Baseline Lenacapavir Resistance and Capsid Variability in Bulgaria: A Next-Generation Sequencing Study of Newly Diagnosed HIV-1 Infections.
7 affiliations
- 1National Reference Confirmatory Laboratory of HIV, National Center of Infectious and Parasitic Diseases (NCIPD), 1504 Sofia, Bulgaria.
- 2National Reference Laboratory of Immunology, NCIPD, 1504 Sofia, Bulgaria.
- 3University Multi-Profile Hospital for Active Treatment of Infectious and Parasitic Diseases, 1606 Sofia, Bulgaria.
- 4Department of Infectious Diseases, Parasitology and Tropical Medicine, MU-Plovdiv, 4002 Plovdiv, Bulgaria.
- 5Clinic of Infectious Diseases, University Hospital "Prof. Dr. G. Stranski", 5800 Pleven, Bulgaria.
- 6Clinic of Infectious Diseases, University Hospital "Prof. Dr. St. Kirkovich", 6003 Stara Zagora, Bulgaria.
- 7University Hospital "St. Marina", 9010 Varna, Bulgaria.
Abstract
Lenacapavir, the first approved HIV-1 capsid inhibitor, is now being introduced for both treatment and pre-exposure prophylaxis, yet the capsid-coding region lies outside the pol fragment examined in routine genotypic resistance testing, and baseline data on capsid variability remain scarce, particularly in epidemics dominated by non-B lineages. We applied next-generation sequencing of the HIV-1 gag gene to 103 lenacapavir-naive individuals newly diagnosed in Bulgaria between 2023 and 2025. Nine lineages were identified. Subtype B accounted for 46.6% of the sequences, whereas non-B lineages together predominated (53.4%), led by sub-subtype F1 (13.6%) and CRF01_AE (8.7%); a further 10.7% remained unassigned and grouped predominantly with BF1 recombinant references. The distribution of these lineages differed significantly according to the probable route of transmission (p = 0.007). No major lenacapavir resistance-associated mutation was detected (0 of 103; 95% CI 0.0-3.6). Substitutions at position 107 were the only changes observed at a resistance-associated position: T107S in two individuals and a T107T/S mixture in one (2.9% combined). Notably, the two T107S sequences formed a CRF01_AE pair supported by a bootstrap value of 100, indicating that this accessory polymorphism can persist in closely related viruses. All viruses were genotypically predicted to remain susceptible to lenacapavir. These findings establish a molecular baseline for capsid surveillance in Bulgaria, a South-Eastern European country with a genetically diverse HIV-1 epidemic.
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BibTeX
@article{alexiev2026baseline,
title = {{Baseline Lenacapavir Resistance and Capsid Variability in Bulgaria: A Next-Generation Sequencing Study of Newly Diagnosed HIV-1 Infections.}},
author = {Ivailo Alexiev and Aleksandra Partsuneva and Reneta Dimitrova and Asya Kostadinova and Anna Gancheva and Lyubomira Grigorova and Kristina Stoyanova and Maria Nikolova and Radoslava Emilova and Nina Yancheva and Dimitar Strashimirov and Ivan Baltadzhiev and Tsetsa Doychinova and Pavlina Parusheva and Ivelina Todorova},
journal = {Pathogens (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/pathogens15101011},
url = {https://europepmc.org/article/MED/42931163},
note = {CC BY},
}
RIS
TY - JOUR
TI - Baseline Lenacapavir Resistance and Capsid Variability in Bulgaria: A Next-Generation Sequencing Study of Newly Diagnosed HIV-1 Infections.
AU - Ivailo Alexiev
AU - Aleksandra Partsuneva
AU - Reneta Dimitrova
AU - Asya Kostadinova
AU - Anna Gancheva
AU - Lyubomira Grigorova
AU - Kristina Stoyanova
AU - Maria Nikolova
AU - Radoslava Emilova
AU - Nina Yancheva
AU - Dimitar Strashimirov
AU - Ivan Baltadzhiev
AU - Tsetsa Doychinova
AU - Pavlina Parusheva
AU - Ivelina Todorova
PY - 2026
DA - 2026/09/24
JO - Pathogens (Basel, Switzerland)
DO - 10.3390/pathogens15101011
UR - https://europepmc.org/article/MED/42931163
AB - Lenacapavir, the first approved HIV-1 capsid inhibitor, is now being introduced for both treatment and pre-exposure prophylaxis, yet the capsid-coding region lies outside the pol fragment examined in routine genotypic resistance testing, and baseline data on capsid variability remain scarce, particularly in epidemics dominated by non-B lineages. We applied next-generation sequencing of the HIV-1 gag gene to 103 lenacapavir-naive individuals newly diagnosed in Bulgaria between 2023 and 2025. Nine lineages were identified. Subtype B accounted for 46.6% of the sequences, whereas non-B lineages together predominated (53.4%), led by sub-subtype F1 (13.6%) and CRF01_AE (8.7%); a further 10.7% remained unassigned and grouped predominantly with BF1 recombinant references. The distribution of these lineages differed significantly according to the probable route of transmission (p = 0.007). No major lenacapavir resistance-associated mutation was detected (0 of 103; 95% CI 0.0-3.6). Substitutions at position 107 were the only changes observed at a resistance-associated position: T107S in two individuals and a T107T/S mixture in one (2.9% combined). Notably, the two T107S sequences formed a CRF01_AE pair supported by a bootstrap value of 100, indicating that this accessory polymorphism can persist in closely related viruses. All viruses were genotypically predicted to remain susceptible to lenacapavir. These findings establish a molecular baseline for capsid surveillance in Bulgaria, a South-Eastern European country with a genetically diverse HIV-1 epidemic.
SN - 2076-0817
ER -