Long-term Evolution of CD4 Count in Patients With a Plasma HIV RNA Persistently <500 copies/mL During Treatment With Antiretroviral Drugs

V Le Moing; R Thiébaut; G Chêne; A Sobel; P Massip; F Collin; MC Meyohas; F Al Kaïed; C Leport; F Raffi; the ANRS CO8 (APROCO/COPILOTE) Study Group


HIV Medicine. 2007;8(3):156-163. 

In This Article

Abstract and Introduction


Background: The increase in CD4 count may reach a plateau after some duration of virological response to highly active antiretroviral therapy (HAART).
Methods: A total of 1281 HIV-infected patients initiating HAART were enrolled in the AntiPROtease (APROCO) cohort. We investigated determinants of increase in CD4 count using longitudinal mixed models in patients who maintained a plasma HIV RNA <500 HIV-1 RNA copies/mL.
Results: A total of 870 patients had a virological response at month 4. The median follow-up time was 57 months. Mean estimated increases in CD4 count in patients with persistent virological response were 29.9 cells/µL/month before month 4, 6.4 cells/µL/month between months 4 and 36, and 0.7 cells/µL/month (not significantly different from 0) after month 36. Three factors were associated with a significantly positive CD4 count slope after month 36: male gender (+0.9), no history of antiretroviral therapy at baseline (+1.7) and baseline CD4 count <100 cells/µL (+2.6). In patients who maintained a virological response after 5 years of HAART, a CD4 count >500 cells/µL was achieved in 83% of those with a baseline CD4 count ≥200 cells/µL and in 45% of those with a baseline CD4 count <200 cells/µL.
Conclusion: The increase in CD4 count reaches a plateau after 3 years of virological response. Even if patients initiating HAART with low CD4 counts still show a CD4 count increase after 3 years, it remains insufficient to overcome immune deficiency in all patients.


The main objective of long-term antiretroviral therapy is to reach and maintain a sufficiently high CD4 cell count to provide the patient with long-term protection against opportunistic infections and cancers. We and others[1,2,3] have shown that the magnitude and duration of the increase in CD4 cell count are mainly driven by the achievement and maintenance of a complete virological response, characterized by a very low level of residual plasma HIV RNA; that is, in routine clinical practice, a viral load under 500 HIV-1 RNA copies/mL, the detection threshold of the less sensitive arrays used to quantify HIV RNA.

The length of time for which the CD4 cell count continues to increase in those patients who maintain a complete virological response is, however, a matter of debate. Some authors have suggested that, after 2 to 3 years of virologically successful therapy, the increase slows down and CD4 cell counts may reach a plateau in most patients.[4,5,6,7] Others have shown a continuous and vigorous increase in the third year of complete virological response and thereafter.[8,9,10] Discrepancies between studies may be a result of insufficient follow up, an insufficient number of patients or inadequate modelling of data. Moreover, in these previous studies, the influence of the degree of previous immunodepression and of other cofactors known or thought to modify immune restoration, such as age,[11] gender[12] and treatment with nonnucleoside reverse transcriptase inhibitors (NNRTIs),[12,13,14] was not explored. To gain more understanding of the history of CD4 cell reconstitution and factors related to long-term antiretroviral treatment-mediated CD4 cell count increase, we studied the long-term evolution of CD4 cell count in a large prospective cohort of treated patients.

More specifically, we investigated whether there is a plateau of CD4 cell count in patients in whom a complete virological response is maintained and, if such a plateau exists, at what time the slope of CD4 cell count becomes zero and whether the plateau is observed in every category of patients, especially in those who initiate potent antiretroviral therapy while their CD4 cell count is very low.


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