Publicação
Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes
| Resumo: | Multidrug-resistant HIV patients have limited ART options. Lenacapavir (LEN) is a capsid inhibitor that exhibits substantial antiviral activity in patients with therapeutic failure but is also proposed for PrEP. Herein, we assessed LEN susceptibility among ART-naive HIV patients with drug resistance in Mozambique. In this study, 63 patients with DRM against PIs, NRTIs, NNRTIs, and INSTIs were included. The gag (p24) and env fragments were amplified with a low-cost in-house protocol and sequenced with nanopore. HIVDR database from Stanford University was used to assess LEN resistance and geno2pheno to assess viral tropism and protease/maturation inhibitor-associated mutations. A total of 59 patients were successfully sequenced. About 29% had DRMs to PIs, 5% to NRTI, 83% to NNRTI, and 2% to INSTI. No DRMs to LEN were detected. Additionally, 42% of the sequences presented protease/maturation inhibitor-associated mutations. A relationship was observed between the E138A/G mutation and protease/maturation inhibitors (p = 0.004). We identified changes at the first codon position of position 56 of the p24 gag gene, which represents a key site for resistance to LEN. Also, codon 66 was highly conserved. Our results support the potential effectiveness of lenacapavir as a PrEP regimen or rescue therapy for patients with at least one drug-resistance mutation. |
|---|---|
| Autores principais: | Sebastião, Cruz S. |
| Outros Autores: | Bathy, Jamila; Nhampossa, Tacilta; Santos, André; Miranda, Mafalda; Manhiça, Neusa Magode; Bila, Rubão; Vubil, Delfino; Seabra, Sofia; Martins, Maria Rosário O.; Giovanetti, Marta; Gomes, Perpétua; Pingarilho, Marta; Abecasis, Ana B.; Pimentel, Victor |
| Assunto: | drug resistance mutations HIV-1 lenacapavir Mozambique |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | contribuição para revista |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Egas Moniz - Cooperativa de Ensino Superior, CRL |
| Idioma: | inglês |
| Origem: | Egas Moniz - Cooperativa de Ensino Superior, CRL |
| _version_ | 1866413231759687680 |
|---|---|
| author | Sebastião, Cruz S. |
| author2 | Bathy, Jamila Nhampossa, Tacilta Santos, André Miranda, Mafalda Manhiça, Neusa Magode Bila, Rubão Vubil, Delfino Seabra, Sofia Martins, Maria Rosário O. Giovanetti, Marta Gomes, Perpétua Pingarilho, Marta Abecasis, Ana B. Pimentel, Victor |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Sebastião, Cruz S. Bathy, Jamila Nhampossa, Tacilta Santos, André Miranda, Mafalda Manhiça, Neusa Magode Bila, Rubão Vubil, Delfino Seabra, Sofia Martins, Maria Rosário O. Giovanetti, Marta Gomes, Perpétua Pingarilho, Marta Abecasis, Ana B. Pimentel, Victor |
| author_role | author |
| contributor_name_str_mv | Repositório Comum |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Sebastião, Cruz S.\"},{\"Person.name\":\"Bathy, Jamila\"},{\"Person.name\":\"Nhampossa, Tacilta\"},{\"Person.name\":\"Santos, André\"},{\"Person.name\":\"Miranda, Mafalda\"},{\"Person.name\":\"Manhiça, Neusa Magode\"},{\"Person.name\":\"Bila, Rubão\"},{\"Person.name\":\"Vubil, Delfino\"},{\"Person.name\":\"Seabra, Sofia\"},{\"Person.name\":\"Martins, Maria Rosário O.\"},{\"Person.name\":\"Giovanetti, Marta\"},{\"Person.name\":\"Gomes, Perpétua\"},{\"Person.name\":\"Pingarilho, Marta\"},{\"Person.name\":\"Abecasis, Ana B.\"},{\"Person.name\":\"Pimentel, Victor\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Comum |
| datacite.creators.creator.creatorName.fl_str_mv | Sebastião, Cruz S. Bathy, Jamila Nhampossa, Tacilta Santos, André Miranda, Mafalda Manhiça, Neusa Magode Bila, Rubão Vubil, Delfino Seabra, Sofia Martins, Maria Rosário O. Giovanetti, Marta Gomes, Perpétua Pingarilho, Marta Abecasis, Ana B. Pimentel, Victor |
| datacite.date.Accepted.fl_str_mv | 2025-03-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2026-05-26T14:08:02Z |
| datacite.date.embargoed.fl_str_mv | 2026-05-26T14:08:02Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | drug resistance mutations HIV-1 lenacapavir Mozambique |
| datacite.titles.title.fl_str_mv | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| dc.contributor.none.fl_str_mv | Repositório Comum |
| dc.creator.none.fl_str_mv | Sebastião, Cruz S. Bathy, Jamila Nhampossa, Tacilta Santos, André Miranda, Mafalda Manhiça, Neusa Magode Bila, Rubão Vubil, Delfino Seabra, Sofia Martins, Maria Rosário O. Giovanetti, Marta Gomes, Perpétua Pingarilho, Marta Abecasis, Ana B. Pimentel, Victor |
| dc.date.Accepted.fl_str_mv | 2025-03-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2026-05-26T14:08:02Z |
| dc.date.embargoed.fl_str_mv | 2026-05-26T14:08:02Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.26/63322 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Wiley |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | drug resistance mutations HIV-1 lenacapavir Mozambique |
| dc.title.fl_str_mv | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_3e5a |
| description | Multidrug-resistant HIV patients have limited ART options. Lenacapavir (LEN) is a capsid inhibitor that exhibits substantial antiviral activity in patients with therapeutic failure but is also proposed for PrEP. Herein, we assessed LEN susceptibility among ART-naive HIV patients with drug resistance in Mozambique. In this study, 63 patients with DRM against PIs, NRTIs, NNRTIs, and INSTIs were included. The gag (p24) and env fragments were amplified with a low-cost in-house protocol and sequenced with nanopore. HIVDR database from Stanford University was used to assess LEN resistance and geno2pheno to assess viral tropism and protease/maturation inhibitor-associated mutations. A total of 59 patients were successfully sequenced. About 29% had DRMs to PIs, 5% to NRTI, 83% to NNRTI, and 2% to INSTI. No DRMs to LEN were detected. Additionally, 42% of the sequences presented protease/maturation inhibitor-associated mutations. A relationship was observed between the E138A/G mutation and protease/maturation inhibitors (p = 0.004). We identified changes at the first codon position of position 56 of the p24 gag gene, which represents a key site for resistance to LEN. Also, codon 66 was highly conserved. Our results support the potential effectiveness of lenacapavir as a PrEP regimen or rescue therapy for patients with at least one drug-resistance mutation. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | contributionToPeriodical |
| fulltext.url.fl_str_mv | https://comum.rcaap.pt/bitstreams/bf9a9732-dff4-46ee-8c2e-e24139e44ee8/download |
| id | em_7492e4ed4d5960fe2a7bbcfbfea4c7f1 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.26/63322 |
| instacron_str | em |
| institution | Egas Moniz - Cooperativa de Ensino Superior, CRL |
| instname_str | Egas Moniz - Cooperativa de Ensino Superior, CRL |
| language | eng |
| network_acronym_str | em |
| network_name_str | Egas Moniz - Cooperativa de Ensino Superior, CRL |
| oai_identifier_str | oai:comum.rcaap.pt:10400.26/63322 |
| organization_str_mv | urn:organizationAcronym:em |
| person_str_mv | Sebastião, Cruz S. Bathy, Jamila Nhampossa, Tacilta Santos, André Miranda, Mafalda Manhiça, Neusa Magode Bila, Rubão Vubil, Delfino Seabra, Sofia Martins, Maria Rosário O. Giovanetti, Marta Gomes, Perpétua Pingarilho, Marta Abecasis, Ana B. Pimentel, Victor |
| publishDate | 2025 |
| publisher.none.fl_str_mv | Wiley |
| reponame_str | Egas Moniz - Cooperativa de Ensino Superior, CRL |
| repository_id_str | urn:repositoryAcronym:em |
| service_str_mv | urn:repositoryAcronym:em |
| spelling | engWileyengMultidrug-resistant HIV patients have limited ART options. Lenacapavir (LEN) is a capsid inhibitor that exhibits substantial antiviral activity in patients with therapeutic failure but is also proposed for PrEP. Herein, we assessed LEN susceptibility among ART-naive HIV patients with drug resistance in Mozambique. In this study, 63 patients with DRM against PIs, NRTIs, NNRTIs, and INSTIs were included. The gag (p24) and env fragments were amplified with a low-cost in-house protocol and sequenced with nanopore. HIVDR database from Stanford University was used to assess LEN resistance and geno2pheno to assess viral tropism and protease/maturation inhibitor-associated mutations. A total of 59 patients were successfully sequenced. About 29% had DRMs to PIs, 5% to NRTI, 83% to NNRTI, and 2% to INSTI. No DRMs to LEN were detected. Additionally, 42% of the sequences presented protease/maturation inhibitor-associated mutations. A relationship was observed between the E138A/G mutation and protease/maturation inhibitors (p = 0.004). We identified changes at the first codon position of position 56 of the p24 gag gene, which represents a key site for resistance to LEN. Also, codon 66 was highly conserved. Our results support the potential effectiveness of lenacapavir as a PrEP regimen or rescue therapy for patients with at least one drug-resistance mutation.application/pdfengSusceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classesSebastião, Cruz S.Bathy, JamilaNhampossa, TaciltaSantos, AndréMiranda, MafaldaManhiça, Neusa MagodeBila, RubãoVubil, DelfinoSeabra, SofiaMartins, Maria Rosário O.Giovanetti, MartaGomes, PerpétuaPingarilho, MartaAbecasis, Ana B.Pimentel, VictorHostingInstitutionOrganizationalRepositório Comume-mailmailto:comum@rcaap.ptcomum@rcaap.ptISSNIsPartOf1096-9071DOIIsPartOf10.1002/jmv.703172026-05-26T14:08:02Z2025-032025-03-01T00:00:00ZHandlehttp://hdl.handle.net/10400.26/63322http://purl.org/coar/access_right/c_abf2open accessdrug resistance mutationsHIV-1lenacapavirMozambique484857 bytesother research producthttp://purl.org/coar/resource_type/c_3e5acontribution to journal2025-03http://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://comum.rcaap.pt/bitstreams/bf9a9732-dff4-46ee-8c2e-e24139e44ee8/downloadJournal of Medical Virology973e70317 |
| spellingShingle | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes Sebastião, Cruz S. drug resistance mutations HIV-1 lenacapavir Mozambique |
| status | SINGLETON |
| subject.fl_str_mv | drug resistance mutations HIV-1 lenacapavir Mozambique |
| title | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| title_full | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| title_fullStr | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| title_full_unstemmed | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| title_short | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| title_sort | Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes |
| topic | drug resistance mutations HIV-1 lenacapavir Mozambique |
| topic_facet | drug resistance mutations HIV-1 lenacapavir Mozambique |
| url | http://hdl.handle.net/10400.26/63322 |
| visible | 1 |