Why CD4 counts are measured

The CD4 cell count is the best known, most studied and readily available prognostic marker. It makes sense as a marker because decline in CD4 cell numbers is an effect of HIV, and CD4 T-cell depletion causes immune deficiency.

The CD4 cell count is a marker of likely disease progression, independent of viral load. Initially in HIV infection there is a sharp drop in the CD4 cell count and then usually stabilisation around 500 to 600 cells/mm³. Both the extent of the early drop in the count and the level at stabilisation are prognostic markers for the future risk of developing disease.

The best CD4 count to use to give an accurate prediction for the future is the most recent count. Irregular counts (those unexpectedly high and low) may be laboratory errors or real temporary or sustained changes which should be checked by repeating the count.

It is estimated that for every fall of 100 cells/mm³ in the CD4 cell count, the relative risk of developing AIDS is increased twofold. The absolute risk of developing AIDS, or not surviving, after having a particular count is changing over time as a result of treatment advances and other factors. The Swiss Cohort Study found that the average CD4 cell count fell by 46 cells/mm³ per half-year, and that the higher a person's CD4 cell count, the greater the CD4 cell count decline over a six-month period.¹ The CD4 cell count appears to decline more rapidly in the year before an AIDS diagnosis.

CD4 cell counts can also be used to predict the risks for particular AIDS conditions such as Pneumocystis pneumonia (PCP), cytomegalovirus (CMV) or Mycobacterium avium intracellulare (MAI). This can be extremely useful in deciding who will benefit from prophylactic (preventive) therapy, if it exists. For instance PCP prophylaxis is strongly recommended after the CD4 cell count has fallen below 200 cells/mm³, and MAI prophylaxis is recommended more often when the CD4 cell count is below 100 cells/mm³. Another example is the advice that HIV-infected people with CD4 cell counts below 200 cells/mm³ should boil water supplies to prevent cryptosporidial diarrhoea.

Sometimes doctors will assess the proportion of all lymphocytes that are CD4 cells. This is called the CD4 percentage. In HIV-negative people, a normal result is 40%. Among HIV-positive people the CD4 percentage tends to decline as HIV disease progresses. A CD4 percentage below 20% is thought to represent a risk of opportunistic infections equivalent to an absolute CD4 count of about 200 cells/mm³.

CD4 percentage is not very sensitive to small changes, but can be particularly useful if there is an unexpected CD4 result, for example a sudden drop. If the immune system is being damaged by HIV, one could expect the percentage of all lymphocytes to have decreased. However, if the percentage stays the same, it is more likely that the immune system was dealing with an infection, causing the CD4 count to drop.

Data from the SMART (Strategies for Management of Anti-Retroviral Therapy) study found that HIV-positive individuals with CD4 counts >350 cells/mm³ and with stable undetectable viral loads are at very low risk of disease progression and do not require frequent CD4 monitoring.² 

There are few data to guide decisions on the frequency of CD4 count monitoring in patients with undetectable viral loads (<50 copies/ml). Current US guidelines suggest checking every three to six months. There is no firm UK guidance; however, in clinically stable patients with undetectable viral loads and CD4 counts above 350 cells/mm³ there is a trend toward doing viral load testing every four months and CD4 counts annually. This results in three visits a year for the clinically stable patient and considerable time and cost saving for the clinic.

A normal CD4 cell count in the blood of a man without HIV infection will be in the range of approximately 400 to 1200 cells/mm³, and 500 to 1600 cells/mm³ in women.

HIV is not the only factor that can affect the CD4 cell count. Studies^{3 4} looking at CD4 cell counts in uninfected men and women found that:

• Women had higher CD4 cell counts than either heterosexual or homosexual men, by an average of 111 cells/mm³.
• Women's CD4 cell counts fluctuate with the menstrual cycle.
• Oral contraceptive use was associated with a lower CD4 cell count.
• Smokers tended to have higher CD4 cell counts, by an average of 143 cells/mm³. 
• CD4 cell counts in the blood decrease following rest. One study found that following 60 minutes of rest, mean CD4 cell counts fell from 1060 to 660 cells/mm³, a decline of 38%. 
• A good night's sleep decreases the numbers of CD4 T-cells and other immune system cells in the blood. However, the following afternoon and evening, a person who slept soundly has higher levels of CD4 cells than a person who experienced wakefulness during the night.
• Acute illness may reduce the CD4 cell count, in some cases below 200 cells/mm³. 

No racial differences were seen in one study⁵, but other studies have found differences.