{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:25:13Z","timestamp":1762075513792,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["UIDB\/00313\/2020","UIDP\/QUI\/00313\/2020","UIDB\/04138\/2020","UIDP\/04138\/2020","Norma Transit\u00f3ria\u2013DL57\/2016\/CP1376\/CT0012","SFRH\/BD\/89140\/2012","SFRH\/BD\/87488\/2012","SFRH\/BD\/131062\/2017","SFRH\/BD\/128910\/2017","332821690"],"award-info":[{"award-number":["UIDB\/00313\/2020","UIDP\/QUI\/00313\/2020","UIDB\/04138\/2020","UIDP\/04138\/2020","Norma Transit\u00f3ria\u2013DL57\/2016\/CP1376\/CT0012","SFRH\/BD\/89140\/2012","SFRH\/BD\/87488\/2012","SFRH\/BD\/131062\/2017","SFRH\/BD\/128910\/2017","332821690"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Aga Khan Development Network","award":["UIDB\/00313\/2020","UIDP\/QUI\/00313\/2020","UIDB\/04138\/2020","UIDP\/04138\/2020","Norma Transit\u00f3ria\u2013DL57\/2016\/CP1376\/CT0012","SFRH\/BD\/89140\/2012","SFRH\/BD\/87488\/2012","SFRH\/BD\/131062\/2017","SFRH\/BD\/128910\/2017","332821690"],"award-info":[{"award-number":["UIDB\/00313\/2020","UIDP\/QUI\/00313\/2020","UIDB\/04138\/2020","UIDP\/04138\/2020","Norma Transit\u00f3ria\u2013DL57\/2016\/CP1376\/CT0012","SFRH\/BD\/89140\/2012","SFRH\/BD\/87488\/2012","SFRH\/BD\/131062\/2017","SFRH\/BD\/128910\/2017","332821690"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Integrase 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-na\u00efve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-\u03b2-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-na\u00efve 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-na\u00efve 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.<\/jats:p>","DOI":"10.3390\/ijms232214300","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T06:02:29Z","timestamp":1668751349000},"page":"14300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-\u03b2-Lactam BSS-730A for HIV-2 Isolates from RAL-Na\u00efve and RAL-Failing Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2022-8921","authenticated-orcid":false,"given":"In\u00eas","family":"B\u00e1rtolo","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-0670","authenticated-orcid":false,"given":"In\u00eas","family":"Moranguinho","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-6715","authenticated-orcid":false,"given":"Paloma","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz (CiiEM), Instituto Superior de Ci\u00eancias da Sa\u00fade Egas Moniz, 2829-511 Caparica, Portugal"}]},{"given":"Ana Rita","family":"Diniz","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"}]},{"given":"Pedro","family":"Borrego","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"},{"name":"Centro de Administra\u00e7\u00e3o e Pol\u00edticas P\u00fablicas (CAPP), Instituto Superior de Ci\u00eancias Sociais e Pol\u00edticas (ISCSP), Universidade de Lisboa, 1649-019 Lisboa, Portugal"}]},{"given":"Francisco","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"}]},{"given":"In\u00eas","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"}]},{"given":"Perp\u00e9tua","family":"Gomes","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz (CiiEM), Instituto Superior de Ci\u00eancias da Sa\u00fade Egas Moniz, 2829-511 Caparica, Portugal"},{"name":"Laborat\u00f3rio de Biologia Molecular, LMCBM, SPC, Centro Hospitalar Lisboa Ocidental\u2013HEM, 1649-019 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-5811","authenticated-orcid":false,"given":"F\u00e1tima","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, LMCBM, SPC, Centro Hospitalar Lisboa Ocidental\u2013HEM, 1649-019 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-8796","authenticated-orcid":false,"given":"Am\u00e9rico J. S.","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"given":"Nuno","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"given":"Umbelina","family":"Caixas","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Medicina 1.4, Hospital de S. Jos\u00e9, CHLC, EPE, and Faculdade de Ci\u00eancias M\u00e9dicas, FCM-Nova, Centro de Estudos de Doen\u00e7as Cr\u00f3nicas\u2013CEDOC, 1649-019 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6281-8591","authenticated-orcid":false,"given":"In\u00eas V.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Medicina Interna, Hospital de Cascais Dr. Jos\u00e9 de Almeida, 2755-009 Alcabideche, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2654-0983","authenticated-orcid":false,"given":"Isabel","family":"Barahona","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz (CiiEM), Instituto Superior de Ci\u00eancias da Sa\u00fade Egas Moniz, 2829-511 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-4954","authenticated-orcid":false,"given":"Teresa M. V. D.","family":"Pinho e Melo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-5585","authenticated-orcid":false,"given":"Nuno","family":"Taveira","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-019 Lisboa, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz (CiiEM), Instituto Superior de Ci\u00eancias da Sa\u00fade Egas Moniz, 2829-511 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1099\/vir.0.038638-0","article-title":"Phylogeographical footprint of colonial history in the global dispersal of human immunodeficiency virus type 2 group A","volume":"93","author":"Faria","year":"2012","journal-title":"J. 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