Background:  Our objectives were to assess:  the safety of prolonged discontinuation of successful antiretroviral therapy; to measure the percentage of patients who could interrupt their treatment for a minimum of 12 months according to CD4 T-cell nadir level; the median decrease of CD4 T cells; and the effect on dyslipidemia. The end-point was the proportion of subjects maintaining CD4 cell count > 350 cells/mL.

Methods:  Patients with CD4 cells count > 500/mm³ and viral load < 50 copies during > 6 months were enrolled. The immunologic threshold to resume therapy was set to 350/mm³.

Results:  We included 94 patients in the study and followed them for 50 months. At baseline, all had undetectable viral load and their mean CD4 cell count was 866 cells/mL; 47 patients had a CD4 T-cell nadir < 350 cells/mL. An acute retroviral syndrome was observed in 3 patients. Discontinuation was prolonged at least 12 months in 90%, 75%, and 72% of patients with a nadir CD4 T cells > 350, between 200 and 350 and between 100 and 200, respectively, but only in 26% of those with nadir CD4 < 100 cells. Predictive factors to resume therapy were the CD4 T-cell nadir and the level of viral load before HAART. Median decrease of CD4 T cells was 95 cells per months during the 3 first months followed by a plateau in patients with a nadir CD4 T cells < 350/mL. Two patients showed a disease progression (1 Kaposi sarcoma and 1 toxoplasma retinitis), but this progression was associated with a high viral load (> 6 log). The mean percentage of patients with a grade 2 to 4 dyslipidemia dropped from 17% to 5% after interruption. No patient underwent virological failure after HAART re-introduction.

Conclusions:  Prolonged discontinuation in patients with fully suppressed virus and marked immune reconstitution was safe even in patients with a nadir CD4 cell count of between 100 and 350 cells/mL. In patients with very high viral load (> 5.5 log), resuming HAART is warranted whatever the CD4 count level.

Keywords: treatment interruption; cohort study; prognostic factors