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Journal of medical virology
Mar, 2025;97 (3): e70317.

Susceptibility to Lenacapavir Among Newly Diagnosed HIV-Positive Patients Followed Up in Mozambique That Presented With Primary Antiretroviral Resistance to Other Classes.

Cruz S Sebasti��o, Jamila Bathy, Tacilta Nhampossa, Andr�� Santos, Mafalda Miranda, Neusa Magode Manhi��a, Rub��o Bila, Delfino Vubil, Sofia Seabra, Maria Ros��rio O Martins, Marta Giovanetti, Perpetua Gomes, Marta Pingarilho, Ana B Abecasis, Victor Pimentel
Author Information
  1. Cruz S Sebasti��o: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal. ORCID
  2. Jamila Bathy: Centro de Investiga����o em Sa��de de Manhi��a (CISM), Manhi��a, Mozambique.
  3. Tacilta Nhampossa: Centro de Investiga����o em Sa��de de Manhi��a (CISM), Manhi��a, Mozambique.
  4. Andr�� Santos: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.
  5. Mafalda Miranda: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.
  6. Neusa Magode Manhi��a: Servi��o Distrital de Sa��de, Mulher e A����o Social (SDSMAS) de Manhi��a, Manhi��a, Mo��ambique.
  7. Rub��o Bila: Servi��o Distrital de Sa��de, Mulher e A����o Social (SDSMAS) de Manhi��a, Manhi��a, Mo��ambique.
  8. Delfino Vubil: Centro de Investiga����o em Sa��de de Manhi��a (CISM), Manhi��a, Mozambique.
  9. Sofia Seabra: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.
  10. Maria Ros��rio O Martins: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.
  11. Marta Giovanetti: Department of Science and Technology for Humans and the Environment, University of Campus Bio-Medico di Roma, Rome, Italy. ORCID
  12. Perpetua Gomes: Laborat��rio de Biologia Molecular (LMCBM, SPC, CHLO-HEM), Lisbon, Portugal.
  13. Marta Pingarilho: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.
  14. Ana B Abecasis: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.
  15. Victor Pimentel: Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal. ORCID
PMID: 40109100 DOI: 10.1002/jmv.70317

Abstract

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.

Keywords

HIV���1 Mozambique drug resistance mutations lenacapavir

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Grants

  1. /This study was funded by FCT-Foundation for Science and Technology (MARVEL project - PTDC/SAU-PUB/4018/2021), GHTM-UID/04413/2020, and LA-REAL-LA/P/0117/2020.

MeSH Term

Humans
HIV Infections
Mozambique
Male
Female
Adult
HIV-1
Anti-HIV Agents
Drug Resistance, Viral
Middle Aged
Mutation
Microbial Sensitivity Tests
Drug Resistance, Multiple, Viral

Chemicals

Anti-HIV Agents
Journal Article

Word Cloud

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