Evaluation of HIV-1 transmitted drug-resistance among subtypes circulating from 2022 to 2024 in Italy: a refined analysis through next-generation sequencing

Abstract

Background: Monitoring HIV-1 subtype circulation and transmitted drug resistance (TDR) remains a key priority, particularly since the rollout of high-sensitivity next-generation sequencing (NGS).

Methods: Routine plasma HIV-1 RNA NGS genotyping data were collected from newly diagnosed individuals in Italy over 2022-24. HIV-1 TDR and genotypic susceptibility were evaluated through HIVdb with NGS set at 10% and 20%. Subtype and transmission clusters (TC) were determined through the maximum likelihood phylogeny based on the GTR + F + R9 model.

Results: Seven hundred and forty-two individuals were included, 51.9% harbouring non-B strains [CRF02_AG (18.1%); CRF BF (6.1%); A1/A3/A6 (7.1%); others (20.5%)]. TDR prevalence to any class was 11.7% at Sanger-like NGS-setting (>20%), slightly increased (15.0%) at 10% NGS-setting, and significantly varied across subtypes, with the highest prevalence observed in B subtype. Most antiretrovirals showed full genotypic activity in nearly 99% of individuals, except for efavirenz and rilpivirine (proportion of individuals with full activity <92%). A total of 57 TC were detected: 40 pairs, 17 clusters (>2 sequences). Thirteen TC (22.8%, 8 pairs, 5 clusters) involved individuals harbouring TDR. TDR was detected as minority mutations in five TC.

Conclusions: A high proportion of HIV-1 non-B subtypes circulate in Italy. TDR prevalence is around 12% using NGS at Sanger-like threshold and moderately increases to 15% when NGS is set at 10%. However, the impact of the detected TDR on the susceptibility to currently used antiretrovirals in clinical practice is negligible.