Abstract
Increased access to highly active antiretroviral therapy (HAART) by human immunodeficiency virus postive (HIV+) individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.
Highlights
According to the Joint United Nations Programme on HIV/AIDS, approximately 36.7 million people were living with the human immunodeficiency virus (HIV) worldwide at the end of 2016, making HIV infection a major public health problem [1]
Upon analyzing the HIV antiretroviral resistance profiles of the patients by Next-Generation Sequencing (NGS), our study was able to evidence a high prevalence of drug resistance mutations in this cohort, despite the therapeutic success achieved by their carriers
Patients who had a history of previous virological failure, that underwent a change in the therapeutic regimen due to intolerance or poor adherence, that were classified into clinical and/or immunological AIDS [52] or that were under follow-up at the reference center for less than 12 months were excluded from the analysis
Summary
According to the Joint United Nations Programme on HIV/AIDS, approximately 36.7 million people were living with the human immunodeficiency virus (HIV) worldwide at the end of 2016, making HIV infection a major public health problem [1]. Recent studies using NGS for HIV-1 sequencing were able to detect minority variants below 1% in frequency in the viral population, allowing the identification of drug-resistant minority variants, the study of transmitted resistant viruses and the impact of those minority variants on treatment efficacy [21,22,23,24,25]. We have assessed the presence of HIV minority drug-resistant variants archived in PBMC samples in a Brazilian cohort of chronic HIV patients undergoing HAART as first-line therapy and with undetectable viral load. Upon analyzing the HIV antiretroviral resistance profiles of the patients by NGS, our study was able to evidence a high prevalence of drug resistance mutations in this cohort, despite the therapeutic success achieved by their carriers. This is the first study investigating the presence of HIV minority drug resistance mutations among Brazilian patients under virologic control
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