# Detection of HIV-1 Resistance Mutations to Antiretroviral Therapy and Cell Tropism in Russian Patients Using Next-Generation Sequencing

**Authors:** Artem Fadeev, Veronika Eder, Maria Pisareva, Valery Tsvetkov, Alexey Masharskiy, Kseniya Komissarova, Anna Ivanova, Nikita Yolshin, Andrey Komissarov, Alexey Mazus, Dmitry Lioznov

PMC · DOI: 10.3390/pathogens15020144 · Pathogens · 2026-01-28

## TL;DR

This study developed a next-generation sequencing protocol to detect HIV drug resistance and cell tropism in Russian patients, revealing high resistance to certain drugs and rare CXCR4 tropism.

## Contribution

A novel NGS-based protocol for HIV-1 resistance and tropism analysis tailored for Russian patients in 2024–2025.

## Key findings

- High resistance to NNRTIs and NRTIs was observed in treatment-experienced patients.
- Low resistance to protease and INSTIs was found across all groups.
- CXCR4 cell tropism was extremely rare in the studied population.

## Abstract

The use of antiretroviral therapy (ART) as the only effective way to control human immunodeficiency virus (HIV) infection results in HIV drug resistance. Next-generation sequencing (NGS) has become a common method for identifying drug-resistant variants and reducing analysis costs. The aim of this study was to develop an NGS-based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using NGS. HIV-1 drug resistance analysis was conducted using the Stanford University HIVdb database. CXCR4 cell tropism was predicted using an empirical rule classifier. A protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. High levels of resistance were observed to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced patients and to NNRTIs in treatment-naïve patients. Low levels of resistance were observed to protease and integrase strand transfer inhibitors (INSTIs). CXCR4 cell tropism was extremely rare. NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS-based protocols allows for performing ART efficiency and tropism monitoring at scale.

## Linked entities

- **Genes:** ERVW-4 (endogenous retrovirus group W member 4) [NCBI Gene 100616496], ERVW-1 (endogenous retrovirus group W member 1, envelope) [NCBI Gene 30816]

## Full-text entities

- **Genes:** ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) [NCBI Gene 3700] {aka GP120, H4P, IHRP, ITI-HC4, ITIHL1, PK-120}, Env [NCBI Gene 155971], CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, APOB (apolipoprotein B) [NCBI Gene 338] {aka FCHL2, FLDB, LDLCQ4, apoB-100, apoB-48}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, ERVK-6 (endogenous retrovirus group K member 6, envelope) [NCBI Gene 64006] {aka ERVK6, HERV-K(C7), HERV-K108, K-Rev, c-orf, cORF}, gag-pol (Gag-Pol) [NCBI Gene 155348]
- **Diseases:** infection (MESH:D007239), HIV infection (MESH:D015658), ART failure (MESH:D051437), multidrug resistance (MESH:D018088), Influenza (MESH:D007251), injury to (MESH:D014947), DR (MESH:D000069279)
- **Chemicals:** NVP (MESH:D019829), FPV (MESH:C426859), DOR (MESH:C000592662), ETR (MESH:C451734), AZT (MESH:D015215), LPV (MESH:D061466), DDI (MESH:D016049), NNRTI (-), ABC (MESH:C106538), ATV (MESH:D000069446), CAB (MESH:C584914), IDV (MESH:D019469), BIC (MESH:C000620396), EVG (MESH:C509700), TDF (MESH:D000068698), SQV (MESH:D019258), RAL (MESH:D000068898), RPV (MESH:D000068696), TPV (MESH:C107201), NFV (MESH:D019888), 3TC (MESH:D019259), DTG (MESH:C562325), D4T (MESH:D018119), EFV (MESH:C098320), DRV (MESH:D000069454), DPV (MESH:C481671)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** Y115F, Y188L, K101E, P225H, K at position 25, Q148R, Y318F, M184I, D67N, Y143R, Q58E, Q151M, E92Q, V179E, K103N, E138K, D232N, E92G, Q148H, F53L, M184V/I, L33F, S68G, Y181C, I54M, T66I, N155H, M184V, I54V, M46L, G163R, K43T, I47V, E138A, R263K, V11I, A62V, T66K, V106I, H221Y, G140A, G118R, T97A, M46I, S147G, K65R, L74M, K at position 11, Y143H, isoleucine at position 74, E157Q, G190A, V90I, G190S, I54S, L74I

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943137/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943137/full.md

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Source: https://tomesphere.com/paper/PMC12943137