HIV is short for human immunodeficiency virus. This is the virus that causes the acquired immunodeficiency syndrome or AIDS. HIV is a complicated virus. It reproduces primarily in specialized cells of the body’s immune system called CD4 lymphocytes. During HIV replication, the CD4 cells are destroyed. As more and more cells are killed, the body loses the ability to fight many infections. If the number of CD4 cells in the bloodstream falls below 200 per cubic millimeter, or if some other special health conditions occur, the person is defined as having AIDS. These special health conditions include infections and cancers that take advantage of the suppressed immune system. Regardless of the CD4 count, people with HIV infection carry the virus and can spread it to others through unprotected sex or contact with blood or some other body fluids.
People who are at high risk for acquiring HIV should be tested at least annually. Sometimes, health care professionals request or require testing as part of evaluation and treatment for other conditions, such as women undergoing treatment with assisted reproductive technologies for infertility or treatment of viral hepatitis. There is increasing concern that not enough people are being tested. Events such as National Or World AIDS AWARENESS Day have been used to raise awareness and increase participation in testing.
In some cases, HIV testing may be required by law. This occurs for blood that is used for transfusions, organ donors, and military personnel. States may select additional populations for mandatory testing, such as prisoners or newborns.
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There are three main types of HIV tests: antibody tests, RNA (viral load) tests, and a combination test that detects both antibodies and viral protein called p24 (antibody-antigen test, or HIV Ab-Ag test). All tests are designed to detect HIV-1, which is the type of HIV in the United States. Some antibody tests and the combination test can also detect HIV-2 infections, which are usually limited to West Africa. No test is perfect; tests may be falsely positive or falsely negative or impossible to interpret.
HIV antibody tests (ELISA/CLIA): HIV possesses many unique proteins on its surface and inside the virus itself. When someone is infected with HIV, their body produces proteins designed to tag the virus for elimination by the immune system. These proteins are called antibodies, and they are directed against the unique proteins of HIV. Unfortunately, these HIV antibodies do not eliminate the virus, but their presence serves as a marker to show that someone is infected with HIV. HIV antibody tests are the most commonly used tests to determine if someone has HIV.
Antibody testing is usually done on a blood sample, often using an enzyme-linked assay called an ELISA or CLIA. In this test, a person’s serum is allowed to react with virus proteins that have been produced in the laboratory. If the person has been infected with HIV, the antibodies in the serum will bind to the HIV proteins, and the extent of this binding can be measured. Negative CLIA results are usually available in a day or so.
RAPID TEST: There are some rapid HIV testing kits on the market that can be used in a health care professional’s office or other points of care. Most of these kits still require blood to be drawn, although it can be done using a simple finger stick in some cases.
HIV RNA tests: The HIV RNA is different than all human RNA, and tests have been developed to detect HIV RNA in a person’s blood. Because this test can be used to estimate the amount of circulating HIV in the blood, it is often referred to as an HIV viral load. This uses a type of test called a polymerase chain reaction (PCR). These tests are important for newborn screening of HIV-positive mothers since maternal antibody may cross the placenta and be present in the newborn. These tests may also be helpful in detecting HIV infection in the first four weeks following exposure, before antibodies have had time to develop. However, they are costly and are not routinely used to screen for infection.
HIV antibody-antigen (Ab-Ag) test: The HIV Ab-Ag test detects antibodies directed against HIV-1 or HIV-2, as well as a protein called p24, which forms part of the core of the virus (an antigen of the virus). This is important because it takes weeks for antibodies to form after the initial infection, even though the virus (and the p24 protein) is present in the blood. Thus, Ab-Ag testing may allow for earlier detection of HIV infections. Preliminary studies suggest that diagnosis could be made an average of one week earlier using the Ab-Ag test, compared to antibody testing alone. The test uses a reaction known as “chemiluminescence” to detect antibodies and p24 protein antigen. In other words, if either the antibody or the antigen is present, the test reaction emits light that registers on a detector. There is only one currently approved antibody-antigen test, the Architect HIV Ag/Ab Combo assay. If this test is positive, it is recommended it be repeated. Tests that remain positive are confirmed with Western blot as described above.
The current testing protocols are highly accurate but not perfect. The probability of a false result on the test depends on the test and on the person’s risk factors for getting infected. The lower the risk of getting HIV, the higher the probability of a false- positive result.
Falsely negative tests occur in people who are truly infected with HIV but have negative tests. Among 1,000 people who are truly infected, rapid tests will be falsely negative in zero to six people, depending on the test. Negative antibody tests in people infected with HIV may occur because antibody concentrations are low or because antibodies have not yet developed. On average, antibodies take about four weeks to reach detectable levels after initial infection, and falsely negative tests may occur during this so-called HIV window period. Individuals with negative tests and who had high risk for HIV exposure should be retested in two to three months.
Falsely positive tests occur when uninfected people have positive results. Among 1,000 people who do not have disease, rapid tests will be falsely positive in zero to nine people, depending on the test. This is the main reason for not relying on a single positive test for diagnosis. As discussed above, all positive initial tests must be confirmed with a follow-up test (Western blot). When both tests are positive, the likelihood of a person being HIV infected is >99%. Sometimes, the Western blot may be indeterminate, meaning that it is neither positive nor negative. In these cases, the tests are usually repeated at a later date or an RNA test is done.
HIV testing is critically important for pregnant women. HIV testing is recommended at the beginning of each pregnancy during prenatal care. If any HIV risk factors are present or there is a high incidence of HIV in the population, testing should be repeated in the third trimester. There have been enormous advances in the treatment of HIV-infected pregnant women. With proper management, the probability of transmitting the virus to the fetus is less than 2%. Without proper management, the risk of transmission is as high as 33%. Because undiagnosed HIV is so common, it is necessary to test all pregnant women. It is strongly recommended that all children born to women with HIV also be tested.
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