Absolute CD4 Versus CD4 Percentage: Which Is the Better Measure for Predicting the Risk of Opportunistic Illnesses? 

This work was first presented in part at the 10th Conference on Retroviruses and Opportunistic Illnesses (10^th CROI) in Boston, MA (February 2003).

Early studies done before the availability of HAART suggested that CD4 percent (%) was a more useful prognostic measure than the absolute CD4 count. Current treatment guidelines recommend consideration of CD4 cell percentage as well as CD4 cell count in therapeutic decisions.

The relative value of CD4 cell count compared with CD4 cell percentage in predicting risk of AIDS-defining illnesses (ADIs) in the post-HAART era is unknown.

Data from an observational clinical cohort of adult HIV-infected patients were used to assess the risk of developing an ADI associated with specific absolute CD4 counts (CD4) and CD4%'s (CD4%) using all CD4-CD4% pairs obtained after January 1996.

The incidence of developing an ADI was assessed over a maximum of 6 months after the CD4-CD4% pair was obtained. Using multivariable negative binomial regression, the incidence rate ratio (IRR) for developing an ADI by CD4 and CD4% categories was computed.

A total of 15,736 CD4-CD4% pairs from 2185 patients who developed 608 ADIs was analyzed. The IRR for developing an ADI by absolute CD4 was 17.9 events/100 person-years for <50 cells/mm3, 6.2 for 50-100 cells/mm3, and 2.7 for 100-200 cells/mm3, compared with the referent stratum of 200-350 cells/mm3.

Without adjustment for absolute CD4, the IRR was 14.4 for CD4% <7%, 3.7 for 7-14%, 1.9 for 15-21%, compared with the referent stratum of >21%.

However, in a multivariable analysis adjusting for absolute CD4, CD4%, and other clinical and demographic variables, the absolute CD4 but not the CD4% was associated strongly with developing an ADI.

In conclusion, the authors write, “The results suggest that CD4% adds little further predictive information after accounting for the absolute CD4 count for the short-term risk of developing an ADI.”

“The absolute CD4 count is the more important measure of immune status and is preferred over the CD4% for making treatment decisions in HIV-infected adults.”

Distribution of Absolute CD4 Count by CD4% Among 15,736 CD4-CD4% Pairs From 2185 Patients

Discussion

Discordance between the absolute CD4 count and the CD4% frequently complicates treatment decisions regarding the need for opportunistic illness prophylaxis, use of antiretroviral therapy, and determination of prognosis.

Although CD4-CD4% pairs are frequently concordant, an unexpectedly high or low CD4% can occur with a particular absolute CD4, making it difficult to assess the subsequent risk of clinical disease.

The current analysis of CD4-CD4% pairs obtained during the clinical care of adult HIV-infected patients followed in a large observational clinical cohort indicates that the absolute CD4 count is the surrogate measure that is most predictive of subsequent short-term risk of developing an ADI, and that the CD4% adds relatively little additional information that would change a treatment decision based on the absolute CD4 count. [emphasis added--Ed]

It is important to note that these data are based on patients followed in an observational cohort who were receiving treatment according to current guidelines for HIV-1-infected individuals, which include consideration of the CD4%. Thus, these data must be interpreted cautiously and not used to alter treatment recommendations.

Earlier studies done before the availability of HAART suggested that CD4% was a more useful prognostic measure. These studies in homosexual men assessed the risk of ADI from 1-3 years after the initial absolute CD4 and CD4% measurement. Of note, these patients had higher CD4 counts than in the Johns Hopkins study.

Another possible reason for the discordance between the present study and previous work is the increased accuracy of the measurement of CD4 cells in the HAART era compared with the pre-HAART era. CD4 counts are now direct measurements and no longer calculated from the total lymphocyte count.

In summary, the authors write, “Our results suggest that the absolute CD4 count may be the more useful measure for decisions regarding use of opportunistic infection prophylaxis and antiretroviral therapy, as well as assessment of prognosis.

“Although it was previously obtained because it was necessary to calculate the absolute CD4, the CD4% adds little additional independent information. It is possible, however, that the CD4% may be useful in patients with extremely discordant CD4-CD4% values.”

Johns Hopkins University School of Medicine, Baltimore, MD.

08/02/04

Reference
K A Gebo and others. Absolute CD4 Vs. CD4 Percentage for Predicting the Risk of Opportunistic Illness in HIV Infection. Journal of Acquired Immune Deficiency Syndromes 36(5): 1028-1033. August 15, 2004.