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,3 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

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
With Reactive Tests

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

is not known. However, data suggest that most persons will remain infected for life.

• Even though asymptomatic, persons with repeatedly reactive HTLV-III antibody tests may transmit infection to

others through sexual intercourse, sharing of needles and, possibly, exposure of others to saliva through oral-genital contact or intimate kissing. Recent research has revealed that HTLV-III is also present in the tears of AIDS patients but there is no evidence of transmission through tears. The efficacy of condoms in preventing infection with HTLV-III is unproven, but the consistent use of them may reduce transmission. Toothbrushes, razors, or other implements that could become contaminated with blood should not be shared. • Regular medical evaluation and follow up is advised, especially for patients who develop signs and symptoms suggestive of AIDS.

• Persons with repeatedly reactive HTLV-III antibody tests should not donate blood, plasma, body organs, other tissue or sperm.

• Women with repeatedly reactive antibody tests or whose partners are seropositive, are at increased risk of acquiring AIDS. If they become pregnant their offspring are also at increased risk. • If persons with repeatedly reactive antibody tests have accidents involving bleeding, contaminated surfaces should be cleaned with household bleach freshly diluted 1:10 in water.

When seeking medical, dental or eye care, these persons should advise the practitioner of their positive antibody status so that appropriate evaluation can be undertaken and precautions can be taken to prevent transmission to others.

Devices used on these patients that have punctured the skin (such as hypodermic and acupuncture needles) should be steam-sterilized by autoclave before reuse or safely discarded. Whenever possible, disposable needles and equipment should be used.

• Testing for HTLV-III antibody should be offered to persons who may have had intimate contact with seropositive individuals (e.g., sexual partners, persons with whom needles have

been shared, infants born to seropositive mothers).

Patients and their families can also be advised there is no evidence that HTLVIII is transmissible by casual contact including: living in the same house as an infected person; caring for an AIDS patient; eating food handled by an infected person; being coughed or sneezed upon by an infected person; casual kissing; or swimming in a pool with an infected person.

As with most other infectious diseases, the spectrum of responses to HTLV-III infection is varied. Because it represents the end of the spectrum, AIDS is the most easily recognized of these responses. But as with other viruses (e.g., poliomyelitis), infection with HTLV-III probably does not inevitably result in the worst outcome. Preliminary estimates by CDC suggest that fewer than approximately 10% of those infected have thus far developed AIDS; approximately 25% have had only relatively minor problems such as chronic lymphadenopathy. About twothirds of infected persons have remained asymptomatic, at least in the short term.

Precautions For

Health Care Practitioners

PHS previously recommended procedures for lab personnel, dentists and morticians' having contact with AIDS patients.

Recently, after NIH scientists isolated HTLV-III virus in tears, NIH, CDC and FDA issued recommendations in the Morbidity and Mortality Weekly Report of Aug. 30, 1985 (34:533-534). Summarized, they are:

• Health care professionals performing eye examinations or other procedures involving contact with tears should wash their hands immediately after a procedure and between patients. When practical and convenient, disposable gloves should be worn. The use of gloves is advisable when there are cuts, scratches or dermatologic lesions on the practitioner's hands.

Instruments that come into direct contact with external eye surfaces should be wiped clean and then disinfected by: