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High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients

2022-11-18Artigo científico Acesso aberto
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dc.contributor.authorBártolo, Inês
dc.contributor.authorMoura, Ines
dc.contributor.authorGonçalves, Paloma
dc.contributor.authorDiniz, Ana Rita
dc.contributor.authorBorrego, Pedro
dc.contributor.authorMartin, Francisco
dc.contributor.authorFigueiredo, Inês
dc.contributor.authorGomes, Perpétua
dc.contributor.authorGonçalves, Maria Fátima
dc.contributor.authorAlves, Américo
dc.contributor.authorAlves, Nuno
dc.contributor.authorCaixas, Umbelina
dc.contributor.authorVaz-Pinto, Inês
dc.contributor.authorBarahona, Isabel
dc.contributor.authorMelo, Teresa M. V. D. Pinho E
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2023-08-21T11:44:33Z
dc.date.available2023-08-21T11:44:33Z
dc.date.issued2022-11-18
dc.description.abstractIntegrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection,given the limited number of drugs active against this virus. While the clinical efficacy of raltegravirand dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-β-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBártolo, I.; Moranguinho, I.; Gonçalves, P.; Diniz, A.R.; Borrego, P.; Martin, F.; Figueiredo, I.; Gomes, P.; Gonçalves, F.; Alves, A.J.S.; et al. High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients. Int. J. Mol. Sci. 2022, 23, 14300. https://doi.org/ 10.3390/ijms232214300pt_PT
dc.identifier.doi10.3390/ijms232214300pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.5/28127
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationThis work was supported by Fundação para a Ciência e Tecnologia (FCT), Portugal, Aga Khan Development Network (AKDN)–Portugal Collaborative Research Network in Portuguese speaking countries in Africa (project 332821690). CQC is supported by FCT through projects UIDB/00313/2020 and UIDP/QUI/00313/2020, co-funded by COMPETE2020-UE. iMed.ULisboa, Faculdade de Farmácia da Universidade de Lisboa, Portugal, is supported by FCT through projects UIDB/04138/2020 and UIDP/04138/2020. Inês Bártolo is supported by FCT through Norma Transitória–DL57/2016/CP1376/CT0012. Ana Rita Diniz (SFRH/BD/89140/2012), Francisco Mar tin (SFRH/BD/87488/2012), Inês Moranguinho (SFRH/BD/131062/2017), and Américo Alves (SFRH/BD/128910/2017) were supported by Ph.D. grants from FCT, Portugal.pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHIV-2; antiretroviral activity; integrase inhibitors (INIs); spiro-β-lactam BSS-730A; instantaneous inhibitory potential (IIP); drug resistancept_PT
dc.titleHigh Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patientspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue22pt_PT
oaire.citation.startPage14300pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume23pt_PT
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