Press Release

Persistent Lack of Detectable HIV-1 in a Person with HIV infection, Utah

CDC, in collaboration with the Utah Department of Health (UDH) and the Food and Drug Administration (FDA), has investigated the case of a Utah man diagnosed with AIDS who persistently tested negative for HIV-1 antibodies.

The body usually begins making antibodies within days of HIV infection. Usually enough antibodies are made within several weeks that are detected by an HIV antibody test. HIV antibody tests indicate the presence of HIV, but do not directly detect the virus. Additional tests by CDC and FDA for HIV antigen (the core protein in the virus itself) and for HIV genetic material have confirmed that the Utah man is infected with HIV.

After learning of his diagnosis, he reported that he had previously sold plasma to a commercial plasma center. The investigation, therefore, included assessing whether there was possible HIV transmission through the donated plasma.

Plasma Recipients Never Threatened

Current procedures to ensure the safety of the blood supply include donor selection (the process of deferring high-risk donors through oral and written questioning) and blood and plasma screening for HIV antibodies. Additionally, plasma is routinely treated either by heat or by a solvent detergent process during the manufacture of commercial plasma derivatives. Both processes have been shown to inactivate HIV.

Because HIV antibody testing by the plasma center did not detect antibodies in this man's plasma, his plasma was accepted. It is not known if any of this plasma was collected after he became infected. However, even if the man were infected at the time of donation, standard plasma processing procedures would have killed any HIV in his plasma. A thorough review of the center's records confirmed that the man's plasma was processed to inactivate HIV before any derived HIV-inactivated products were used. Therefore, the plasma products were free of HIV.

Atypical Immune Response Likely the Cause of Failure to Test Positive for HIV-Antibodies

It has not yet been determined why this individual's antibody tests were negative, but the investigation has revealed that it is most likely due to a rare immune reaction by the patient. It is well recognized that there is a "window period" from the time of HIV infection until the time the immune system has produced enough antibodies to the virus to be detected by antibody tests. This period is usually several weeks. After this initial window period, it is rare for a person to continue to test negative for HIV antibodies. This individual was clearly not in the window period; clinical symptoms of advanced HIV disease had already developed.

CDC is aware of other isolated reports in which an HIV-infected person who has passed the window period did not produce enough antibodies to be detected. The immune system of an infected person typically produces an amount of HIV antibody much greater than the amount of HIV antigen (core protein) in the person's blood. The antibodies bond with the HIV antigen, and only excess, unbound antibodies can be detected. In extraordinarily rare cases, if an individual's immune system for some reason does not make excess antibodies, the standard enzyme immunoassay (EIA) test for HIV antibodies would not detect unbound antibodies.

In addition, there have been reports of individuals outside the United States who, after being infected with a geographically isolated strain of HIV, produced antibodies that were not detectable on all the tests commercially available in the U.S. However, the genetic analysis found that this man was infected with subtype B, the strain commonly found in the U.S. The analysis also confirmed that he was infected by his wife, who was diagnosed with AIDS in 1994. His wife consistently tests positive for HIV antibodies, indicating that the man's failure to test positive is related to his immune response to the virus, rather than to the virus itself. This atypical immune response is thought to be extremely rare. Physicians who treat patients with clinical signs of AIDS but a negative antibody test should discuss additional testing with their state health department laboratory.

Recent Recommendations to Further Protect the Blood Supply

The results of the investigation also suggest that recent FDA recommendations for p24 antigen screening could have additional benefits. While this man failed to test positive for antibodies, he did test positive for HIV antigen. Unusual cases such as his would be detected by the additional screening test for p24 antigen that the FDA is expected to license for doonor screening nationwide. This antigen test can detect the virus about a week before antibodies to the virus can be detected. This recommendation was issued primarily because it shortens the window period between infection and the ability to detect infection, but antigen testing may also identify those rare HIV-infected donors without detectable antibodies to HIV.

The p24 antigen test will reduce the extremely low risk of HIV transmission through blood transfusions even further. The Public Health Service has already issued recommendations for blood banks to use in interpreting test results and counseling donors with positive or indeterminate results (MMWR Reports and Recommendations, March 4, 1996, "Testing and Counseling Blood and Plasma Donors for Human Immunodeficiency Virus Type 1 Antigen: Guidelines of the U.S. Public Health Service").

CDC does not recommend the p24 antigen test for routine use in HIV counseling and testing sites. Guidelines for counseling and testing individual patients already take into account the window period and recommend follow-up antibody testing. Antigen testing detects HIV infection only a few days before antibody testing does. And the time in which the antigen can be found is very short -- once antibodies are detectable, antigen is often not detectable. Antibody testing at the recommended intervals is the best way for health care providers to routinely diagnose HIV in individual patients.

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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES