Background: Incomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virologic failure and the response to a salvage regimen after 48 weeks. Methods: This work was a cross-sectional, retrospective, analytical study based on data collected from medical records and genotyping tests between 2006 and 2016. The sample consisted of data on individuals living with HIV (PLWH) from three major reference centers. Results: A total of 184 patients were included in the data analysis. Viral subtype B was the most common (81.3%) as well as M184 V/I (85.3%) and K103 codon mutations (65.8%). Forty-eight weeks after switching to a salvage regimen, 67.3% of patients achieved an undetectable viral load. Discussion: The number of mutations associated with nucleos(t)ide reverse transcriptase inhibitors (NRTI(t)s) did not affect virologic suppression (9.3% for zero NRTI(t)-associated mutations vs 48.6% for 1–2 NRTI(t)-associated mutations vs 42.1% for ≥3 NRTI(t)-associated mutations, p = 0.179). An ARV time (the beginning of the first ARV regimen up to genotyping) of > 36 months was a protective factor for detectable viral load (PR = 0.60, 95% CI = 0.39–0.92, p = 0.020) and a risk factor for developing ≥3 NRTI(t)-associated mutations (PR = 2.43, 95% CI 1.38–4.28, p = 0.002). Conclusions: We found that extensive resistance to NRTI(t)s at the time of the first virologic failure did not impact virologic suppression at 48 weeks after switching to a second-line therapy based on NRTI(t)s plus protease inhibitors.