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

Armenia, Daniele; Santoro, Maria Mercedes; Bellocchi, Maria Concetta; Carioti, Luca; Galli, Laura; Galli, Andrea; Scutari, Rossana; Salsi, Eleonora; Mussini, Cristina; Sterrantino, Gaetana; Calza, Leonardo; Rossetti, Barbara; Zazzi, Maurizio; Castagna, Antonella

doi:10.1016/j.ijantimicag.2021.106492

Cited by 7 publications

(3 citation statements)

References 45 publications

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“…Finally, the role of NGS in genotypic drug resistance testing has been explored. Armenia et al used NGS to evaluate HIV-DNA and HIV-RNA mutational loads of drug resistance and apolipoprotein B messenger RNA editing enzyme catalytic polypeptide (APOBEC)-related mutations in 20 virologically failing individuals enrolled in the PRESTIGIO Registry 38. The study concluded that using NGS in HIV-DNA and HIV-RNA together with measurement of APOBEC editing might help identify HTE individuals with multidrug resistance who are more prone to experience virological failure.…”

Section: Cohort Descriptionmentioning

confidence: 99%

“…Armenia et al used NGS to evaluate HIV-DNA and HIV-RNA mutational loads of drug resistance and apolipoprotein B messenger RNA editing enzyme catalytic polypeptide (APOBEC)-related mutations in 20 virologically failing individuals enrolled in the PRESTIGIO Registry. 38 The study concluded that using NGS in HIV-DNA and HIV-RNA together with measurement of APOBEC editing might help identify HTE individuals with multidrug resistance who are more prone to experience virological failure. Furthermore, in a recently published case of an HTE woman from the PRESTIGIO Registry, RNA-based NGS, performed at virological failure, was used to exclude the presence of minority resistance-associated mutations and, together with available prior genotypic resistance tests, clinical history and adherence issues, to select an effective antiretroviral regimen with a low pill burden.…”

Section: Cohort Descriptionmentioning

confidence: 99%

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Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors

Clemente,

Galli,

Lolatto

et al. 2024

BMJ Open

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PurposeThe PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population.ParticipantsThe PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry.Findings to dateThe open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples.Future plansThe registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole.Trial registration numberNCT04098315.

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Section: Cohort Descriptionmentioning

confidence: 99%

Section: Cohort Descriptionmentioning

confidence: 99%

Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors

Clemente,

Galli,

Lolatto

et al. 2024

BMJ Open

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“…The new capsid and maturation antiretroviral (ARV) treatments have improved patient prognosis [ 11 , 12 ]. However, virological failure of the new ARV has been reported [ 13 , 14 , 15 , 16 , 17 ]. Several HIVDR interpretation algorithms have been widely used for assessing virological response in retrospective analyses: ANRS [ 18 ], Stanford HIVdb [ 19 ], and IAS-USA [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

From Capillary Electrophoresis to Deep Sequencing: An Improved HIV-1 Drug Resistance Assessment Solution Using In Vitro Diagnostic (IVD) Assays and Software

Mohamed¹,

Boulmé²,

Sayada

2023

Viruses

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Background: Drug-resistance mutations were mostly detected using capillary electrophoresis sequencing, which does not detect minor variants with a frequency below 20%. Next-Generation Sequencing (NGS) can now detect additional mutations which can be useful for HIV-1 drug resistance interpretation. The objective of this study was to evaluate the performances of CE-IVD assays for HIV-1 drug-resistance assessment both for target-specific and whole-genome sequencing, using standardized end-to-end solution platforms. Methods: A total of 301 clinical samples were prepared, extracted, and amplified for the three HIV-1 genomic targets, Protease (PR), Reverse Transcriptase (RT), and Integrase (INT), using the CE-IVD DeepChek® Assays; and then 19 clinical samples, using the CE-IVD DeepChek® HIV Whole Genome Assay, were sequenced on the NGS iSeq100 and MiSeq (Illumina). Sequences were compared to those obtained by capillary electrophoresis. Quality control for Molecular Diagnostics (QCMD) samples was added to validate the clinical accuracy of these in vitro diagnostics (IVDs). Nineteen clinical samples were then tested with the same sample collection, handling, and measurement procedure for evaluating the use of NGS for whole-genome HIV-1. Sequencing analyzer outputs were submitted to a downstream CE-IVD standalone software tailored for HIV-1 analysis and interpretation. Results: The limits of range detection were 1000 to 106 cp/mL for the HIV-1 target-specific sequencing. The median coverage per sample for the three amplicons (PR/RT and INT) was 13,237 reads. High analytical reproducibility and repeatability were evidenced by a positive percent agreement of 100%. Duplicated samples in two distinct NGS runs were 100% homologous. NGS detected all the mutations found by capillary electrophoresis and identified additional resistance variants. A perfect accuracy score with the QCMD panel detection of drug-resistance mutations was obtained. Conclusions: This study is the first evaluation of the DeepChek® Assays for targets specific (PR/RT and INT) and whole genome. A cutoff of 3% allowed for a better characterization of the viral population by identifying additional resistance mutations and improving the HIV-1 drug-resistance interpretation. The use of whole-genome sequencing is an additional and complementary tool to detect mutations in newly infected untreated patients and heavily experienced patients, both with higher HIV-1 viral-load profiles, to offer new insight and treatment strategies, especially using the new HIV-1 capsid/maturation inhibitors and to assess the potential clinical impact of mutations in the HIV-1 genome outside of the usual HIV-1 targets (RT/PR and INT).

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Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry

Saladini

Giammarino

Maggiolo

et al. 2023

International Journal of Antimicrobial Agents

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

Cited by 7 publications

References 45 publications

Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors

Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors

From Capillary Electrophoresis to Deep Sequencing: An Improved HIV-1 Drug Resistance Assessment Solution Using In Vitro Diagnostic (IVD) Assays and Software

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry

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