Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates
The development of animal models undergoing long-term antiretroviral treatment (ART) makes it possible to understand a number of immunological, virological, and pharmacological issues, key factors in the management of HIV infection. We aimed to pharmacologically validate a non-human primate (NHP) mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2282 |
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| author | Thibaut Gelé Hélène Gouget Nathalie Dereuddre-Bosquet Valérie Furlan Roger Le Grand Olivier Lambotte Delphine Desjardins Aurélie Barrail-Tran |
| author_facet | Thibaut Gelé Hélène Gouget Nathalie Dereuddre-Bosquet Valérie Furlan Roger Le Grand Olivier Lambotte Delphine Desjardins Aurélie Barrail-Tran |
| author_sort | Thibaut Gelé |
| collection | DOAJ |
| description | The development of animal models undergoing long-term antiretroviral treatment (ART) makes it possible to understand a number of immunological, virological, and pharmacological issues, key factors in the management of HIV infection. We aimed to pharmacologically validate a non-human primate (NHP) model treated in the long term with antiretroviral drugs after infection with the pathogenic SIVmac251 strain. A single-dose pharmacokinetic study of tenofovir disoproxil fumarate, emtricitabine, and dolutegravir was first conducted on 13 non-infected macaques to compare three different routes of administration. Then, 12 simian immunodeficiency virus (SIV)-infected (SIV<sup>+</sup>) macaques were treated with the same regimen for two years. Drug monitoring, virological efficacy, and safety were evaluated throughout the study. For the single-dose pharmacokinetic study, 24-h post-dose plasma concentrations for all macaques were above or close to 90% inhibitory concentrations and consistent with human data. During the two-year follow-up, the pharmacological data were consistent with those observed in humans, with low inter- and intra-individual variability. Rapid and sustained virological efficacy was observed for all macaques, with a good safety profile. Overall, our SIV<sup>+</sup> NHP model treated with the ART combination over a two-year period is suitable for investigating the question of pharmacological sanctuaries in HIV infection and exploring strategies for an HIV cure. |
| first_indexed | 2024-03-09T18:45:23Z |
| format | Article |
| id | doaj.art-c22b7677f8bc4894bae9d1f72940c31a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:45:23Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c22b7677f8bc4894bae9d1f72940c31a2023-11-24T06:19:37ZengMDPI AGPharmaceutics1999-49232022-10-011411228210.3390/pharmaceutics14112282Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human PrimatesThibaut Gelé0Hélène Gouget1Nathalie Dereuddre-Bosquet2Valérie Furlan3Roger Le Grand4Olivier Lambotte5Delphine Desjardins6Aurélie Barrail-Tran7Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, FranceImmunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, FranceImmunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, FranceService de Pharmacologie-Toxicologie, Hôpital Bicêtre, AP-HP. Université Paris-Saclay, 94275 Le Kremlin-Bicêtre, FranceImmunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, FranceImmunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Service de Médecine Interne Immunologie Clinique, Hôpital Bicêtre, Université Paris-Saclay, AP-HP, Inserm, CEA, 94275 Le Kremlin-Bicêtre, FranceImmunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, FranceImmunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Service de Pharmacie, Hôpital Bicêtre, Université Paris-Saclay, AP-HP, Inserm, CEA, 94275 Le Kremlin-Bicêtre, FranceThe development of animal models undergoing long-term antiretroviral treatment (ART) makes it possible to understand a number of immunological, virological, and pharmacological issues, key factors in the management of HIV infection. We aimed to pharmacologically validate a non-human primate (NHP) model treated in the long term with antiretroviral drugs after infection with the pathogenic SIVmac251 strain. A single-dose pharmacokinetic study of tenofovir disoproxil fumarate, emtricitabine, and dolutegravir was first conducted on 13 non-infected macaques to compare three different routes of administration. Then, 12 simian immunodeficiency virus (SIV)-infected (SIV<sup>+</sup>) macaques were treated with the same regimen for two years. Drug monitoring, virological efficacy, and safety were evaluated throughout the study. For the single-dose pharmacokinetic study, 24-h post-dose plasma concentrations for all macaques were above or close to 90% inhibitory concentrations and consistent with human data. During the two-year follow-up, the pharmacological data were consistent with those observed in humans, with low inter- and intra-individual variability. Rapid and sustained virological efficacy was observed for all macaques, with a good safety profile. Overall, our SIV<sup>+</sup> NHP model treated with the ART combination over a two-year period is suitable for investigating the question of pharmacological sanctuaries in HIV infection and exploring strategies for an HIV cure.https://www.mdpi.com/1999-4923/14/11/2282tenofovir/emtricitabine/dolutegravirpharmacokineticslong-term treatmentnon-human primate |
| spellingShingle | Thibaut Gelé Hélène Gouget Nathalie Dereuddre-Bosquet Valérie Furlan Roger Le Grand Olivier Lambotte Delphine Desjardins Aurélie Barrail-Tran Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates Pharmaceutics tenofovir/emtricitabine/dolutegravir pharmacokinetics long-term treatment non-human primate |
| title | Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates |
| title_full | Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates |
| title_fullStr | Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates |
| title_full_unstemmed | Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates |
| title_short | Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates |
| title_sort | pharmacological validation of long term treatment with antiretroviral drugs in a model of siv infected non human primates |
| topic | tenofovir/emtricitabine/dolutegravir pharmacokinetics long-term treatment non-human primate |
| url | https://www.mdpi.com/1999-4923/14/11/2282 |
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