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Background: Since the release of protease inhibitors, only 2 randomized trials in the late 1990s have re-assessed the potency of dual nucleoside reverse transcriptase inhibitor (NRTI) combination (2N) as a maintenance strategy for patients whose HIV RNA was suppressed by tri-therapy. The objective of this study was to describe the characteristics of patients who exhibited durable virologic suppression while receiving 2N., Methods: A retrospective study was conducted in 2 French hospitals. Using electronic medical records, we identified all HIV-1-infected patients treated with tenofovir/emtricitabine or abacavir/lamivudine (without a third agent) between 2005 and 2012., Results: Out of 1,255 patients, 37 (3%) received a 2N regimen and were included in this study. All received a fixed-dose combination of either tenofovir/emtricitabine (n = 31) or abacavir/lamivudine (n = 6). This regimen was a first-line (n = 8) or a simplification (n = 29) strategy. The total follow-up for patients receiving 2N was 123 patient-years (median, 3.2 years; interquartile range [IQR], 1.3-5.1). At the last visit, 33 of 37 patients were continuing with 2N and had HIV RNA <50 copies/mL (success rate of 89%, snapshot analysis). These patients had received early treatment (median CD4+ nadir, 340/mm3) and had a low HIV RNA zenith (median, 3.9 log/mL) and a low HIV DNA level (median, 2.5 log copies/106 peripheral blood mononuclear cells). Four patients, treated with tenofovir/emtricitabine in the simplify cation group, experienced viral failure., Conclusions: These results suggest that, in selected patients, a 2N fixed-dose combination is able to maintain viral suppression durably. Such a simple strategy could reduce both the constraints and side effects experienced by patients and the costs for the community.