Real world evaluation of HIV-1 reservoir and resistance in virologically suppressed people after 52 weeks of treatment with long-acting cabotegravir + rilpivirine.

Abstract

Although long-acting cabotegravir plus rilpivirine (CAB+RPV LA) has demonstrated high efficacy in clinical trials, real-world data on archived resistance and HIV-1 reservoir dynamics remain limited. Archived resistance profile and total HIV-1 DNA were assessed at baseline and over 52 weeks in 36 virologically suppressed participants who switched to CAB+RPV LA, followed at the Polyclinic of Foggia, Italy. Total HIV-1 DNA in whole blood was quantified by real-time PCR. Resistance and APOBEC-context mutations were assessed through the Stanford HIVdb algorithm. At baseline, participants had a median body mass index (BMI) of 26.1 kg/m² and prior virological suppression (VS) of 8.5 years; none of them harboured A6 subtype. Thirty-four participants (94.4%) maintained VS after 52 weeks on CAB+RPV LA, with a stable total HIV-1 DNA (3.5 at baseline versus 3.7 log₁₀ copies/10⁶ CD4 at week 52, p=0.324). Baseline prevalence of NNRTI and INSTI major mutations was 18.2% and 6.5%, respectively. NNRTI prevalence remained constant, while no major INSTI mutations were found at week 52. Excluding APOBEC-context mutations, NNRTI resistance prevalence was about 9% at both time points, while no INSTI major mutations were found. In the two participants who failed CAB+RPV LA, NNRTI resistance was detected at failure; they subsequently regained VS after treatment modification. In this real-world study, a stable HIV-1 DNA over 52 weeks of CAB+RPV LA treatment was observed. A substantial proportion of participants harboured NNRTI or INSTI major mutations, mostly APOBEC-context, without conferring true resistance. These findings emphasize the importance of a careful interpretation of proviral resistance.