Data for: Learning from full characterization of HIV proviruses in people receiving Long-Acting Cabotegravir/Rilpivirine with history of replication on the antiretroviral classes

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 (<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.