enzyme-linked immunosorbent assays (ELISA or EIA) originally developed by NIH scientists. The pattern of positive tests varied slightly in different regions of the country and according to the manufacturer's test kit used. This frequency of repeatedly reactive donors was consistent with the data obtained in clinical trials conducted prior to the licensure of the three manufacturers' reagents. CDC and the Atlanta Region of the American Red Cross reported data from testing more than 51,000 blood donors of whom 0.23% were repeatedly reactive. Of 106 repeatedly reactive units, 34 (32%) were strongly reactive and these correlated highly with both positive Western blot tests (94%) and positive culture for HTLV-III (56%). By contrast, in 220 donors whose tests were initially reactive but subsequently negative, as well as in a random sample of 50 donors with completely negative tests, none had a positive Western blot and none had a positive virus culture. While donors with repeatedly reactive tests are equally distributed between males and females, those with strongly reactive tests that correlated closely with positive Western blot and virus culture results were more apt to be male. Of repeatedly reactive donors interviewed, 89% of those with strongly reactive tests were found to have identifiable risk factors for HTLV-III infection, while none of those with weakly reactive tests had risk factors. Thus, of the approximately 3 in 1200 blood donors found to be repeatedly reactive, about 1 in 1200 will likely be infected with HTLV-III, while about 2 in 1200 will probably be representative of nonspecificity in the test rather than infection. The reason for this nonspecificity is unknown but probably represents, at least in part, the effect of antibody directed against the human cells used to grow the virus in producing test reagents. To measure test sensitivity, antibody tests and virus isolation attempts were made on blood samples from high-risk persons attending a clinic for sexually transmitted diseases in San Francisco. None of 70 men with negative HTLV-III antibody tests had a positive virus culture; 43 (60%) of 72 with repeatedly reactive tests were culture-positive. Among these 72 antibody-positive blood samples, 70 (97%) were highly reactive and 97% of those tested to date had a positive Western blot test as well. Plasmapheresis facilities are generally notifying donors when a repeatedly reactive EIA test result is obtained. Blood banks at present are often seeking confirmation of EIA reactive results by Western blot before notifying donors. Fewer than 2% of reported AIDS cases have been thought to be transmitted by blood transfusion. Even this risk will be virtually eliminated with the application of the new test coupled with the continued use of self-exclusion criteria for high risk donors. In September 1985, these criteria were broadened to include not only members of high-risk groups, but also any man who has had sex with another man since 1977, including those who had only a single homosexual experience. This change was prompted by the discovery that the majority of individuals having confirmed positive HTLV-III test results have been homosexual or bisexual males who felt they were not in a risk group.4 Because the incubation period for AIDS can be more than five years, new cases of transfusion-associated AIDS can be expected to appear for some time in persons infected with HTLV-III before the blood screening test came into use. In addition to its use in screening donated blood, Public Health Service (PHS) has recommended that the EIA for HTLV-III antibody be used to screen blood and serum from donors of organs, tissue or semen intended for human use, and that the test result be used to evaluate the appropriate use of such materials from these donors." Data have established that hemophilia A patients treated with Factor VIII concentrates had a significantly greater risk of contracting AIDS than any other blood (or blood product) recipient group. Recent adoption of heat (or chemical) processes to inactivate viruses, including HTLV-III, by U.S. licensed manufacturers of Factor VIII, together with the screening of the blood supply, have now virtually eliminated this risk. Factor IX concentrate, used to treat hemophilia B, has only rarely been thought to transmit HTLV-III; however, a viral inactivation step is being added to its manufacturing process as well. FDA Letter In a letter mailed to physicians in March 1985, preceding the approval of the first EIA test kit, FDA emphasized that the screening kits do not constitute a diagnostic test for AIDS, but rather are useful to identify-through the presence of antibody-those who have been infected by HTLV-III and therefore might transmit the disease. As with any serologic test, there will be some falsepositive results even in repeatedly reactive samples. These apparently aberrant results may represent biologically falsepositive reactions such as cross reactivity to other antigens or nonspecific reactions. Positive antibody test results are more likely to be a true indication of HTLV-III infection when the prevalence of infection by the virus in the population being screened is higher. PHS Recommendations 7 PHS has issued recommendations for screening donated blood for HTLV-III antibody. Summarized, these include: Screening all plasma and blood for HTLV-III antibodies. • Blood or plasma that is reactive for HTLV-III antibody should not be transfused or used for manufacture into injectable products capable of transmitting infectious agents. Notifying the donor only upon a positive result from a second EIA or other test (e.g., Western blot) and referring the donor to a physician for evaluation. • Keeping positive test results confidential. Whenever possible, donor deferral lists should be general, without specifying the reason for inclusion on the list. Recommendations For Patients Physicians and other health practitioners whom patients consult after having been told they have repeatedly reactive test results can advise their patients of the following: 7 • The prognosis for an individual infected with HTLV-III over the long term |