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

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.

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.

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%.

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.

NCT06661317.