High level of archived and circulating HIV-1 drug resistance mutations in adolescents with a detectable viremia in Cameroon

Abstract

OBJECTIVE: We previously reported a high prevalence of HIV drug resistance mutations (DRMs) among adolescents with a viral load (VL) ≥ 200 copies/mL. In this study, we complement this analysis by simultaneously characterizing circulating and archived viruses in order to obtain a more comprehensive drug resistance profile. METHODS: Using 127 plasma and paired buffy-coat samples collected between February and September 2021 from 90 adolescents (10-19 years) with a VL ≥ 200 copies/mL, we performed genotyping resistance testing on both circulating and archived viral strains using an in-house Sanger method targeting the reverse transcriptase, protease and integrase genes. The Stanford HIValg programme was used to identify relevant DRMs. RESULTS: We generated 97 (76.4%) paired archived and circulating viral sequences, of which 60 (61.9%) were recombinant CRF02_AG. Globally, about 8/10 participants harboured DRMs to at least one drug class in circulant (80.4%) and archived (77.3%) viruses, slightly higher in samples with VL between 200 and 999 copies/mL and mainly NRTIs and NNRTI-associated resistance. One-third of the participants had cross-resistance to the newer NNRTIs rilpivirine and doravirine, which are not yet available in our settings. More than half (56.7%) of the DRMs were detected in both viral populations, but 2-fold more DRMs were found exclusively in circulant strains (29.8% versus 13.4% in archived viruses). CONCLUSION: The high level of resistance found in this study, coupled with the identification of DRMs either in circulating and archived viruses, only suggests that a comprehensive profiling of DRMs in both viral populations would provide additional information for adolescents with a detectable viremia.