High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients

BackgroundThe development of human immunodeficiency virus (HIV) drug resistance significantly impairs patients’ quality of life. However, the HIV-1 drug resistance patterns in the central nervous system (CNS) have been poorly studied.ObjectiveWe aimed to compare HIV-1 genotypes and drug resistance m...

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Main Authors: Xizi Deng, Jiaojiao Li, Ruiying He, Yingfen Wen, Yaqing Lin, Liya Li, Xuemei Ling, Fengyu Hu, Linghua Li, Yun Lan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1518225/full
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author Xizi Deng
Jiaojiao Li
Ruiying He
Yingfen Wen
Yaqing Lin
Liya Li
Xuemei Ling
Fengyu Hu
Linghua Li
Yun Lan
author_facet Xizi Deng
Jiaojiao Li
Ruiying He
Yingfen Wen
Yaqing Lin
Liya Li
Xuemei Ling
Fengyu Hu
Linghua Li
Yun Lan
author_sort Xizi Deng
collection DOAJ
description BackgroundThe development of human immunodeficiency virus (HIV) drug resistance significantly impairs patients’ quality of life. However, the HIV-1 drug resistance patterns in the central nervous system (CNS) have been poorly studied.ObjectiveWe aimed to compare HIV-1 genotypes and drug resistance mutations (DRMs) derived from the cerebrospinal fluid (CSF) and plasma of antiretroviral therapy (ART)-naive or -experienced patients.MethodsThe matched CSF and plasma samples from 59 patients with HIV were subjected to HIV proteinase (PR), reverse transcriptase (RT), and integrase (IN) gene sequencing. To determine the HIV-1 genotypes, sequences were assessed with the Context-based Modelling for Expeditious Typing (COMET) tool, and the neighbour-joining (NJ) phylogenetic tree was used to confirm the results. Quality control based on genotype and phylogenetic tree analysis was conducted to assess potential sequence contamination during the detection process. The HIV-1 drug resistance database of Stanford University was used to identify DRMs and sensitivity to four drug classes [protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs)].ResultsOf the 59 patients with HIV with matched CSF and plasma samples, samples from 37 were included in the study after excluding the samples that failed to be successfully amplified. CRF01_AE was the most frequently occurring genotype, with a frequency of 46.0% (17/37), followed by CRF07_BC (27.0%, 10/37) and CRF55_01B (10.8%, 4/37). Among the 37 patients, 37.8% (14/37) carried at least one DRM, and the mutation sites were consistent in both CSF and matched plasma, except one. NNRTI-related resistance mutations were the predominant DRMs, particularly V179D/E, present in 71.4% (10/14) of patients with DRM sites, primarily in ART-naive patients.ConclusionA high concordance of HIV-1 DRMs between CSF and plasma samples was observed. No unique mutations were identified in CSF other than those in plasma, indicating that the mutant variants in CSF were derived from blood.
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series Frontiers in Microbiology
spelling doaj-art-cc5ebe73f11b42a9a8c4ff4b0964fe7d2025-08-20T02:40:48ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-03-011610.3389/fmicb.2025.15182251518225High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patientsXizi Deng0Jiaojiao Li1Ruiying He2Yingfen Wen3Yaqing Lin4Liya Li5Xuemei Ling6Fengyu Hu7Linghua Li8Yun Lan9Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Institute of Clinical Infectious Diseases, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Institute of Clinical Infectious Diseases, Guangzhou Medical University, Guangzhou, ChinaInstitute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaBackgroundThe development of human immunodeficiency virus (HIV) drug resistance significantly impairs patients’ quality of life. However, the HIV-1 drug resistance patterns in the central nervous system (CNS) have been poorly studied.ObjectiveWe aimed to compare HIV-1 genotypes and drug resistance mutations (DRMs) derived from the cerebrospinal fluid (CSF) and plasma of antiretroviral therapy (ART)-naive or -experienced patients.MethodsThe matched CSF and plasma samples from 59 patients with HIV were subjected to HIV proteinase (PR), reverse transcriptase (RT), and integrase (IN) gene sequencing. To determine the HIV-1 genotypes, sequences were assessed with the Context-based Modelling for Expeditious Typing (COMET) tool, and the neighbour-joining (NJ) phylogenetic tree was used to confirm the results. Quality control based on genotype and phylogenetic tree analysis was conducted to assess potential sequence contamination during the detection process. The HIV-1 drug resistance database of Stanford University was used to identify DRMs and sensitivity to four drug classes [protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs)].ResultsOf the 59 patients with HIV with matched CSF and plasma samples, samples from 37 were included in the study after excluding the samples that failed to be successfully amplified. CRF01_AE was the most frequently occurring genotype, with a frequency of 46.0% (17/37), followed by CRF07_BC (27.0%, 10/37) and CRF55_01B (10.8%, 4/37). Among the 37 patients, 37.8% (14/37) carried at least one DRM, and the mutation sites were consistent in both CSF and matched plasma, except one. NNRTI-related resistance mutations were the predominant DRMs, particularly V179D/E, present in 71.4% (10/14) of patients with DRM sites, primarily in ART-naive patients.ConclusionA high concordance of HIV-1 DRMs between CSF and plasma samples was observed. No unique mutations were identified in CSF other than those in plasma, indicating that the mutant variants in CSF were derived from blood.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1518225/fullHIV-1CSFplasmadrug resistancegenotype
spellingShingle Xizi Deng
Jiaojiao Li
Ruiying He
Yingfen Wen
Yaqing Lin
Liya Li
Xuemei Ling
Fengyu Hu
Linghua Li
Yun Lan
High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients
Frontiers in Microbiology
HIV-1
CSF
plasma
drug resistance
genotype
title High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients
title_full High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients
title_fullStr High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients
title_full_unstemmed High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients
title_short High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients
title_sort high concordance of human immunodeficiency virus 1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy naive or experienced patients
topic HIV-1
CSF
plasma
drug resistance
genotype
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1518225/full
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