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Virological History Predicts Non-sustained Viral Suppression With Long-Acting Cabotegravir and Rilpivirine Therapy, Independent of Pharmacokinetic Parameters


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Title:
Virological History Predicts Non-sustained Viral Suppression With Long-Acting Cabotegravir and Rilpivirine Therapy, Independent of Pharmacokinetic Parameters
Authors:
Gutiérrez, Félix  
Fernández González, Marta  
Ledesma, Christian
Losada-Echeberría, María  
Barrajón-Catalán, Enrique  
García-Abellán, Javier  
De Stefano, Daria
López, Leandro  
Bello-Perez, Melissa
Padilla, Sergio  
Masiá, Mar
Editor:
Prensa de la Universidad de Oxford
Department:
Departamentos de la UMH::Ingeniería
Issue Date:
2024-09
URI:
https://hdl.handle.net/11000/34431
Abstract:
Background. This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK). Methods. A prospective cohort study was conducted on people with human immunodeficiency virus (HIV, PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB + RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma human immunodeficiency virus type 1 (HIV-1) viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes. Results. Among 173 patients with a median (interquartile range [IQR]) follow-up of 11.1(7.1–13.2) months and 789 pre-dose measurements, 38.7% experienced VL ≥ 20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in 2 cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis (adjusted hazard ratio [AHR]: 1.49 per log10 VL, 95% confidence interval [CI]: 1.04–2.12, P = .027), detectable viremia on oral ART (AHR: 2.45, 95% CI: 1.29–4.65, P = .006), and the level of viral suppression at transition (AHR: 0.38, 95% CI: .19–.75, P = .004). We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models. Conclusions. Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB + RPV LA was linked to preexisting factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.
Keywords/Subjects:
long-acting cabotegravir and rilpivirine
pharmacokinetics
non-sustained viral suppression
viral blips
low-level viremia
Knowledge area:
CDU: Ciencias puras y naturales: Generalidades sobre las ciencias puras
Type of document:
info:eu-repo/semantics/article
Access rights:
info:eu-repo/semantics/closedAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
DOI:
https://doi.org/10.1093/cid/ciae475
Appears in Collections:
Artículos Ingeniería



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