By Liz Highleyman

Absolute CD4 cell count is the most commonly monitored measure of immune function in people with HIV. According to current U.S. federal HIV treatment guidelines, antiretroviral therapy should be considered when a person's CD4 count falls below 350 cells/mm3, while a level below 200 cells/mm3 indicates a diagnosis of AIDS.

However, CD4 cell percentage may also play a role in guiding decisions about treatment, according to a study published in the February 1, 2007 issue of the Journal of Infectious Diseases. (A CD4 percentage of about 40% is considered normal.)

In the present study, researchers sought to characterize the predictive utility of CD4 percentage. They performed an observational study of participants in the Collaborations in HIV Outcomes Research/US (CHORUS) cohort who started their first HAART regimen between 1997 and 2004 and received at least 30 days of therapy.

Results

• The analysis included 1891 participants with a median age of 38 years; 89% were men, 72% were white, and 18% were African-American.

• Before starting HAART, the mean baseline CD4 cell count was 240 cells/mm3, the mean CD4 percentage was 16%, and 29% had progressed to AIDS.

• After a follow-up period of 55 months (IQR 23-83 months), 468 subjects (25%) experienced disease progression, defined as a new AIDS-defining event or death.

• In a multivariable analysis including age, race, sex, HIV RNA level, prior antiretroviral therapy, probable route of infection, prior AIDS-defining events, absolute CD4 count, and CD4 percentage, the following factors independently predicted disease progression:

- prior antiretroviral therapy (P < 0.0001);
- injection drug use (P = 0.04);
- lower baseline absolute CD4 cell count (P = 0.002);
- lower baseline CD4 cell percentage (P = 0.002).

Conclusion

In conclusion the authors wrote, "[CD4 percentage] at initiation of the first HAART regimen predicted disease progression independent of absolute CD4 [count]."

In their discussion, the researchers noted that while both absolute CD4 cell count and CD4 percentage predicted disease progression, the 2 measures did not always correspond.

That is, some patients with relatively high absolute CD4 counts but low CD4 percentages experienced more disease progression than subjects with low CD4 cell counts but high CD4 percentages. For example, a patient with a baseline absolute CD4 count of 350 cells/mm3 but a CD4 percentage of 14% was at higher risk of disease progression than one with an absolute CD4 count of 200 cells/mm3 but a CD4 percentage of 28%. Moreover, individuals with the same absolute CD4 counts had a variable risk of progression depending on their CD4 percentages.

Thus, the authors said, CD4 percentage may be used as an additional factor to help determine the optimal timing of HAART. These results suggest that some patients with low CD4 percentages may benefit from starting HAART earlier, even if their absolute CD4 counts are not yet at the recommended threshold for initiating therapy.

02/13/07

Reference
T Hulgan, B E Shepard, S P Raffanti, and others. Absolute Count and Percentage of CD4+ Lymphocytes Are Independent Predictors of Disease Progression in HIV-Infected Persons Initiating Highly Active Antiretroviral Therapy. Journal of Infectious Diseases 195(3): 425-431. February 1, 2007.