Literature Commentary by Dr. John G. Bartlett: CD4+ Count Normalization With HAART, January 2008

John G. Bartlett, MD


January 14, 2008

Mocroft A, Phillips AN, Gatell J, et al., for the EuroSIDA study group. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet. 2007;370:407-413. The goal of the study was to determine CD4+ cell count increases in patients who have virologic suppression.

Methods: The study used data from the EuroSIDA cohort, which is a European study of 14,262 patients with HIV infection in 92 centers in Europe, Israel, and Argentina. Patients were included if they had at least 2 consecutive HIV viral loads < 50 HIV RNA copies/mL; and CD4+ cell counts before starting HAART and every 6 months thereafter.

Results: The median CD4+ count at initiation of HAART was 204 cells/microliter (mcL) and the greatest median yearly increase in CD4+ count was approximately 100 cells/mcL, which occurred in the first year after starting HAART. Smaller yearly increases in CD4+ counts averaging about 50 cells/mcL/year continued over 4 years in those with CD4+ counts < 350 cells/mcL at baseline. The only group that did not have a significant increase was those who initiated HAART with CD4+ count
> 500 cells/mcL. These results are shown in the Table .

Multivariate analysis showed no significant effect on the yearly increase in CD4 cell count based on age, change in CD4+ cell count since starting HAART, the peak HIV viral load or CD4+ cell count at baseline.

Conclusion: The authors conclude that normal CD4+ cell counts can be achieved with viral suppression if it is maintained for a sufficient period.

Comment: Previous studies have shown that the increase in CD4+ cell count diminishes with sequential analyses during HIV viral suppression as shown in this report. However, some have suggested a plateau with no further increases after 4 years,[1] and others have shown a subgroup of about 40% of patients who had no further increases after 4 years.[2,3] Some of the differences may be related to the size of the cohort, failure to make these measurements with confirmed viral load suppression, and/or the use of a higher threshold for defining viral suppression. Of note in the context of strategies for "when to start," the results of this study showed that patients who started HAART with a CD4+ count > 350 cells/mcL had CD4+ cell counts approaching the levels seen in patients without HIV infection after 3 years of HAART. However, there was no ceiling for increases with longer duration of HAART in those who started with lower CD4+ cell counts.


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