Effectiveness of bi-monthly long-acting injectable cabotegravir and rilpivirine as maintenance treatment for HIV-1 in the Netherlands: results from the Dutch ATHENA national observational cohort

Background: Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands. Methods: We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands. In the primary analysis, we matched individuals who commenced cabotegravir and rilpivirine and had no history of virological failure (ie, one or more measurements of a plasma HIV RNA ≥1000 copies per mL; hereafter referred to as exposed) 1:2 with individuals using oral antiretroviral therapy (ART; hereafter referred to as unexposed). We assessed the effectiveness of cabotegravir and rilpivirine using restricted mean survival time (RMST) until loss of virological control (one or more measurements of plasma HIV RNA ≥200 copies per mL). In the secondary analysis, we assessed loss of virological control in individuals who commenced cabotegravir and rilpivirine with previous virological failure or unsuppressed HIV-1 RNA at cabotegravir and rilpivirine initiation, or both. Findings: In primary analysis, 585 exposed and 1170 unexposed individuals were included between Feb 27, 2018, and Aug 17, 2023. Median follow-up was 1·3 years (IQR 0·9 to 1·7). 14 exposed (2%) and 29 unexposed (2%) individuals had a loss of virological control, with no difference in RMST (difference=0·026, 95% CI –0·029 to –0·080). Seven (50%) exposed individuals re-suppressed without a regimen change. Seven (50%) switched ART, and six (43%) of 14 had documented integrase strand transfer inhibitor (INSTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. No unexposed individuals switched ART after loss of virological control. In the secondary analysis, 105 individuals were included between July 1, 2016, and Aug 17, 2023. During a median follow up of 1·4 years (IQR 0·8 to 1·8), nine (9%) had a loss of virological control, of which five (56%) had INSTI or NNRTI resistance. Interpretation: Switching to cabotegravir and rilpivirine was not associated with a higher risk of loss of virological control among individuals without previous virological failure compared with oral ART. The high risk of loss of virological control among individuals with previous virological failure or an unsuppressed HIV-1 RNA at cabotegravir and rilpivirine initiation warrants more careful monitoring. Funding: Dutch Ministry of Health, Welfare, and Sport.