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.

CD4 cell counts in uninfected adults

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 looking at CD4 cell counts in uninfected, heterosexual and homosexual 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.

No racial differences were seen in one study (Maini 1996), but other studies have found differences.

A trend towards higher CD4 counts has also been seen in HIV-positive smokers, as compared with non-smokers.

It may be deceptive for an untested person to use their CD4 cell count as a guide to whether or not they may be infected with HIV. A US study of HIV-negative patients admitted to an intensive care unit found that 17% had CD4 counts below 200, and the mean CD4 cell count was 510 cells/mm³ (Aldrich 2000). Acute illness other than HIV infection may also affect the CD4 cell count, but it will not affect the CD4:CD8 ratio, unlike HIV infection.

Only a small percentage of the total CD4 count is in the blood at any one time. The rest are in the tissues and lymph nodes. Changes described above may be due to the movement of CD4 cells between blood and tissues.

CD4 cell counts in HIV infection

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. A study of people with very low CD4 cell counts at Londons Royal Free Hospital found that in 1989 no patient survived with a count of zero, but by 1997 the average (median) survival for people with zero counts was 1.2 years due to improved clinical care (Sabin 1997).

The Swiss Cohort Study found that the average CD4 cell count fell by 46 cells/mm³ per half-year, and that the higher a persons CD4 cell count, the greater the CD4 cell count decline over a six month period (Vanhems 1999). The CD4 cell count appears to decline more rapidly in the year before an AIDS diagnosis, and this is why treatment guidelines recommend that people with CD4 cell counts between 350 and 200 cells/mm³ should consider treatment if their CD4 cell count begins to fall more rapidly (Schellekens 1992).

CD4 cell counts can also be used to predict the risks for particular AIDS conditions such as Pneumocystis pneumonia (PCP), CMV or MAI. This can be extremely useful in deciding who will benefit from prophylactic (preventative) 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 being 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.

CD4 percentage

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.

Some doctors argue that this is potentially the most accurate CD4 test, although it is not very sensitive to small changes. It can be particularly useful if you receive a CD4 result that you are not expecting, for example a sudden drop. If the immune system is being damaged by HIV, then one could expect the percentage of all lymphocytes to have decreased. However, if the percentage stays the same it is more likely that you had an infection which your immune system was dealing with, which caused your CD4 count to drop.

References

Aldrich J et al. The effect of acute severe illness on CD4+ lymphocyte counts in nonimmunocompromised patients. Arch Intern Med 160: 5, 2000.

Lepri AC et al. The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts in advanced HIV infection. AIDS 12: 1639-1642, 1998.

Machado SG et al. On the use of laboratory markers as surrogates for clinical endpoints in the evaluation of treatment for HIV infection. J Acquir Immune Defic Syndr 3: 1065-1073, 1990.

Maini MK et al. Reference ranges and sources of variability of CD4 counts in HIV-seronegative women and men. Genitourin Med 72: 27-31, 1996.

Sabin CA et al. Survival after a very low (less than 5 x 10(6)/1) CD4+ T-cell count in individuals infected with HIV. AIDS 11: 1123-1127, 1997.

Schellekens PT et al. Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV-1 phenotype. AIDS 6: 665-669, 1992.

Vanhems P et al. Association between the rate of CD4+ T cell decrease and the year of Human Immunodeficiency Virus (HIV) type 1 seroconversion among persons enrolled in the Swiss HIV Cohort Study. J Infect Dis 180: 1803-1808, 1999.