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Persistent Lack of Detectable HIV-1 in a Person with HIV infection, Utah, 1995
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
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.
** The full Morbidity and Mortality Weekly Report (MMWR) is available over the Internet. CDC's home page can be accessed at http://www.cdc.gov/. Select Publications, Products and Subscription Services to find the MMWR.
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