The Epidemiology of HIV‐1 Resistance to Two‐Drug Regimens in Multicenter Cohort From Poland—A Cross‐Sectional Study

ABSTRACT Background and Aims Concerns about antiretroviral therapy failure are growing among people with HIV receiving two‐drug regimens, as these schemes include fewer active agents, while the prevalence of transmitted resistance in HIV‐1 continues to increase. Therefore, we aimed to assess the epidemiology of HIV‐1 drug resistance mutations to the most commonly used two‐drug regimens, consisting of oral dolutegravir plus lamivudine and injectable cabotegravir plus rilpivirine. Methods In a multicenter, cross‐sectional study conducted from January 2023 to March 2024, the frequency of HIV‐1 resistance mutations to antiretrovirals was evaluated. Analyses were performed for drugs used in two‐drug regimens, separately in treatment‐naïve and treatment‐experienced patients. Results In a total of 333 patients included, 82% were treatment‐naïve and sub‐subtype A6 was responsible for 49.8% of infections. In treatment naïve patients, the frequency of transmitted major mutations to at least one agent ranged from 1.5% for dolutegravir plus lamivudine to 4.4% for cabotegravir plus rilpivirine. In treatment‐experienced individuals with antiretroviral failure or who interrupted the treatment, the frequency of acquired major mutations to at least one agent was 6.7% for cabotegravir plus rilpivirine and 11.7% for dolutegravir plus lamivudine. In the latter subgroup, the frequency of any acquired resistance mutations (major and accessory) reached 16.7–23.3%. Conclusions The integrase genotyping provides wide insight in a variable infection epidemiology and new therapeutic schemes. In our cohort, transmitted resistance to two‐drug regimens in treatment‐naïve individuals appears uncommon, with the frequency of 0.7–4.4%. However, in patients who interrupted the treatment or who experienced virological failure, all acquired resistance mutations are present in almost one‐fourth of individuals, thus selective pressure from antiretroviral therapy warrants continuous surveillance. ClinicalTrials.gov Identifier NCT06661317.