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- Title
Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure.
- Authors
Orkin, Chloe; Schapiro, Jonathan M; Perno, Carlo F; Kuritzkes, Daniel R; Patel, Parul; DeMoor, Rebecca; Dorey, David; Wang, Yongwei; Han, Kelong; Eygen, Veerle Van; Crauwels, Herta; Ford, Susan L; Latham, Christine L; Clair, Marty St.; Polli, Joseph W; Vanveggel, Simon; Vandermeulen, Kati; D'Amico, Ronald; Garges, Harmony P; Zolopa, Andrew
- Abstract
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 ≥30 kg/m2 were associated with an increased risk of CVF (P <.05 adjusted incidence rate ratio), with participants with ≥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 ≥2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤first quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA.
- Subjects
HIV infections; COMBINATION drug therapy; GENETIC mutation; PATIENT selection; VIRAL load; MULTIVARIATE analysis; REVERSE transcriptase inhibitors; RILPIVIRINE; ANTIRETROVIRAL agents; DISEASE incidence; TREATMENT failure; RISK assessment; FACTOR analysis; DESCRIPTIVE statistics; RESEARCH funding; PREDICTION models; BODY mass index; HIV; THERAPEUTICS; EVALUATION
- Publication
Clinical Infectious Diseases, 2023, Vol 77, Issue 10, p1423
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciad370