Trough concentrations of cabotegravir and rilpivirine and their association with detectable viral load in people with HIV on long-acting treatment

Abstract

Background Cabotegravir (CAB) and rilpivirine (RPV) constitute the first complete non-oral ART regimen for HIV-1 treatment. Due to virologic failure (VF) with resistance in clinical trials, concerns persist regarding broader use in clinical practice. In particular, the role of trough drug concentrations in relation to viremia and VF remains unclear. This study explored the association between CAB and RPV trough concentrations in a retrospective, single-center study. Methods We retrospectively analyzed data from the HIV research and clinical care center MVZ M & uuml;nchen am Goetheplatz, Germany. Inclusion criteria were CAB and RPV long-acting therapy every 8 weeks without additional ART and availability of drug concentrations within 7 days before the next administration. A modified Wilcoxon test assessed differences in concentrations between samples with HIV-1 RNA < 20 vs. >= 20 copies/mL. Odds ratios (ORs) were estimated using generalized estimation equation (GEE) models, and ROC analysis identified potential alternative drug concentration thresholds. Findings A total of 737 samples from 185 individuals were included. Median CAB concentrations were 1,480 <mu>g/L (IQR: 1,097-1,955) vs. 1,180 mu g/L (879-1,570) for samples with HIV-1 RNA levels < 20 copies/mL vs. >= 20 copies/mL, respectively (p = 0.001); for RPV, 77 <mu>g/L (53-107) vs. 63 mu g/L (47-87) (p = 0.001). Using ROC-derived thresholds, low concentrations of CAB (< 1,240 <mu>g/L) or RPV (< 76 <mu>g/L) were found in 11.5% and 25.4% of samples, respectively, and associated with ORs of 2.4 (1.5-4.0) and 2.3 (1.4-3.8) for HIV-1 RNA >= 20 copies/mL. Interpretation Lower CAB and RPV concentrations were associated with viremia, particularly using the ROC-derived thresholds. Among individuals with VF and available drug concentration data, 87.5% had at least one drug below these thresholds. Further research on therapeutic drug monitoring is warranted.