What is a Cluster of Differentiation 4 test?

A cluster of differentiation 4 (CD4) test is used to determine the number of CD4+ cells in body. CD4+ cells are one of the many cells that are a part of the immune system. Immunity is divided into two types:

  • Innate immunity: It is the immunity that an individual is born with.
  • Adaptive immunity: It develops after exposure to certain disease-causing agents called antigens

 The cells that carry out adaptive immunity are of two types:

  • T lymphocyte cells, which are generated in the thymus gland located in the neck region
  • B lymphocyte cells, which are generated in the bone marrow.

CD4+ cells are a type of T lymphocytes, which help in the formation of other T lymphocytes and help B cells to produce antibodies.

The human immunodeficiency virus (HIV) is a type of antigen that attacks CD4+ cells specifically by binding to its surface and then fusing with the human CD4+ cells. It then multiplies rapidly and affects many more CD4 T lymphocytes, leading to a transient drop in CD4+ levels in blood within 2-3 weeks post initial infection. As this disease progresses, the rate of production of new CD4+ cells cannot keep up with its destruction rate, leading to a drastic decrease in its circulating levels. Low levels of these cells lead to a harmful effect on immunity and give way to opportunistic infections.

  1. Why is CD4 count test performed?
  2. How do you prepare for a CD4 count test?
  3. How is a CD4 count test performed?
  4. CD4 count test results and normal range

A CD4 test is performed after the detection of HIV in blood. As a decreasing number of CD4+ cells is a sign of disease progression, it is an important test to classify the patient into different stages of immunodeficiency.

A CD4 test is also required as an objective tool to help decide the initiation and choice of antiretroviral therapy (ART). The responsiveness to ART is also assessed based on the changes in CD4+ cell count.

Along with CD4 test,  plasma viral load test is also a sensitive indicator of the progression of  HIV infection. However, since it is a more expensive test to perform, CD4 test remains the test of choice to measure disease progression.

A CD4 test may also be performed after organ transplants to detect whether the body has accepted the donor organ successfully or not.

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CD4 test does not require any special preparations.

A small quantity of blood is withdrawn from a vein in the arm by inserting a needle. The sample is collected into a syringe and stored in a container. Only a small quantity of blood is required for this test. The individual will feel a momentary pain on needle insertion but the test itself is risk-free. Sampling process does not usually take more than five minutes.

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Normal results: The normal range of CD4+ cells is 410-1590 cells per cubic millimetre (/mm3). If test results are within this range, it indicates that the ART is effective. However, results must only be interpreted in terms of the clinical question at hand. This test must not be used as a substitute for HIV test, as many acute viral and bacterial infections, as well as other medical problems, can also lead to a reduction in CD4+ cell count.

Abnormal results: A cell count range between 250 and 500 cells/mm3 signifies a weakened immune system, and the individual may be prone to serious bacterial infections, such as pneumonia; meningitis; pulmonary tuberculosis (TB); and fungal infections, such as oral candidiasis. He/she may have other unexplained symptoms, such as persistent diarrhoea, for more than one month, with drastic weight loss of greater than 10% of body weight, persistent fever and anaemia.

If the CD4 test shows a range below 200 cells per cubic millimetre, it is indicative that the HIV has led to full-blown acquired immunodeficiency syndrome (AIDS). The symptoms of AIDS include:

  • HIV wasting syndrome
  • Recurrent severe bacterial pneumonia
  • Chronic herpes simplex infection around the genitalia, which persists for more than one month
  • Oesophageal candidiasis or candidiasis of the trachea, bronchi or lungs
  • Extra-pulmonary TB, ie tuberculosis not restricted to the lungs and affecting other organs such as the spine
  • Kaposi sarcoma, a disease in which malignant skin tumours originate from blood vessels
  • Toxoplasmosis of the central nervous system
  • HIV encephalopathy
  • Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

Low values of CD4+ cells must also be clinically correlated to begin ART. Initiation of ART is recommended when CD4+ levels are below 350 cells/mm3, and the individual is suffering from pulmonary TB or any other serious bacterial infection.

Benefits of ART outweigh the risk to a pregnant woman and the foetus when the CD4+ count is less than 350 cells/mm3, and the woman has contracted any of the severe conditions mentioned above.

Disclaimer: All results must be clinically correlated with the patient’s complaints to make a complete and accurate diagnosis. The above information is provided from a purely educational perspective and is in no way a substitute for medical advice from a qualified doctor.


  1. US Department of Veteran Affairs; CD4 count (or T-cell count). [Updated Feb 8 2018]
  2. Jameson JL, Kasper DL, Fauci AS, Longo DL, Hauser SL, Loscalzo J. Harrison’s Principles of Internal Medicine. 20th ed. USA: McGraw Hill education; 2018. Chapter 342, Introduction to the immune system pp 2451-2479.
  3. World Health Organization [Internet]. Geneva (SUI): World Health Organization; Laboratory Guidelines for enumerating CD4 T Lymphocytes in the context of HIV/AIDS
  4. Provan D. Oxford handbook of clinical and laboratory investigation. 4th ed. Oxford, UK: Oxford university press; 2018. Chapter 4, Immunology and allergy pp 334-380
  5. National Institute of Health. AIDS info [internet]: Bethesda (MA), US. US Department of Health and Human Services CD4 Count
  6. Nathan Ford, Graeme Meintjes, Marco Vitoria, Greg Greene, and Tom Chiller. The evolving role of CD4 cell counts in HIV care. 1746-630X Copyright 2017 Wolters Kluwer Health, Inc.

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