Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir plus Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure

Background Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB + RPV LA) were expanded to include data beyond week 48, additional covariates, and additional participants. Methods Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using 2 populations. Two models were conducted in each population-baseline factor analyses exploring factors known at baseline and multivariable analyses exploring baseline factors plus postbaseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks postinjection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). Results Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and body mass index & GE;30 kg/m(2) were associated with an increased risk of CVF (P < .05 adjusted incidence rate ratio), with participants with & GE;2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. Conclusions The presence of & GE;2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index & GE;30 kg/m(2)) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (& LE;first quartile) did not improve the prediction of CVF beyond the presence of a combination of & GE;2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA. Confirmed virologic failure occurred in 1.4% of long-acting cabotegravir + rilpivirine participants up to 3 years on study. Having & GE;2 baseline factors (rilpivirine resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and/or body mass index & GE;30 kg/m(2)) was associated with increased failure risk, consistent with prior analyses.