Christine Katlama1,2, Lambert Assoumou2, Marc-Antoine Valantin1,2, Cathia Soulié2,3, Esteban Martinez4, Lydie Béniguel2, Olivier Bouchaud5,6, François Raffi7, Jean-Michel Molina8, Soraya Fellahi9, Gilles Peytavin10, Anne-Geneviève Marcelin3, Sami Kolta11, Jacqueline Capeau9, Severine Gibowski12, Fanny Cardon12, Jacques Reynes13, Dominique Costagliola2. 1. Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, Paris, France. 2. Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), Paris, France. 3. APHP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France. 4. Infectious Diseases Unit, Hospital Clinic and University of Barcelona, Spain. 5. Assistance Publique-Hôpitaux de Paris (APHP), Centre Hospitalier Universitaire Avicenne, Service des Maladies Infectieuses et Tropicales, Bobigny, France. 6. Université Paris 13, IMEA-Fondation Internationale Léon Mba, Paris, France. 7. INSERM CIC 1413, Université de Nantes, Département des Maladies Infectieuses, Hôpital Hôtel-Dieu, Nantes, France. 8. Université Paris Diderot, Paris, France, Sorbonne Paris Cité, APHP, Hôpital Saint-Louis, Paris, France. 9. Sorbonne Université, INSERM UMRS_938, Institut Hospitalo-Universitaire de Cardio-métabolisme et Nutrition (ICAN), Paris, France. 10. INSERM UMR 1137, Université Paris 7, Laboratoire de Pharmacologie-Toxicologie, Hôpital Bichat-Claude Bernard, APHP, Paris, France. 11. Département de rhumatologie, Hôpital Cochin, Paris, France - INSERM UMR-1153, Paris, France. 12. ANRS, France Recherche Nord & Sud Sida-HIV Hépatites, Agence autonome de l'INSERM, Paris, France. 13. Département de maladies infectieuses, UMI 233 INSERM U1175, CHU de Montpellier, Montpellier, France.
Abstract
BACKGROUND: Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. METHODS: The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. RESULTS: One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%-99.9%) at week 48 and 98.7% (95% CI = 95.0%-99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%-97.5%) at week 48 and 92.7% (95% CI = 87.5%-95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (-8.1%), soluble CD14 decreased (-27%, P < 0.001) bone mineral density improved and BMI increased. CONCLUSIONS: Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.
BACKGROUND: Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. METHODS: The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. RESULTS: One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%-99.9%) at week 48 and 98.7% (95% CI = 95.0%-99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%-97.5%) at week 48 and 92.7% (95% CI = 87.5%-95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (-8.1%), soluble CD14 decreased (-27%, P < 0.001) bone mineral density improved and BMI increased. CONCLUSIONS:Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.
Authors: Benson M Hamooya; Lloyd B Mulenga; Sepiso K Masenga; Isaac Fwemba; Lameck Chirwa; Mpanji Siwingwa; Hikabasa Halwiindi; John R Koethe; Loren Lipworth; Douglas C Heimburger; Patrick Musonda; Wilbroad Mutale Journal: Medicine (Baltimore) Date: 2021-04-09 Impact factor: 1.817
Authors: Sauzanne Khalilieh; Ka Lai Yee; Rosa Sanchez; S Aubrey Stoch; Larissa Wenning; Marian Iwamoto Journal: Clin Drug Investig Date: 2020-10 Impact factor: 2.859