Interest and performances of HIV whole genome next‐generation sequencing in a diagnosis laboratory

Background HIV-1 drug resistance monitoring traditionally relies on Sanger sequencing of targeted pol regions. Whole genome sequencing (WGS) enables the detection of mutations in all coding regions, including minority variants and resistance-associated polymorphisms outside pol, which may impact treatment with novel antiretrovirals. Objectives To evaluate the clinical performance of a CE-IVD certified HIV-1 WGS kit (DeepChek®, ABL SA) in a routine diagnostic laboratory, and to compare its results with those obtained by a target-specific sequencing assay. Study Design We retrospectively analyzed 20 HIV-1 RNA/DNA samples from six individuals infected with different subtypes (A1-like, B, CRF-02, G, H) and followed at Caen University Hospital between 2018–2022. HIV-1 WGS was performed in five overlapping fragments using the DeepChek® Whole Genome HIV-1 Genotyping kit and sequenced on an Illumina iSeq100 platform. Results were compared to previous genotypes obtained by a CE-IVD target-specific kit. Results WGS achieved complete genome coverage for 18/20 samples, with subtype assignments consistent with patient history. The assay detected both majority (≥20%) and minority (3–20%) resistance mutations, including gp120 S375T and M434I associated with Fostemsavir resistance. Concordance with target-specific sequencing was high for pol regions, with WGS providing additional data on env and gag polymorphisms. Conclusions HIV-1 WGS is feasible in a hospital diagnostic laboratory and provides comprehensive resistance profiling, including detection of minority variants and novel target site polymorphisms. Its implementation can enhance therapeutic decision-making in the context of evolving antiretroviral landscapes.