HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China
Open Access
- 25 February 2021
- Vol. 10 (3), 264
- https://doi.org/10.3390/pathogens10030264
Abstract
Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.Keywords
Funding Information
- National Natural Science Foundation of China (11971479)
- Ministry of Science and Technology of China (2017ZX10201101, 2018ZX10721102-006, AB16380213)
This publication has 48 references indexed in Scilit:
- Factors associated with attrition, mortality, and loss to follow up after antiretroviral therapy initiation: data from an HIV cohort study in IndiaGlobal Health Action, 2013
- Incidence and Associated Factors of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving Antiretroviral TreatmentPLOS ONE, 2013
- Attrition among Human Immunodeficiency Virus (HIV)- Infected Patients Initiating Antiretroviral Therapy in China, 2003–2010PLOS ONE, 2012
- Lopinavir/ritonavir single agent therapy as a universal combination antiretroviral therapy stopping strategy: results from the STOP 1 and STOP 2 studiesJournal of Antimicrobial Chemotherapy, 2011
- Prevalence of Low-Level HIV-1 Variants with Reverse Transcriptase Mutation K65R and the Effect of Antiretroviral Drug Exposure on Variant LevelsAntiviral Therapy, 2011
- Nonstructured Treatment Interruptions Among Injection Drug Users in Baltimore, MDJAIDS Journal of Acquired Immune Deficiency Syndromes, 2009
- In Vivo Fitness Cost of the M184V Mutation in Multidrug-Resistant Human Immunodeficiency Virus Type 1 in the Absence of LamivudineJournal of Virology, 2009
- Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or deathHIV Medicine, 2007
- CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trialThe Lancet, 2006
- Web Resources for HIV Type 1 Genotypic-Resistance Test InterpretationClinical Infectious Diseases, 2006