Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis.
Clin Infect Dis
; 79(1): 189-195, 2024 Jul 19.
Article
en En
| MEDLINE
| ID: mdl-38207125
ABSTRACT
BACKGROUND:
Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation.METHODS:
We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low.RESULTS:
Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels.CONCLUSIONS:
This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piridonas
/
Infecciones por VIH
/
VIH-1
/
Insuficiencia del Tratamiento
/
Fármacos Anti-VIH
/
Farmacorresistencia Viral
/
Rilpivirina
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Clin Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos