Résumé : Background: Combination antiretroviral therapy (cART) has been shown to reduce mortality and morbidity in patients with HIV. As viral replication falls, the CD4 count increases, but whether the CD4 count returns to the level seen in HIV-negative people is unknown. We aimed to assess whether the CD4 count for patients with maximum virological suppression (viral load <50 copies per mL) continues to increase with long-term cART to reach levels seen in HIV-negative populations. Methods: We compared increases in CD4 counts in 1835 antiretroviral-naive patients who started cART from EuroSIDA, a pan-European observational cohort study. Rate of increase in CD4 count (per year) occurring between pairs of consecutive viral loads below 50 copies per mL was estimated using generalised linear models, accounting for multiple measurements for individual patients. Findings: The median CD4 count at starting cART was 204 cells per μL (IQR 85-330). The greatest mean yearly increase in CD4 count of 100 cells per μL was seen in the year after starting cART. Significant, but lower, yearly increases in CD4 count, around 50 cells per μL, were seen even at 5 years after starting cART in patients whose current CD4 count was less than 500 cells per μL. The only groups without significant increases in CD4 count were those where cART had been taken for more than 5 years with a current CD4 count of more than 500 cells per μL, (current mean CD4 count 774 cells per μL; 95% CI 764-783). Patients starting cART with low CD4 counts (<200 cells per μL) had significant rises in CD4 counts even after 5 years of cART. Interpretation: Normalisation of CD4 counts in HIV-infected patients for all infected individuals might be achievable if viral suppression with cART can be maintained for a sufficiently long period of time. © 2007 Elsevier Ltd. All rights reserved.