Publicação

Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classes

Detalhes bibliográficos
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

Descrição
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.