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Objectives: We studied the frequency and risk factors for loss of long-term non-progressor (LTNP) and HIV controller (HIC) status among patients identified as such in 2005 in the French Hospital Database on HIV (FHDH-ANRS CO4). Methods: We selected patients who were treatment-naïve and asymptomatic in 2005 (baseline). Those with ≥8 years of known HIV infection and a CD4 cell nadir ≥500/mm3 were classified as LTNP and those with ≥10 years of known HIV infection and 90% of plasma viral load (VL) values ≤500 copies/ml in the absence of cART as HIC. cART initiation without loss of status and death from non AIDS-defining causes were considered as competing events. Results: After 5 years of follow-up, 33% (95%CI; 27–42) of 171 LTNP patients and 17% (95%CI; 10–30) of 72 HIC patients had lost their status. In multivariable analyses, loss of LTNP status was associated with lower baseline CD4 cell counts and CD4/CD8 ratios. Only VL was significantly associated with loss of HIC status after adjustment for the baseline CD4 cell count, the CD4/CD8 ratio, and concomitant LTNP status. The hazard ratio for loss of HIC status was 5.5 (95%CI, 1.5–20.1) for baseline VL 50–500 vs ≤50 cp/mL, after adjustment for the baseline CD4 cell count. Conclusions: One-third of LTNP and one-fifth of HIC patients lost their status after 5 years of follow-up, raising questions as to the possible benefits and timing of ART initiation in these populations. [ABSTRACT FROM AUTHOR]