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Most often, this test is done to measure the strength of your immune system if you have been diagnosed with human immunodeficiency virus (HIV) infection and to monitor the effectiveness of treatment; occasionally, it may be used with other conditions (see Common Questions below).
When you are first diagnosed with HIV infection to get a baseline assessment of your immune system; about every 3 to 6 months after starting antiretroviral therapy (ART) to check whether you are responding to treatment; if you have responded well to treatment, you may then be tested every 6 to 12 months.
A blood sample drawn from a vein in your arm
CD4 cells are white blood cells called T lymphocytes or T cells that fight infection and play an important role in immune system function. CD4 tests measure the number of these cells in the blood and, in conjunction with an HIV viral load test, help assess disease status in a person who has been diagnosed with human immunodeficiency virus (HIV) infection.
CD4 cells are made in the thymus gland and they circulate throughout the body in the blood and lymphatic system. They are so called because they have markers on their surfaces called clusters of differentiation (CD). The CD number identifies the specific type of cell.
CD4 cells are sometimes called T-helper cells. They help to identify, attack, and destroy specific bacteria, fungi, and viruses that cause infections. CD4 cells are also a major target for HIV, which binds to the surface of CD4 cells, enters them, and either replicates immediately, killing the cells in the process, or remains in a resting state, replicating later.
If HIV goes untreated, the virus gets into the cells and replicates, the viral load increases, and the number of CD4 cells in the blood gradually declines. The CD4 count decreases as the disease progresses. If left untreated, this process may continue for several years until the number of CD4 cells drops to a low enough level that symptoms associated with AIDS begin to appear.
Treatment for HIV infection, called antiretroviral treatment (ART or ARV) or sometimes highly active antiretroviral therapy (HAART), typically involves taking a combination of drugs. This treatment reduces the amount of HIV (viral load) present in the body and reduces the risk of disease progression. When this occurs, the CD4 count will increase and/or stabilize.
CD4 counts can be variable, even in healthy individuals. To provide a clearer picture of the condition of the immune system, test results may also be reported as a CD4 percentage, which is the ratio of CD4 cells to total lymphocytes.
CD4 tests may be used occasionally in other conditions, such as lymphomas and organ transplantation (see Common Questions below).
CD4 counts, along with an HIV viral load, are most often used if you are diagnosed with HIV infection to:
It is recommended that all individuals diagnosed with HIV infection receive antiretroviral treatment as soon as possible, including pregnant women, to reduce the risk of disease progression. People typically take at least three drugs from two different classes in order to prevent or minimize virus replication and the emergence of drug-resistant strains. Combinations of three or more antiretroviral drugs are referred to as highly active antiretroviral therapy or HAART.
CD4 counts are most useful when they are compared with results obtained from earlier tests. Since CD4 cells are usually destroyed more rapidly than other types of lymphocytes and because absolute counts can vary from day to day, it is sometimes useful to look at the number of CD4 cells compared to the total lymphocyte count. The result is expressed as a percentage, i.e., CD4 percent.
Sometimes, CD4 tests may be used to help diagnose or monitor other conditions such as lymphoma, organ transplantation, and DiGeorge syndrome (see below).
A CD4 count is usually ordered along with an HIV viral load when you are first diagnosed with HIV infection as part of a baseline measurement. After the baseline, a CD4 count will usually be ordered at intervals over time, depending on a few different factors.
The following table summarizes recommendations* for the timing of CD4 counts and viral load testing:
|Clinical Status of Patient||Viral Load||CD4 Count|
|When first diagnosed||Test performed||Test performed|
|If ART is delayed||Optional||Every 3-6 months|
|After initiating ART||Within 2-4 weeks and then every 4-8 weeks until virus is suppressed (undetectable)||3 months later|
|During the first 2 years of stable ART||Every 3-4 months||Every 3-6 months|
|Virally suppressed on ART for greater than 2 years||Can extend to every 6 months||Annually; if CD4 consistently greater than 500 cells/mm3, monitoring is optional|
|While on ART and viral load is consistently greater than 200 copies/mL||Every 3 months||Every 3-6 months|
|With new HIV symptoms or start of new treatment with interferon, corticosteroids or cancer drugs||Every 3 months||Perform test and monitor according to health status (e.g., new HIV symptoms, opportunistic infections)|
*Adapted from Guidelines for the Use of Antiretroviral Agents in HIV-1–Infected Adults and Adolescents, Table 4. Recommendations on the Indications and Frequency of Viral Load and CD4 Count Monitoring.
A CD4 count is typically reported as a count of cells (expressed as cells per cubic millimeter of blood). Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).
Once the virus has been suppressed due to ART, CD4 counts typically rise and/or stabilize over time, indicating that you are responding to treatment. Within the first year of treatment it is normal for the CD4 count to increase by 50-150 cells/mm3. However, a slower change in the CD4 count is typically not sufficient to change treatment. It is rare for the CD4 count to decline when the virus is suppressed due to ART.
Importantly, any single CD4 test result may differ from the last one even though your health status has not changed. Usually, a healthcare practitioner will take several CD4 test results into account rather than a single value and will evaluate the pattern of CD4 results over time.
The CD4 count tends to be lower in the morning and higher in the evening. Acute illnesses, such as pneumonia, influenza, or herpes simplex virus infection, can cause the CD4 count to decline temporarily. Cancer chemotherapy can dramatically lower the CD4 count.
The CD4 count does not always reflect how someone with HIV disease feels and functions. For example, some people with higher counts are ill and have frequent complications, and some people with lower CD4 counts have few medical complications and function well.
HIV infection is usually screened for with a test for HIV antibody and antigen (p24). If the screening test is positive, it must be followed with another test, such as a second antibody test that can differentiate HIV-1 and HIV-2. If results of the first and second test do not agree, then an HIV-1 RNA test (nucleic acid amplification test, NAAT) is performed. If either the second antibody test or the HIV-1 RNA is positive, then you are diagnosed with HIV infection. Read the article on HIV Antibody and HIV Antigen (p24) for more details.
Opportunistic infections are those that occur more frequently in people who have a weakened immune system. For people infected with HIV, a CD4 count less than 200 cells/mm3 puts you at risk for opportunistic infections, including pneumocystis pneumonia, toxoplasma encephalitis, cytomegalovirus (CMV) retinitis, tuberculosis and disseminated infections caused by nontuberculosis mycobacteria, cryptococcal meningitis, as well as candidiasis and other fungal infections. The Centers for Disease Control and Prevention (CDC) provides a table with examples of common opportunistic infections. Viral suppression virtually eliminates this risk.
In general, treatment is recommended regardless of whether the CD4 count is low or within the normal range. You and your healthcare provider should discuss your treatment options to determine what will work best for you. The Mayo Clinic web page HIV/AIDS: Treatments and drugs has detailed information on various therapies.
Yes. It may be ordered when a person has had an organ transplant to help evaluate the effect of immunosuppressive medications. In transplantation, the immune system must be suppressed so that it does not attack the transplanted organ and cause rejection. In this case, it is desirable to have low levels of CD4 cells, and a decreased count shows that the drug is working. A CD4 count may be repeated periodically to monitor the effectiveness of therapy.
CD4 counts are sometimes done in conjunction with CD8 counts. CD8 cells are another type of lymphocyte called T-suppressor cell or cytotoxic T cell. CD8 cells identify and kill cells that have been infected with viruses or that have been affected by cancer.
Evaluation of CD4 and CD8 cells may be used to help classify lymphomas. Typically, several markers on the surface of lymphocytes in addition to CD4 and CD8 are evaluated. The tests help determine whether the lymphoma is due to the proliferation of B lymphocytes or T lymphocytes and which specific type. This information is useful in determining appropriate therapy.
These tests may also help diagnose DiGeorge syndrome, a rare congenital disorder characterized by, among other things, low levels of T cells in the blood. For more information on DiGeorge syndrome, visit the Mayo Clinic web site.
Sources Used in Current Review
2019 Review completed by Jenna Rychert, PhD, D(ABMM), Medical Director, ARUP Laboratory.
IDSA Guideline: Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Available online at https://www.idsociety.org/globalassets/idsa/practice-guidelines/primary-care-guidelines-for-the-management-of-persons-infected-with-hiv-2013-update-by-the-hiv-medicine-association-of-the-infectious-diseases-society-of-america.pdf. Accessed April 10, 2019.
NEW YORK STATE DEPARTMENT OF HEALTH AIDS INSTITUTE Guideline: Virologic and Immunologic Monitoring. June 2016. Available online at https://www.hivguidelines.org/antiretroviral-therapy/cd4-and-viral-load-monitoring/#tab_0 Accessed. April 10, 2019.
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