Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine
de Lazzari, Elisa (Universitat de Barcelona)
Negredo Puigmal, Eugènia (Institut Germans Trias i Pujol)
Domingo, Pere (Institut de Recerca Sant Pau)
Tiraboschi, Juan Manuel (Hospital Universitari de Bellvitge)
Ribera, Esteve (Hospital Universitari Vall d'Hebron)
Abdulghani, Nadia (Hospital Arnau de Vilanova (València))
Alba, Verónica (Universitat Rovira i Virgili)
Fernández-Arroyo, Salvador (Universitat Rovira i Virgili)
Vilades, Consuelo (Universitat Rovira i Virgili)
Peraire, Joaquim (Universitat Rovira i Virgili)
Gatell, José M. (Universitat de Barcelona)
Blanco, José L. (Instituto de Salud Carlos III)
Vidal, Francesc (Universitat Rovira i Virgili)
Rull, Anna (Universitat Rovira i Virgili)
Martínez, Esteban (Universitat de Barcelona)

Data:	2024
Resum:	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 48weeks 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 (1:1) to switch to 2DR or to continue 3DR for 48weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48eeks. 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) (48:0). 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.
Ajuts:	Instituto de Salud Carlos III PI19/01337
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adult ; Alanine ; Anti-HIV Agents ; Antiretroviral Therapy, Highly Active ; Drug Substitution ; Female ; Heterocyclic Compounds, 3-Ring ; HIV Infections ; Humans ; Lamivudine ; Lipidomics ; Male ; Metabolomics ; Middle Aged ; Multiomics ; Oxazines ; Piperazines ; Plasma ; Proteomics ; Pyridones ; Triglycerides
Publicat a:	Journal of antimicrobial chemotherapy, Vol. 79 Núm. 5 (january 2024) , p. 1133-1141, ISSN 1460-2091

DOI: 10.1093/jac/dkae083
PMID: 38546974

9 p, 629.7 KB

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