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.
NIH AIDSinfo Guideline: Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. March 2019. Available online at https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed April 10, 2019.
NIH AIDSinfo Guideline: Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. October 2018. Available online at https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed April 10, 2019.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Janice K. Pinson MT, MBA. Molecular Business Strategies, Birmingham, MI.
Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 535-538.
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp 487-490.
Bennett, N. and Rose, F. (2008 October 22, Updated). HIV Disease. eMedicine [On-line information]. Available online at http://www.emedicine.com/med/TOPIC24.HTM. Accessed on 10/26/08.
Mayo Clinic Staff (2008 August 9). MayoClinic HIV/AIDS. MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/hiv-aids/DS00005. Accessed on 10/30/08.
(2005 November, Revised). Human Immunodeficiency Virus (HIV) Introduction. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec14/ch192/ch192a.html?qt=HIV&alt=sh. Accessed on 10/30/08.
(2008 September, Reviewed). Human Immunodeficiency Virus – HIV. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/InfectiousDz/Viruses/HIV.html. Accessed on 10/30/08.
(2006 September 22). Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings. CDC MMWR 55(RR14);1-17 [On-line information]. Available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm. Accessed on 11/1/08.
(2008 September 26). CD4 Monitoring of HIV Patients a Cost-Saving Strategy in Poor Countries. Medscape from Reuters Health Information [On-line information]. Available online at http://www.medscape.com/viewarticle/581174. Accessed on 10/26/08.
Moing, V. et. al. (2007 May 22). From HIV Medicine Long-term Evolution of CD4 Count in Patients With a Plasma HIV RNA Persistently <500 copies/mL During Treatment With Antiretroviral Drugs. Medscape from HIV Medicine [On-line information]. Available online at http://www.medscape.com/viewarticle/556494. Accessed on 11/1/08.
Moore, D.M. et. al. (2006 September 13). CD4 Percentage is an Independent Predictor of Survival in Patients Starting Antiretroviral Therapy with Absolute CD4 Cell Counts Between 200 and 350 Cells/UL. Medscape from HIV Medicine [On-line information]. Available online at http://www.medscape.com/viewarticle/543496. Accessed on 11/1/08.
Baker, J. et. al. (2008 July 18). CD4+ Count and Risk of Non-AIDS Diseases Following Initial Treatment for HIV Infection. Medscape from AIDS 2008;22(7): 841-848. [On-line information]. Available online at http://www.medscape.com/viewarticle/575829. Accessed on 11/1/08.
Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007. Pp 317, 600-604, 820 and 1923.
(Updated November 13, 2008) National Institute of Allergy and Infectious Diseases. Understanding How HIV Causes AIDS. Available online at http://www3.niaid.nih.gov/topics/HIVAIDS/Understanding/howhiv.htm. Accessed February 2008.
LabCorp CD4:CD8 Ratio Profile. Available online through https://www.labcorp.com. Accessed February 2009.
ARUP Consult. Leukemia and Lymphoma Phenotyping. Available online at http://www.arupconsult.com/Topics/OncologicDz/Lymphomas/LeukemiaLymphomaPhenotyping.html#. Accessed March 2009.
(August 9, 2007) MayoClinic.com. DiGeorge Syndrome. Available online at http://www.mayoclinic.com/health/digeorge-syndrome/DS00998. Accessed March 2009.
Anand, J. (Updated 2011 August 11). Antiretroviral Therapy in Treatment-Naive Patients. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/2041458-overview. Accessed February 2012.
Hughes, R. et. al. (2011 November 21). Long-term Trends in CD4 Cell Counts and Impact of Viral Failure in Individuals Starting Antiretroviral Therapy. Medscape Today from HIV Medicine v12 (10):583-593 [On-line information]. Available online at http://www.medscape.com/viewarticle/753337. Accessed February 2012.
Bennett, N.J. and Gilroy, S. (Updated 2011 November 9) HIV Disease. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/211316-overview. Accessed February 2012.
Bennett, N. (Updated 2011 July 14). Laboratory Assays in HIV Infection. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1995114-overview#showall. Accessed February 2012.
Dugdale, D. (Updated 2011 June 9). AIDS. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000594.htm. Accessed February 2012.
(© 1995–2012). Test ID: TCD4 CD4 Count for Immune Monitoring, Blood. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/84348. Accessed February 2012.
Hillyard, D. et. al. (Updated 2011 November). Human Immunodeficiency Virus - HIV. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/HIV.html?client_ID=LTD. Accessed February 2012.
(Revised 2011 March 10). CD4 (T-cell) Tests. AIDS InfoNet [On-line information]. Available online at http://aidsinfonet.org/fact_sheets/view/124. Accessed February 2012.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 244-247.
Clarke, W., Editor (© 2011). Contemporary Practice in Clinical Chemistry 2nd Edition: AACC Press, Washington, DC. Pp 609-612.
(2015 April 8, Updated). Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available online at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed May 17, 2015.
(2014 September 23, Revised). CD4 Count. AIDS.gov [On-line information]. Available online at https://www.aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/understand-your-test-results/cd4-count/. Accessed May 17, 2015.
Bennett, N. (2014 December 17, Updated). Laboratory Assays in HIV Infection. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/1995114-overview#showall. Accessed May 17, 2015
Bennett, N. and Gilroy, S. (2015 January 23, Updated). HIV Disease. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/211316-overview#showall. Accessed May 17, 2015.
Ford, N. et. al. (2015 February). The future role of CD4 cell count for monitoring antiretroviral therapy. Lancet Infect Dis 2015; 15: 241–47. [On-line information]. Available online at http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(14)70896-5.pdf. Accessed May 17, 2015.
Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report (MMWR). Revised Surveillance Case Definition for HIV Infection — United States, 2014. Recommendations and Reports, April 11, 2014 / 63(RR03);1-10. Available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6303a1.htm?s_cid=rr6303a1_e. Accessed June 2015.