Percorrer por autor "Bathy, Jamila"
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- MARVEL-minimising the emergence and dissemination of HIV-1 drug resistance in Portuguese-speaking African Countries (PALOP) : low-cost portable NGS platform for HIV-1 surveillance in AfricaPublication . Sebastião, Cruz S.; Pingarilho, Marta; Bathy, Jamila; Bonfim, Elizângela; Toancha, Katia; Miranda, Mafalda N. S.; Martins, M. Rosário O.; Gomes, Perpétua; Lázaro, Lazismino; Pina-Araujo, Isabel; Nhampossa, Tacilta; Leal, Silvania; Abecasis, Ana B.; Pimentel, VictorBackground: HIV-1 infections remain a global public health concern. Scaled-up antiretroviral treatment (ART) is crucial for reducing morbidity and mortality related to HIV/AIDS. The emergence of drug-resistance mutations (DRMs) compromises viral suppression and contributes to the continued HIV-1 transmission. Several reports indicate a recent increase in acquired (ADR) and transmitted (TDR) drug resistance in Africa, probably linked to the lack of implementation of HIV drug resistance (HIVDR) testing and suboptimal treatment adherence. Herein, we will develop a low-cost protocol using third-generation sequencing (Oxford Nanopore Technology) for HIV-1 surveillance in Portuguese-speaking African Countries - PALOP [Angola (AO), Cape Verde (CV), Mozambique (MZ), and Sao Tome & Principe (STP)]. Methods: This is a multicentric cross-sectional study that includes around 600 adult patients newly diagnosed with HIV-1 in the PALOP. An epidemiological questionnaire previously validated by our research team will be used to collect sociodemographic and clinical data. Also, whole blood samples will be collected and the plasma samples will be subjected to drug resistance testing using an in-house low-cost NGS protocol. Data analysis will involve bioinformatics, biostatistics and machine learning techniques to generate accurate and up-to-date information about HIV-1 genetic diversity, ADR and TDR. Discussion: The implementation of this low-cost NGS platform for HIV-1 surveillance in the PALOP will allow: (i) to increase DRM surveillance capacity in resource-limited settings; (ii) to understand the pattern and determinants of dissemination of resistant HIV-1 strains; and (iii) to promote the development of technical and scientific skills of African researchers for genomic surveillance of viral pathogens and bioinformatics analysis. These objectives will contribute to reinforcing the capacity to combat HIV infection in Africa by optimizing the selection of ART regimens, improving viral suppression, and reducing ADR or TDR prevalence in PALOPs, with relevant implications for public health.
- Susceptibility to lenacapavir among newly diagnosed HIV-positive patients followed up in Mozambique that presented with primary antiretroviral resistance to other classesPublication . 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, VictorMultidrug-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.