☆ 4.7 Article

Viral resistance burden and APOBEC editing correlate with virological response in heavily treatment-experienced people living with multi-drug resistant HIV

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2022)

期刊

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

卷 59, 期 1, 页码 -

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ELSEVIER

DOI: 10.1016/j.ijantimicag.2021.106492

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HIV; Multidrug resistance; Heavily treatment-experienced people; Next-generation sequencing; Mutational load; APOBEC editing

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Infectious Diseases Microbiology Pharmacology & Pharmacy

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ViiV Healthcare
Theratechnologies

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The study found that heavily treatment-experienced individuals with multidrug-resistant HIV had high levels of drug resistance mutational load but less pronounced APOBEC editing. Patients who failed treatment showed higher levels of DNA resistance and mutational load compared to those who responded.

Background: The impact of drug resistance mutational load and APOBEC editing in heavily treatment-experienced (HTE) people living with multidrug-resistant HIV has not been investigated. Material and Methods: This study explored the HIV-DNA and HIV-RNA mutational load of drug resistance and APOBEC-related mutations through next-generation sequencing (NGS, Illumina MiSeq) in 20 failing HTE participants enrolled in the PRESTIGIO registry. Results: The patients showed high levels of both HIV-DNA (4.5 [4.0-5.2] log(10) copies/10(6) T-CD4+ cell) and HIV-RNA (4.5 [4.1-5.0] log(10) copies/mL) with complex resistance patterns in both compartments. Among the 255 drug-resistant mutations found, 66.3% were concordantly detected in both HIV-DNA and HIV-RNA; 71.3% of mutations were already present in historical Sanger genotypes. At an intra-patient frequency > 5%, a considerable proportion of mutations detected through DNA-NGS were found in historical genotypes but not through RNA-NGS, and few patients had APOBEC-related mutations. Of 14 patients who switched therapy, the five who failed treatment had DNA resistance with higher intra-patient frequency and higher DNA/RNA mutational load in a context of tendentially less pronounced APOBEC editing compared with those who responded. Conclusions: Using NGS in HIV-DNA and HIV-RNA together with APOBEC editing evaluation might help to identify HTE individuals with MDR who are more prone to experience virological failure. (C) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

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Sequencing of monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection

Philippe Colson, Gwilherm Penant, Jeremy Delerce, Celine Boschi, Nathalie Wurtz, Marielle Bedotto, Stephanie Branger, Philippe Brouqui, Philippe Parola, Jean-Christophe Lagier, Nadim Cassir, Herve Tissot-Dupont, Matthieu Million, Sarah Aherfi, Bernard La Scola

Summary: A large outbreak of Monkeypox virus (MPXV) infections occurred in nonendemic countries in May 2022. DNA metagenomics using next-generation sequencing was performed on clinical samples from MPXV-infected patients diagnosed between June and July 2022. The study identified 18 MPXV genomes classified in clade IIb, lineage B.1, with four B.1 sublineages. The genomes showed a high number of mutations compared to previous genomes, including nonsynonymous mutations in genes encoding central proteins and the presence of bacterial superinfection in some patients.

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