Introducción. Integrase strand transfer inhibitors (INSTIs) are a family of antiretrovirals (ART) used for the treatment of HIV-1 infection, their mechanism of action is based on blocking the integration of proviral DNA into DNA of the host. Objective. To describe the resistance profile to Integrase Strand Transfer Inhibitors -INSTIs- in patients with therapeutic failure to multiple antiretroviral regimens. Methodology. Descriptive cross-sectional study that included 41 records of HIV-1 positive adult patients with multiple failure, who were indicated to perform a genotype test of the integrase region of the HIV-1 pol gene from February 2018 to March 2021. The analysis was carried out in the DeepChek® v2.0 software, for the classification of resistance the HIV Drug Resistance Database (HIVdb) Stanford University v9.5 algorithm (2023/08/22) was followed. Results. 51.2% of the patients were male. The median age at the time of requesting the test was 40 years (IQR 30, 46). 34.1% (14/41) of general resistance was identified. The highest drug resistance was found in Elvitegravir with 26.8% (11/41) followed by Raltegravir at 24.4% (10/41). The most frequently identified primary mutations were G140A/S and Q148H in 35.7% (5/14) each, as well as N155H and E138K in 21.4% (3/14) each. Conclusion The data presented in this study show the importance of acting promptly when suspected virological failure in patients with failure to multiple therapies, which include the use of INSTI; as well as maintaining periodic surveillance of drug resistance in both pretreated patients and those who have not been exposed to ART, which will allow trends to be identified and support the implementation of timely interventions.