Frequent detection of CXCR4-using viruses among Brazilian blood donors with HIV-1 long-standing infection and unknown clinical stage: Analysis of massive parallel sequencing data

Abstract

The determination of viral tropism is critically important and highly recommended to guide therapy with the CCR5 antagonist, which does not inhibit the effect of X4-tropic viruses. Here, we report the prevalence of HIV-1×4 HIV strains in 84 proviral DNA massively parallel sequencing “MPS” data from well-defined non-recently infected first-time Brazilian blood donors. The MPS data covering the entire V3 region of the env gene was extracted from our recently generated HIV-1 genomes sequenced by a paired-end protocol (Illumina). Of the 84 MPS data samples, 63 (75%) were derived from donors with long-standing infection and 21 (25%) were lacking stage information. HIV‐1 tropism was inferred using Geno2pheno (g2p) [454] algorithm (FPR=1%, 2.5%, and 3.75%). Among the 84 data samples for which tropism was defined by g2p2.5%, 13 (15.5%) participants had detectable CXCR4-using viruses in their MPS reads. Mixed infections with R5 and X4 were observed in 11.9% of the study subjects and minority X4 viruses were detected in 7 (8.3%) of participants. Nine of the 63 (14.3%) subjects with LS infection were predicted by g2p 2.5% to harbor proviral CXCR4-using viruses. Our findings of a high proportion of blood donors (15.5%) harboring CXCR4-using viruses in PBMCs may indicate that this phenomenon is common. These findings may have implications for clinical and therapeutic aspects and may benefit individuals who plan to receive CCR5 antagonists.