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, 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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Cite this: Literature Commentary by Dr. John G. Bartlett: CD4+ Count Normalization With HAART, January 2008 - Medscape - Jan 14, 2008.