Primary and secondary resistance of HIV-1 to integrase inhibitors in Cuban patients infected with multidrug-resistant HIV strains

Abstract

Background: Cuban studies show high levels of viral resistance in treated and untreated patients. In 2017, dolutegravir was introduced as a rescue therapy in Cuba, and in 2018 as first-line regimens. The aim of this study was to determine the primary and secondary resistance of HIV-1 to dolutegravir in Cuban patients with multiple resistances. Methods: The sample consisted of 29 patients, of which 23 had not been treated with dolutegravir. The viral RNA isolated from plasma was amplified and the fragment of the pol gene encoding viral integrase (3854-5981bp) was sequenced. The viral subtype of the 29 viruses was determined. Results: No primary resistance mutations to dolutegravir were detected in any patient. The polymorphic positions found with greater frequency in the treated patients were: 112 and 119 (both with 73.9%), 125 (69.5%), and 201 (78.2%). Virological suppression was achieved in 18 out of 23 patients (78.2%) and in 14 out of 23 (60.8%) at three and six months after the start of treatment, respectively. Of the six patients who had received dolutegravir prior to this study, four (66.7%) developed resistance to integrase inhibitors. The subtypes found were: B (41%), CRF19_cpx (24%), CRF18_cpx and C (both 14%), and G (7%). Conclusion: Primary resistance to DTG was not detected, while secondary resistance was high in those patients who received a single daily dose of the antiviral. It is necessary to delve into the role of some polymorphisms, more frequent in certain subtypes, and their contribution to primary resistance.