التفاصيل البيبلوغرافية
| العنوان: |
Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir |
| المؤلفون: |
Maureen Oliveira, Ruxandra-Ilinca Ibanescu, Kaitlin Anstett, Thibault Mésplède, Jean-Pierre Routy, Marjorie A. Robbins, Bluma G. Brenner, the Montreal Primary HIV (PHI) Cohort Study Group |
| المصدر: |
Retrovirology, Vol 15, Iss 1, Pp 1-14 (2018) |
| بيانات النشر: |
BMC, 2018. |
| سنة النشر: |
2018 |
| المجموعة: |
LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: |
HIV-1, Integrase inhibitors, Antiretroviral drug resistance, Cell culture selections, Primary HIV infection isolates, HIV subtypes, Immunologic diseases. Allergy, RC581-607 |
| الوصف: |
Abstract Background Integrase strand transfer inhibitors (INSTIs) are recommended for first-line HIV therapy based on their relatively high genetic barrier to resistance. Although raltegravir (RAL) and elvitegravir (EVG) resistance profiles are well-characterized, resistance patterns for dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) remain largely unknown. Here, in vitro drug selections compared the development of resistance to DTG, BIC, CAB, EVG and RAL using clinical isolates from treatment-naïve primary HIV infection (PHI) cohort participants (n = 12), and pNL4.3 recombinant strains encoding patient-derived Integrase with (n = 5) and without (n = 5) the E157Q substitution. Results Patient-derived viral isolates were serially passaged in PHA-stimulated cord blood mononuclear cells in the presence of escalating concentrations of INSTIs over the course of 36–46 weeks. Drug resistance arose more rapidly in primary clinical isolates with EVG (12/12), followed by CAB (8/12), DTG (8/12) and BIC (6/12). For pNL4.3 recombinant strains encoding patient-derived integrase, the comparative genetic barrier to resistance was RAL > EVG > CAB > DTG and BIC. The E157Q substitution in integrase delayed the advent of resistance to INSTIs. With EVG, T66I/A, E92G/V/Q, T97A or R263K (n = 16, 3, 2 and 1, respectively) arose by weeks 8–16, followed by 1–4 accessory mutations, conferring high-level resistance (> 100-fold) by week 36. With DTG and BIC, solitary R263K (n = 27), S153F/Y (n = 7) H51Y (n = 2), Q146 R (n = 3) or S147G (n = 1) mutations conferred low-level ( |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1742-4690 |
| Relation: |
http://link.springer.com/article/10.1186/s12977-018-0440-3; https://doaj.org/toc/1742-4690 |
| DOI: |
10.1186/s12977-018-0440-3 |
| URL الوصول: |
https://doaj.org/article/265839ef403444f0a3ff603f2436c4a3 |
| رقم الانضمام: |
edsdoj.265839ef403444f0a3ff603f2436c4a3 |
| قاعدة البيانات: |
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