CD4 count and percentage

Basics

Leukocytes are identified using their Cluster of Differentiation (CD), which is a type of molecule (glycoprotein) that mostly act as receptors. For instance, Helper T cells (CD3+ and CD4+), Cytotoxic T cells (CD3+ and CD8+), Natural Killer Cells (CD16+ and CD56+), B cells (CD3- CD19+), Monocytes (CD3- and CD14+) and so on. All leukocyte groups include the CD45+ group. Other cells such as Thrombocytes (CD45+ and CD61+) as well as stem cells may also have these groups.

Hence, if we request for “CD4 cell count”, we will be requested to identify the number of Helper T cells. We are also aware that HIV mainly affects (apart from other cells) these CD4 Helper T-cells, and hence we may expect them to be lower in number. If we request “CD45+ count”, we are essentially requesting the cell count for all the cells containing such cluster.

The Laboratory

The laboratory measures these cell groups by using FLOW CYTOMETRY. It may take around 20 hours depending on the laboratory to get the results. The results will be written as an Absolute CD4 count, CD4% of lymphocytes, and CD45+ white cell count. The laboratory OBTAINS/CALCULATES the absolute CD4 count by multiplying the percentage with the total measured white blood cell count. The normal CD4 count is around 500 – 1500 cells/uL. The normal range for the CD4 percentage is around 30% to 60%.

The CD4 percentage usually correlates with a particular CD4 count. For instance:

  1. CD4 percentage > 29% = CD4 Count > 500 cells/uL
  2. CD4 percentage 14 to 28% = CD4 Count 200 to 499 cells/uL
  3. CD4 percentage <14% = CD4 Count < 200 cells/uL

NB: CD4 count depends on (1) percentage and (2) total white blood cell count (WBC). The CD4 percentage has less variation and it is more likely to remain the same, but changes in WBC may affect the reading of the CD4 count.

Importance

The CD4 count and CD4 percentage can be used in order to assess and monitor the patient’s IMMUNOLOGICAL status. It is also important for the initiation of prophylactic treatment and performance of special investigations especially if the CD4 count is < 200 cell/uL.

Factors affecting CD4 reading

  1. Normal individual variation, day-night variations in CD4 count may occur. It is more important to assess the TREND of CD4 count rather than using an absolute value.
  2. Any factor changing the value of the WBC may also affect the CD4 count. In general, leukocytosis may increase the CD4 count while a leukopenia may decrease the CD4 count. This is because the CD4 percentage remains relatively unchanged, and then the WBC is used to measure the CD4 count.
    1. Infections
      1. Decreased CD4: EBV, CMV, HTLV-1, Tuberculosis
    2. Medications
      1. Corticosteroids affects the WBC
    3. Chronic conditions
      1. Splenectomy: Increased in CD4 count
      2. Liver disease, Splenomegaly: These conditions may be related to splenic sequestration and will result in lower CD4 counts.
      3. Alcohol use disorder: Decreased CD4 count

It is important to be aware, that for children younger than 5 years of age, doctors prefer to use CD4 percentages for monitoring disease progression rather than CD4 count because there is an normal age-related changes in absolute CD4 counts. Hence, if you use CD4 counts, you may struggle to assess the TREND of CD4 changes appropriately.

NB: Once the CD4 count and the CD4 percentage are not correlating, the doctor should try identifying the reason why this has occurred. This can be done by reviewing the “factors affecting CD4 reading”.

Monitoring

It is important to understand that during viral suppression, the CD4 count will rise slowly. It is suggested from an article on NCBI (like under further reading), that one may expect the CD4 count to rise by 50 cells/uL AFTER 4 – 8 weeks while on treatment, then approximately 100 – 150 cells/uL from baseline to a year. This is then followed by a yearly increment of 50-150 cells/year. The rate at which one improves their CD4 count will depend on the age of the patient, the degree of immunosuppression, and how low the CD4 count was at baseline. This may explain why the guidelines may suggest checking CD4 counts at 3-6 month intervals or even yearly.

NB: Do not use CD4 count to assess virological failure or adherence to the patient’s treatment. There are other parameters used for such, and there are also other factors that affect the CD4 count which may not relate to either.

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