CD4 percentages, along with CD4 cell counts, could be of benefit in helping patients decide when to start antiretroviral therapy, according to a study published in the 15th September edition of The Journal of Infectious Diseases. In particular, they suggest that patients with a CD4 cell count above 350 cells/mm3 but a low CD4 percentage could benefit from starting HIV treatment earlier than recommended in current guidelines.
CD4 cell counts are measured by counting the number of CD4 T-cells in every cubic millimetre of blood. While these give a useful estimate of the strength of the immune system, some experts believe that the CD4 percentage gives a more accurate measure of how much immune damage has been done. CD4 percentages refer to the number of CD4 T-cells within every 100 lymphocytes, the subset of white blood cells that includes T-cells and B-cells.
Although HIV-positive patients with CD4 cell counts below 200 cells/mm3 are known to benefit from starting antiretroviral therapy, the best time for patients with CD4 cell counts above this value to start treatment is uncertain. Current guidelines recommend that patients wait until CD4 cell counts have fallen to below 350 cells/mm3 before considering starting treatment, in order to avoid running the risk of developing drug side-effects and resistance.
To discover whether CD4 percentages could provide additional information on treatment inititiation, investigators from Nashville, United States examined the rates of opportunistic infections, AIDS or death in a cohort of 788 patients starting highly active antiretroviral therapy (HAART). AIDS was defined according to the 1993 Centers for Disease Control and Prevention criteria, with the exception of CD4 cell counts being below 200 cells/mm3.
At the start of the study, the median CD4 cell count was 255 cells/mm3 and the CD4 percentage was 17%. HIV-negative people tend to have CD4 cell counts between 400 and 1600 cells/mm3 and CD4 percentages around 40%.
Overall, the investigators found that patients with CD4 percentages below 17% at the start of the study progressed more rapidly than those with higher CD4 percentages (p < 0.001). The median length of follow-up was 103 weeks.
Other factors associated with disease progression included viral load (p < 0.001) and race, with non-white patients being 1.54 times more likely to progress than white patients (p = 0.014).
Among the patients with CD4 cell counts above 350 cells/mm3, a baseline CD4 percentage below 17% was also found to be linked to more rapid disease progression (p = 0.03). It was also the most reliable predictor of disease progression in this group, corresponding to a 3.57-times greater risk of progression than those with higher percentages (p = 0.045).
“These findings suggest that CD4 lymphocyte percentage may assist in identifying persons with higher absolute CD4 lymphocyte counts who would benefit from early initiation of HAART,” write the investigators.
“Although additional studies with larger populations are needed to confirm these findings, they are consistent with those from studies from the pre-HAART era, which found CD4 lymphocyte percentage to be a better predictor of disease progression than absolute CD4 lymphocyte count,” they add.
In contrast, the researchers did not see a significant association between CD4 percentage and disease progression when they looked at all patients with a CD4 cell count above 200 cells/mm3 at baseline. This suggests that CD4 percentage is not of additional benefit in identifying patients who should start treatment when CD4 cell counts are between 200 and 350 cells/mm3.
Similarly, CD4 percentage did not provide additional information on the risk of disease progression in patients with CD4 cell counts below 200 cells/mm3 at the start of the study. “This … demonstrates the very strong predictive power of absolute CD4 lymphocyte counts less than 200 lymphocytes/mm3 in determining the risk of disease progression,” they explain.
In an accompanying editorial commentary, Miguel Goicoechea and Richard Haubrich write, “although absolute CD4 lymphocyte counts and CD4 lymphocyte percentages provide similar information and are highly correlated, these correlations are not perfect.
“Differences between absolute CD4 lymphocyte count and CD4 lymphocyte percentage may represent a type of immune discordance.”
Goicoechea M et al. CD4 lymphocyte percentage versus absolute CD4 lymphocyte count in predicting HIV disease progression: an old debate revisited. J Infect Dis 192: 945-947, 2005.
Hulgan T et al. CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiation highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3. J Infect Dis 192: 950-957, 2005.