Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study

Christine Katlama (1, 2, 3) , Lambert Assoumou (1, 3) , Marc Antoine Valantin (1, 2, 3) , Cathia Soulié (1, 3, 2) , Esteban Martinez , Lydie Beniguel (1, 3) , Olivier Bouchaud (4) , Francois Raffi , Jean Michel Molina (5) , Soraya Fellahi (6, 7, 3) , Gilles Peytavin (8) , Anne Geneviève Marcelin (2) , Sami Kolta , Jacqueline Capeau (7, 6, 3) , Severine Gibowski (9) , Fanny Cardon (9) , Jacques Reynes (10) , Dominique Costagliola (1, 3)

1 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
2 CHU Pitié-Salpêtrière [AP-HP]
3 SU - Sorbonne Université
4 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
5 AP-HP - Hopital Saint-Louis [AP-HP]
6 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
7 CRSA - Centre de Recherche Saint-Antoine
8 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
9 ANRS France Recherche Nord & sud Sida-hiv hépatites
10 CHU Montpellier

Background:Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageingHIV-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 evaluatingthe 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 pro-portion of participants with virological success, defined by the absence of virological failure up to week 48. Mainsecondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and in-flammatory markers. The study was designed to show an efficacy.90%, assuming a success rate95%, with apower 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 suppres-sion 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in99.4% of participants (95% CI"95.6%–99.9%) at week 48 and 98.7% (95% CI"95.0%–99.7%) at week 96. Twovirological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eightparticipants 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 frac-tions improved (P,0.001), CD4/CD8 ratio increased, IFNc-induced protein 10 (IP-10) decreased (#8.1%), solubleCD14 decreased (#27%,P,0.001) bone mineral density improved and BMI increased.Conclusions:Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressedageing patients.

Domaines: Pharmacologie; Maladies infectieuses

Christine Katlama, Lambert Assoumou, Marc Antoine Valantin, Cathia Soulié, Esteban Martinez, et al.. Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study. Journal of Antimicrobial Chemotherapy, 2019, 74 (9), pp.2742-2751. ⟨10.1093/jac/dkz224⟩. ⟨hal-02476360⟩