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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

2022-11Contribution to journal Open access
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datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorBártolo, Inês
dc.contributor.authorMoranguinho, Inês
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, Fátima
dc.contributor.authorAlves, Américo J. S.
dc.contributor.authorAlves, Nuno
dc.contributor.authorCaixas, Umbelina
dc.contributor.authorPinto, Inês V.
dc.contributor.authorBarahona, Isabel
dc.contributor.authorMelo, Teresa M. V. D. Pinho e
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2025-11-13T16:17:27Z
dc.date.available2025-11-13T16:17:27Z
dc.date.issued2022-11
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 raltegravir and 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.eng
dc.identifier.citationBártolo I, Moranguinho I, Gonçalves P, Diniz AR, Borrego P, Martin F, Figueiredo I, Gomes P, Gonçalves F, Alves AJS, 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. International Journal of Molecular Sciences. 2022; 23(22):14300. https://doi.org/10.3390/ijms232214300
dc.identifier.doi10.3390/ijms232214300
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/10400.26/59742
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relation.hasversionhttps://doi.org/10.3390/ijms232214300
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHIV-2
dc.subjectantiretroviral activity
dc.subjectintegrase inhibitors (INIs)
dc.subjectspiro-β-lactam BSS-730A
dc.subjectinstantaneous inhibitory potential (IIP)
dc.subjectdrug resistance
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 patientseng
dc.typecontribution to journal
dspace.entity.typePublication
oaire.citation.issue22
oaire.citation.startPage14300
oaire.citation.titleInternational Journal of Molecular Sciences
oaire.citation.volume23
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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