HIV-1 Evolutionary Dynamics under Nonsuppressive Antiretroviral Therapy
| العنوان: | HIV-1 Evolutionary Dynamics under Nonsuppressive Antiretroviral Therapy |
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| المؤلفون: | Steven A. Kemp, Oscar J. Charles, Anne Derache, Werner Smidt, Darren P. Martin, Collins Iwuji, John Adamson, Katya Govender, Tulio de Oliveira, Francois Dabis, Deenan Pillay, Richard A. Goldstein, Ravindra K. Gupta |
| المساهمون: | University of Cambridge [UK] (CAM), University College of London [London] (UCL), Africa Health Research Institute [Durban/Mtubatuba] (AHRI), University of Cape Town, KwaZulu-Natal Research Innovation and Sequencing Platform [Durban, South Africa] (KRISP), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Deutsche Gesellschaft für Internationale Zusammenarbeit, Bill and Melinda Gates Foundation, Wellcome Trust, Admin, Oskar, Kemp, Steven [0000-0001-7077-6793], Gupta, Ravindra [0000-0001-9751-1808], Apollo - University of Cambridge Repository |
| المصدر: | mBio mBio, In press, ⟨10.1128/mbio.00269-22⟩ mBio, American Society for Microbiology, In press, ⟨10.1128/mbio.00269-22⟩ |
| بيانات النشر: | HAL CCSD, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Anti-HIV Agents, Human immunodeficiency virus, HIV Infections, Viral Load, Microbiology, Antiretroviral resistance, Anti-Retroviral Agents, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Drug Resistance, Viral, HIV Seropositivity, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Drug resistance evolution, Viremia, Clinical failure |
| الوصف: | International audience; Prolonged virologic failure on 2nd-line protease inhibitor (PI)-based antiretroviral therapy (ART) without emergence of major protease mutations is well recognized and provides an opportunity to study within-host evolution in long-term viremic individuals. Using next-generation sequencing and in silico haplotype reconstruction, we analyzed whole-genome sequences from longitudinal plasma samples of eight chronically infected HIV-1-positive individuals failing 2nd-line regimens from the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) trial. On nonsuppressive ART, there were large fluctuations in synonymous and nonsynonymous variant frequencies despite stable viremia. Reconstructed haplotypes provided evidence for selective sweeps during periods of partial adherence, and viral haplotype competition, during periods of low drug exposure. Drug resistance mutations in reverse transcriptase (RT) were used as markers of viral haplotypes in the reservoir, and their distribution over time indicated recombination. We independently observed linkage disequilibrium decay, indicative of recombination. These data highlight dramatic changes in virus population structure that occur during stable viremia under nonsuppressive ART. IMPORTANCE HIV-1 infections are most commonly initiated with a single founder virus and are characterized by extensive inter- and intraparticipant genetic diversity. However, existing literature on HIV-1 intrahost population dynamics is largely limited to untreated infections, predominantly in subtype B-infected individuals. The manuscript characterizes viral population dynamics in long-term viremic treatment-experienced individuals, which has not been previously characterized. These data are particularly relevant for understanding HIV dynamics but can also be applied to other RNA viruses. With this unique data set we propose that the virus is highly unstable, and we have found compelling evidence of HIV-1 within-host viral diversification, recombination, and haplotype competition during nonsuppressive ART. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2161-2129 2150-7511 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b9f419a1821b2f32d9d0795f7f5a6e6Test https://hal.science/hal-03665249Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6b9f419a1821b2f32d9d0795f7f5a6e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21612129 21507511 |
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