Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine.
J Antimicrob Chemother
; 79(5): 1133-1141, 2024 05 02.
Article
en En
| MEDLINE
| ID: mdl-38546974
ABSTRACT
INTRODUCTION:
The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48â weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters.METHODS:
Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways. DOLAM (EudraCT 201500027435) is a Phase 4, randomized, open-label, non-inferiority trial in which virologically suppressed persons with HIV treated with 3DR were assigned (11) to switch to 2DR or to continue 3DR for 48â weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48â weeks. Univariate and multivariate analyses were performed to identify changes in key molecules between both therapy arms.RESULTS:
Switching from 3DR to 2DR showed a multiomic impact on circulating plasma concentration of N-acetylmuramoyl-L-alanine amidase (Q96PD5), insulin-like growth factor-binding protein 3 (A6XND0), alanine and triglyceride (TG) (480). Correlation analyses identified an association among the up-regulation of these four molecules in persons treated with 2DR.CONCLUSIONS:
Untargeted multiomics profiling studies identified molecular changes potentially associated with inflammation immune pathways, and with lipid and glucose metabolism. Although these changes could be associated with potential metabolic or cardiovascular consequences, their clinical significance remains uncertain. Further work is needed to confirm these findings and to assess their long-term clinical consequences.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oxazinas
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Piperazinas
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Piridonas
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Infecciones por VIH
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Lamivudine
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Compuestos Heterocíclicos con 3 Anillos
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2024
Tipo del documento:
Article
País de afiliación:
España