DOI: 10.5061/dryad.9w0vt4bqp
title: Data for: Learning from full characterization of HIV proviruses in people receiving Long-Acting Cabotegravir/Rilpivirine with history of replication on the antiretroviral classes

description: To better understand factors associated with virological response, we
 characterized retrospectively HIV proviruses of seven People-With-HIV who
 received long-acting cabotegravir/rilpivirine (CAB/RPV-LA) selected
 according the following criteria: virological control achieved despite a
 history of viral replication on one or both corresponding antiretroviral
 classes (n=6); virological failure (VF) post CAB/RPV-LA initiation (n=1).
 The last available blood samples before the initiation of CAB/RPV-LA were
 analyzed retrospectively. Near full-length HIV-DNA genome haplotypes were
 inferred from Nanopore sequencing using in-vivo Genome-Diversity-Analyzer
 (iGDA) to search for archived Drug Resistance Mutations (DRMs) and to
 evaluate the frequency and the intactness of proviruses harboring DRMs.
 Archived DRMs including G-to-A mutations were found in samples from three
 subjects who maintained virological control. Genomes harboring DRMs were
 majorly in minority variants (&lt;20%) and were defective in all cases
 except for one participant. In this participant, intact genomes with H221Y
 mutation on reverse transcriptase were detected
 representing 11 copies/106 PBMCs. The other mutations observed in the
 participants of the study resulted most likely from hypermutations. The
 subject with VF presented archived mutations, all associated with defects.
 Other factors could explain this VF. Our findings highlight the difficulty
 in interpreting the clinical significance of DRMs when detected in
 proviral DNA and the need to filter out hypermutated sequences. Detected
 DRMs could be harbored by defective archived genomes unlikely to
 contribute to treatment failure.
description: A near full-length HIV genome nanopore single genome sequencing
 (NFG) was performed on HIV DNA after limiting dilution to search for
 archived DRMs, link them with each other, and evaluate the intactness of
 proviruses harboring these DRMs. A de-hosting step was performed using the
 VIRiONT pipeline. A custom-designed bioinformatic pipeline adapted from
 the in-vivo Genome Diversity Analyzer (iGDA) algorithm was developed to
 recover representative haplotypes using the following initial criteria:
 Total reads &gt;30, Min length &gt;1,000 bp, Min freq &gt;0.01
 (1%), Mean depth &gt;100 reads.
description: # Data for: Learning from full characterization of HIV proviruses in
 people receiving Long-Acting Cabotegravir/Rilpivirine with history of
 replication on the antiretroviral classes
 [https://doi.org/10.5061/dryad.9w0vt4bqp](https://doi.org/10.5061/dryad.9w0vt4bqp) A near full-length HIV genome nanopore single genome sequencing (NFG) was performed on HIV DNA after limiting dilution to search for archived DRMs and to evaluate the intactness of proviruses harboring these DRMs in blood samples taken before the switch to CAB/RPV-LA in 7 People-With-HIV-1 (ID1-7). A de-hosting step was performed using the VIRiONT pipeline (1). A custom-designed bioinformatic pipeline adapted from the in-vivo Genome Diversity Analyzer (iGDA) algorithm was developed to recover representative haplotypes (2) using the following initial criteria: Total reads &gt;30, Min length &gt;1,000 bp, Min freq &gt;0.01 (1%), Mean depth &gt;100 reads. 1.       Charre C, Regue H, Dény P, Josset L, Chemin I, Zoulim F, et al. Improved hepatitis delta virus genome characterization by single molecule full-length genome sequencing combined with VIRiONT pipeline. J Med Virol. 2023 Mar;95(3):e28634. 2.       Feng Z, Clemente JC, Wong B, Schadt EE. Detecting and phasing minor single-nucleotide variants from long-read sequencing data. Nat Commun. 2021 May 24;12(1):3032. ## Description of the data and file structure Infered HIV-1 haplotypes from circulating blood samples are uploaded as a fasta file. ID1 to ID7 represent the participants from the study. Each fasta sequence represents one haplotype generated from the Near-full genome sequencing.  For ID7, haplotypes were generated one year after virological failure.