Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates
Thibaut Gelé,
Hélène Gouget,
Nathalie Dereuddre-Bosquet,
Valérie Furlan,
Roger Le Grand,
Olivier Lambotte,
Delphine Desjardins,
Aurélie Barrail-Tran
Affiliations
Thibaut Gelé
Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, France
Hélène Gouget
Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, France
Nathalie Dereuddre-Bosquet
Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, France
Valérie Furlan
Service de Pharmacologie-Toxicologie, Hôpital Bicêtre, AP-HP. Université Paris-Saclay, 94275 Le Kremlin-Bicêtre, France
Roger Le Grand
Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, France
Olivier Lambotte
Immunologie 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, France
Delphine Desjardins
Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, France
Aurélie Barrail-Tran
Immunologie des Maladies Virales, Auto-Immunes, Hématologiques et Bactériennes, Service de Pharmacie, Hôpital Bicêtre, Université Paris-Saclay, AP-HP, Inserm, CEA, 94275 Le Kremlin-Bicêtre, France
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+) 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+ 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.