Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan

Weng, Ya-Wei; Chen, I-Tzu; Tsai, Hung-Chin; Wu, Kuan-Sheng; Tseng, Yu‐Ting; Sy, Cheng Len; Chen, Jui-Kuang; Lee, Susan Shin-Jung; Chen, Yao-Shen

doi:10.1186/s12879-019-4389-1

Cited by 16 publications

(12 citation statements)

References 34 publications

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“…Resistance against RTIs and PIs has frequently been determined in HIV patients. [1][2][3][4][5] Attention to TDRM to INSTIs has gradually claimed increased interest after the widespread application of INSTIs. INSTIs are recommended as the first-line treatment regimens for HIV-1 patients, due to their high efficacy and good tolerability, 6,7 and have been increasingly used in treatment-naïve patients with HIV since their introduction in China in 2009.…”

Section: Introductionmentioning

confidence: 99%

Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naïve HIV Patients in Southeast China

Lai¹,

Liu²,

Han³

et al. 2021

DDDT

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Background With the widespread use of integrase strand transfer inhibitors (INSTIs) in the clinical setting, transmission of INSTIs-resistance mutations may increase. Data regarding transmitted drug resistance mutations (TDRM) to INSTIs in Chinese HIV patients are limited. The aim of this study was to summarize the INSTIs TDRM, including the frequency of protease inhibitors (PIs) and reverse transcriptase (RT) inhibitors (RTIs) mutations in treatment-naïve patients in Southeast China. Methods HIV-1 positive patients were retrospectively selected between April 2018 and October 2020 from the Mengchao Hepatobiliary Hospital of Fujian Medical University, the largest designated HIV/AIDS care hospital in Southeast China. Individuals who were antiretroviral therapy-naïve and received antiretroviral drug resistance testing at baseline were included. Clinical data including demographic data, CD4 counts, HIV-RNA loads, and drug resistance mutations were collected. Results A total of 147 patients were enrolled. INSTIs TDRM was rare, with only one primary integrase mutation E138K observed in one sample and one secondary mutation E157Q detected in another sample. The overall prevalence of INSTIs TDRM was 1.36%. A substantial proportion of patients harbored common INSTIs-associated polymorphic variants. Two samples harbored the T215S, M184V and K70E mutations related to nucleoside RTIs (NRTIs). Twelve patients carried nonnucleoside RTIs (NNRTIs)-resistance mutations. Two individuals harbored PIs-resistance mutations: Q58E in one patient and M46I, I54V, V82A, L10F, and Q58E mutations in another patient. The total TDRM rate for RTIs and PIs was 10.20% (15/147), but only 0.68% (1/147) was according to the WHO recommendations on TDRM. Conclusion The rate of INSTIs TDRM was low among therapy-naïve HIV patients in Southeast China. INSTIs as a first-line regimen are suitable for untreated HIV-1 patients in Southeast China. But special attention must be still paid to INSTIs TDRM in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naïve HIV Patients in Southeast China

Lai¹,

Liu²,

Han³

et al. 2021

DDDT

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“…The number of antiretroviral (ARV) available for treatment of HIV infection has increased considerably in recent years; with the onset of highly active ART (HAART) in 1996, the life expectancy of HIV-positive people increased considerably [2,3]. However, the effectiveness of an ARV treatment scheme against virus replication depends on the effectiveness of each ARV and the number of genetic variations of HIV-1 that are required for the expression of virus resistance to ARV [4][5][6]. The increase in treatment failure due to the resistance of the virus to ARVs has been decreasing the number of highly active ARVs available to control the disease [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, the effectiveness of an ARV treatment scheme against virus replication depends on the effectiveness of each ARV and the number of genetic variations of HIV-1 that are required for the expression of virus resistance to ARV [4][5][6]. The increase in treatment failure due to the resistance of the virus to ARVs has been decreasing the number of highly active ARVs available to control the disease [6]. This decrease in effectiveness of ARVs has led to the search for new therapies that help control virus replication and disease progression, an alternative potential is the use of miRNAs [7].…”

Section: Introductionmentioning

confidence: 99%

Plasma microRNA expression levels in HIV-1-positive patients receiving antiretroviral therapy

et al. 2020

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MicroRNAs (miRNAs/miRs) may serve as therapeutic agents or targets in diseases in which the expression of proteins plays an important role. The aim of the present study was to compare the expression levels of specific miRNAs, as well as their correlation with markers of response to antiretroviral (ARV) therapy, in patients with human immunodeficiency virus type 1 (HIV-1) infection with and without resistance to highly active antiretroviral therapy (HAART). Methods: miRNA assays were performed on plasma samples obtained from 20 HIV-1-positive patients. A total of ten patients were divided into two groups: HAART-responsive and HAART-resistant (n=5 per group). Commercial arrays were subsequently used to identify 84 miRNAs. A total of three differentially expressed miRNAs were selected and analyzed by quantitative PCR (qPCR). Five other patients were subsequently added to each group for a new relative expression analysis. The absolute expression level of the two miRNAs was obtained and compared using the Student’s t test. Receiver operating characteristic (ROC) curves were used to identify patients with antiretroviral therapy (ART) resistance. Results: The array analysis revealed that miR-15b-5p, miR-16-5p, miR-20a-5p, miR-26a-5p, miR-126-3p and miR-150-5p were down-regulated in patients with HAART-resistance comparing with HAART-responsive. The expression levels of miR-16-5p, miR-26a-5p and miR-150-5p were confirmed using qPCR. The area under the ROC curve was 1.0 for the three miRNAs. Conclusions: The lower expression levels of miR-16-5p and miR-26a-5p in patients with HAART-resistance suggested that these may serve as potential biomarkers for the identification of HAART-responsive patients.

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“…2,3 The prevalence rate of transmitted drug resistance (TDR) in Taiwan, where routine genotypic drug-resistance testing is not available, is about 10% for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). 4,5 Treatment with the first integrase strand transfer inhibitor (INSTI), raltegravir, combined with two NRTIs was introduced for HIV-1-infected treatment-naïve patients in 2012. Abacavir/dolutegravir/lamivudine (Triumeq) was introduced as the first INSTI-based single-tablet regimen in June 2016, and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya) as the second INSTI-based single-tablet regimen in 2017.…”

Section: Introductionmentioning

confidence: 99%

<p>Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naïve Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan</p>

Tsai¹,

Chen²,

Lee³

et al. 2020

IDR

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Purpose Integrase strand transfer inhibitors (INSTIs) are used as first-line therapy for HIV-1-infected patients. Next-generation sequencing (NGS) can detect low-frequency mutants; however, the clinical value of NGS to detect resistance variants is unknown. This study aimed to evaluate the prevalence of INSTI resistance in southern Taiwan and determine the clinical implications of using NGS to detect integrase region low-level resistant variants. Patients and Methods This retrospective cohort study included antiretroviral therapy-naïve HIV-1-infected individuals at Kaohsiung Veterans General Hospital, Taiwan, from 2013 to 2017. Drug-resistance mutations were determined, and an in-house polymerase chain reaction was used for genotyping INSTI resistance. NGS was used to assess INSTI resistance (≧1%), and the results were compared with those from population sequencing. Drug resistance-associated mutations were defined according to the 2019 IAS-USA HIV drug resistance-associated mutations list, and accessory mutations by a Stanford HIVdb score ≥10 to at least one INSTI. Results A total of 224 patients were included. Subtype B HIV-1 strains were found in 96% of the individuals and subtype CRF01_AE in 4%. The prevalence rates for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and INSTI resistance were 4%, 5.8%, 0.4% and 0.9%, respectively. The most common INSTI resistance-associated mutations were G163K (0.4%) and E138A (0.4%). Of the 38 patients diagnosed in 2017 who had both NGS and population sequencing data, none had INSTI resistance-associated mutations by population sequencing; however, NGS detected four more INSTI resistance-associated mutations with low frequencies (G163R 3.25%, S153F 3.21%, S153Y 1.36% and Y143H 2.06%). Two patients with S153F and S153Y low frequencies mutations started INSTI-based highly active antiretroviral therapy, and none had virological failure by week 48. Conclusion Our findings showed a low rate of HIV drug resistance to INSTIs (0.9%) in treatment-naïve patients. NGS detected more INSTI resistance-associated mutations at a low frequency. Low-level drug resistance-associated mutations to INSTIs identified by NGS did not have an impact on the treatment response to INSTI-based first-line therapy.

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Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan

Cited by 16 publications

References 34 publications

Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naïve HIV Patients in Southeast China

Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naïve HIV Patients in Southeast China

Plasma microRNA expression levels in HIV-1-positive patients receiving antiretroviral therapy

<p>Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naïve Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan</p>

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