Risk Factors and Therapeutic Consequences of Virologic Failure With Long-Acting Cabotegravir Plus Rilpivirine in the Dat'AIDS Cohort.

BACKGROUND

Long-acting cabotegravir plus rilpivirine (CAB + RPV LA) is highly effective as maintenance therapy in virologically suppressed people with HIV (PWH), but virologic failure (VF) may lead to resistance and compromise future antiretroviral options.

METHODS

We conducted a multicenter observational study within the French Dat'AIDS cohort, including HIV-1 virologically suppressed adults who switched to CAB + RPV LA between December 2021 and December 2023. VF was defined as two consecutive HIV-1 RNA >50 copies/mL or one >200 copies/mL. Remaining options were interpreted using ANRS and Stanford algorithms. Cox models identified factors associated with VF.

RESULTS

Among 2,196 participants followed for a median of 13 months, VF occurred in 42 individuals (1.9%) after a median of 103 days. Among 26 VF cases undergoing genotype, resistance emerged in 13 (50%), with susceptibility maintained more often for doravirine (ANRS 92%, Stanford 96%) than for dolutegravir/bictegravir (ANRS 58%, Stanford 65%). Resistance also emerged during low-level viremia or transient rebound with re-suppression (7/13 cases). In multivariable analysis, higher BMI (aHR 1.07; 95%CI 1.01-1.14), nadir CD4 < 200 cells/mm3 (aHR 2.44; 1.31-4.56), and prior suppression <12 months (aHR 2.39; 1.01-5.19) were independently associated with VF. Historical CAB and RPV RAMs also increased VF risk.

CONCLUSIONS

CAB + RPV LA was associated with low incidence of VF and rare resistance emergence. When resistance occurred, it primarily compromised bictegravir/dolutegravir rather than doravirine. Low nadir CD4, shorter prior suppression, higher BMI, and historical CAB and/or RPV RAMs support individualized candidate selection and early resistance testing, even during low-level viremia.