Although integrase strand transfer inhibitors (INSTIs) are widely used in HIV-1 group M (HIV-1/M) infections, little is known about their efficacy against genetically divergent HIV-1 group O (HIV-1/O) strains. Previous phenotypic works have demonstrated the variable susceptibility of HIV-1/O strains, depending on INSTI drugs. Clinical data are very limited and obtained from a few patients. OBJECTIVES: To investigate the virological success rate of an INSTI-based combination of antiretroviral therapy (cART) in a large population of HIV-1/O-infected patients, and to describe resistance-associated mutations (RAM) at virological failure. METHODS: The virological response of 39 patients receiving INSTI-based cART during their follow-up was analysed i) at the last point of the first INSTI initiation and ii) at their most recent visit. RAM analysis was performed at virological failures. Resistance interpretation was based on the French National Agency of Research on AIDS and viral hepatitis (ANRS) rules. RESULTS: Virological success at both time points of analysis was high, with more than 87% of the patients with undetectable plasma viral load. Among the six patients with virological failure, three selected RAM described for HIV-1/M resistance, and two had already RAM, before INSTI initiation. CONCLUSION: Our results show that HIV-1/O infected patients receiving INSTI-based cART presented a high rate of virological success whatever their previous lines; we have also shown that resistance rules for HIV-1/M could be considered when failure occurs. These data are of importance especially in the context of WHO recommendations for a wider use of this class.