Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

Sun, Zesong; Ouyang, Jian; Zhao, Bin; An, Minghui; Wang, Lin; Ding, Haibo; Han, Xiaoxu

doi:10.1186/s12879-020-4808-3

Cited by 6 publications

(3 citation statements)

References 38 publications

(52 reference statements)

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“…3 Nevertheless, treatment outcomes were largely unaffected by the large number of natural polymorphisms found in CRF01_AE. 9 Based on the present results, CRF01_AE was identified as the dominant HIV-1 CRF in Makasar, Indonesia, similar to other regions in Indonesia. In addition, major and minor DRMs conferring resistance to NRTI were frequently found in RT genes derived from ART-experienced subjects.…”

Section: Textsupporting

confidence: 71%

Subtype Distribution and Drug Resistance Patterns Among HIV-1 Strains Prevalent in Makassar, Indonesia

Khairunisa

Megasari

Ueda

et al. 2023

AIDS Research and Human Retroviruses

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Human immunodeficiency virus type 1 (HIV-1) is characterized by a large degree of genetic variability because of high rates of recombination and mutation, sizable population sizes, and rapid replication. Therefore, the present study investigated HIV-1 subtype distribution and the appearance of drug resistance mutations (DRMs) in viruses that are prevalent in Makassar, South Sulawesi, Indonesia. The HIV-1 pol, env, and gag genes were amplified from 63 infected individuals and sequenced for a subtyping analysis.CRF01_AE was identified as the predominant HIV-1 circulating recombinant form (CRF) in Makassar, South Sulawesi, Indonesia. Subtype B and recombinant viruses containing CRF01_AE, CRF02_AG, and/or subtype B gene fragments were also detected. Several major DRMs against non-nucleoside reverse transcriptase inhibitors were found among antiretroviral therapy (ART)-experienced subjects, while ART-naive subjects did not possess any transmitted drug resistance. The prevalence of DRMs was very high among ART-experienced subjects; therefore, further surveillance is required in this region.

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Section: Textsupporting

confidence: 71%

Subtype Distribution and Drug Resistance Patterns Among HIV-1 Strains Prevalent in Makassar, Indonesia

Khairunisa

Megasari

Ueda

et al. 2023

AIDS Research and Human Retroviruses

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“…cDNA library construction and sequencing were as in our previous study [ 60 ]. Briefly, the PCR products were purified using Agencourt AMPure XP beads (Beckman Coulter, Brea, CA, USA) and quantified using a Qubit 3.0 Fluorometer (Life Technologies, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design

Zhang

Jiang

et al. 2022

BMC Immunol

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Background Identifying immunogens which can elicit effective T cell responses against human immunodeficiency virus type 1 (HIV-1) is important for developing a T-cell based vaccine. It has been reported that human leukocyte antigen (HLA)-B*13-restricted T-cell responses contributed to HIV control in subtype B′ and C infected individuals. However, the kinetics of B*13-restricted T-cell responses, viral evolution within epitopes, and the impact on disease progression in CRF01_AE subtype HIV-1-infected men who have sex with men (MSM) are not known. Results Interferon-γ ELISPOT assays and deep sequencing of viral RNAs were done in 14 early HLA-B*13-positive CRF01_AE subtype HIV-1-infected MSM. We found that responses to RQEILDLWV (Nef106–114, RV9), GQMREPRGSDI (Gag226–236, GI11), GQDQWTYQI (Pol487–498, GI9), and VQNAQGQMV (Gag135–143, VV9) were dominant. A higher relative magnitude of Gag-specific T-cell responses, contributed to viral control, whereas Nef-specific T-cell responses were associated with rapid disease progression. GI11 (Gag) was conserved and strong GI11 (Gag)-specific T-cell responses showed cross-reactivity with a dominant variant, M228I, found in 3/12 patients; GI11 (Gag)-specific T-cell responses were positively associated with CD4 T-cell counts (R = 0.716, P = 0.046). Interestingly, the GI9 (Pol) epitope was also conserved, but GI9 (Pol)-specific T-cell responses did not influence disease progression (P > 0.05), while a D490G variant identified in one patient did not affect CD4 T-cell counts. All the other epitopes studied [VV9 (Gag), RQYDQILIEI (Pol113–122, RI10), HQSLSPRTL (Gag144–152, HL9), and RQANFLGRL (Gag429–437, RL9)] developed escape mutations within 1 year of infection, which may have contributed to overall disease progression. Intriguingly, we found early RV9 (Nef)-specific T-cell responses were associated with rapid disease progression, likely due to escape mutations. Conclusions Our study strongly suggested the inclusion of GI11 (Gag) and exclusion of RV9 (Nef) for T-cell-based vaccine design for B*13-positive CRF01_AE subtype HIV-1-infected MSM and high-risk individuals.

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“…The ability of NGS-based genotyping in providing numerical data allows it to report the relative abundance of the variants and predict DRMs 5,17,20,21 . Recent studies have demonstrated the importance of identifying patients who are prone to virological failure due to an increasing evidence of LADRMs inducing immune system suppression, drug resistance aggregation, and death 5,[22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

A new sensitive and robust next-generation sequencing platform for HIV-1 drug resistance mutations testing

Yu¹,

Jin

Ma³

et al. 2021

Preprint

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Next-generation sequencing (NGS) is a trending new platform which allows cheap, quantitative, high-throughput, parallel sequencing for minority variants with frequencies less than 20% of the HIV-1 quasi-species. In clinical setting, these advantages are crucial for choosing antiretroviral drugs with low genetic barriers and will potentially benefit treatment outcomes. In this investigation, we implemented the Boxin HIV-1 NGS platform for genotyping the drug-resistance-associated variants in PR/RT regions. Plasmids with known mutations were used to analyze the accuracy, reproducibility, and reliability of the Boxin NGS assay. Variant frequencies reported by Boxin NGS and the theoretical value were highly concordant. The Bland-Altman plot and the coefficient of variation (7%) suggested that the method has excellent reproducibility and reliability. Sanger sequencing confirmed the existence of these known variants with frequencies equal or above 20%. 78 blood samples were obtained from AIDS patients and underwent PR/RT region genotyping by Sanger sequencing and Boxin NGS. 33 additional drug resistance mutations were identified by Boxin NGS, 23/33 mutations were minority variants with frequencies below 20%. 15 blood samples obtained from AIDS patients underwent PR/RT region genotyping by Sanger sequencing, Boxin NGS, and Vela NGS. The Bland-Altman plot suggested that the variant frequencies detected by Boxin and Vela were highly concordant. Moreover, Boxin NGS assay detected five more minority variants with frequencies ranged from 1% to 20%. In a series of samples collected from 2016 to 2017, Boxin NGS reported a M184V mutation with a frequency of 4.92%, 3 months earlier than this mutation was firstly detected by Vela NGS and Sanger sequencing. In conclusion, Boxin NGS had good accuracy, reproducibility, and reliability. Boxin NGS was highly concordant with Sanger sequencing and Vela NGS. In terms of genotyping HIV-1 variants in PR/RT regions, Boxin NGS was more cost-efficient and appeared to have increased sensitivity without compromising sequence accuracy.

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Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

Cited by 6 publications

References 38 publications

Subtype Distribution and Drug Resistance Patterns Among HIV-1 Strains Prevalent in Makassar, Indonesia

Subtype Distribution and Drug Resistance Patterns Among HIV-1 Strains Prevalent in Makassar, Indonesia

A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design

A new sensitive and robust next-generation sequencing platform for HIV-1 drug resistance mutations testing

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