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
Por:
Katlama, C, Assoumou, L, Soulie, C, Beniguel, L, Fellahi, S, Peytavin, G, Marcelin, AG, Kolta, S, Capeau, J, Gibowski, S, Cardon, F, Costagliola, D, Bernard, L, Bottero, J, Bouchaud, O, Chidiac, C, Duvivier, C, Goujard, C, Gutierrez, MD, Martinez, E, Molina, JM, Morlat, P, Naqvi, A, Podzamczer, D, Poizot-Martin, I, Raffi, F, Reynes, J, Salmon-Ceron, D, Simon, A, Valantin, MA, Weiss, L, Yazdanpanah, Y
Publicada:
1 sep 2019
Resumen:
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, IFN -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.
Filiaciones:
Katlama, C:
Hop La Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, Paris, France
Sorbonne Univ, INSERM, IPLESP, Paris, France
Assoumou, L:
Sorbonne Univ, INSERM, IPLESP, Paris, France
Soulie, C:
Sorbonne Univ, INSERM, IPLESP, Paris, France
Hop La Pitie Salpetriere, AP HP, Virol Lab, Paris, France
Beniguel, L:
Sorbonne Univ, INSERM, IPLESP, Paris, France
Fellahi, S:
Sorbonne Univ, Inst Hosp Univ Cardiometab & Nutr ICAN, INSERM, UMRS 938, Paris, France
Peytavin, G:
Univ Paris 07, Hop Bichat Claude Bernard, AP HP, Lab Pharmacol Toxicol,INSERM,UMR 1137, Paris, France
Marcelin, AG:
Hop La Pitie Salpetriere, AP HP, Virol Lab, Paris, France
Kolta, S:
Hop Cochin, Dept Rheumatol, Paris, France
INSERM, UMR 1153, Paris, France
Capeau, J:
Sorbonne Univ, Inst Hosp Univ Cardiometab & Nutr ICAN, INSERM, UMRS 938, Paris, France
Gibowski, S:
INSERM, ANRS, France Rech Nord & Sud Sida HIV Hepatites, Agence Autonome, Paris, France
Cardon, F:
INSERM, ANRS, France Rech Nord & Sud Sida HIV Hepatites, Agence Autonome, Paris, France
Costagliola, D:
Sorbonne Univ, INSERM, IPLESP, Paris, France
Bernard, L:
Hop Bretonneau, Tours, France
Bottero, J:
Hop Jean Verdier, Bondy, France
Bouchaud, O:
Ctr Hosp Univ Avicenne, AP HP, Serv Malad Infect & Trop, Bobigny, France
Univ Paris 13, IMEA Fdn Int Leon Mba, Paris, France
Hop Avicenne, Bobigny, France
Chidiac, C:
Hop Croix Rousse, Lyon, France
Duvivier, C:
Hop Necker Enfants Malad, Paris, France
Goujard, C:
Hop Bicetre, Le Kremlin Bicetre, France
Gutierrez, MD:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Martinez, E:
Hosp Clin Barcelona, Infect Dis Unit, Barcelona, Spain
Univ Barcelona, Barcelona, Spain
Hosp Clin Barcelona, Barcelona, Spain
Molina, JM:
Univ Paris Diderot, Paris, France
Hop St Louis, AP HP, Sorbonne Paris Cite, Paris, France
Hop St Louis, Paris, France
Morlat, P:
Hop St Andre, Bordeaux, France
Naqvi, A:
Hop Archet, Nice, France
Podzamczer, D:
Bellvitge Hosp, Barcelona, Spain
Poizot-Martin, I:
Hop St Marguerite, Marseille, France
Raffi, F:
Univ Nantes, Hop Hotel Dieu, INSERM, CIC 1413,Dept Malad Infect, Nantes, France
CHU Hotel Dieu, Nantes, France
Reynes, J:
CHU Montpellier, INSERM, Dept Malad Infect, UMI 233,U1175, Montpellier, France
Hop Gui de Chauliac, Montpellier, France
Salmon-Ceron, D:
Hop Cochin, Paris, France
Simon, A:
Hop La Pitie Salpetriere, Paris, France
Valantin, MA:
Hop La Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, Paris, France
Sorbonne Univ, INSERM, IPLESP, Paris, France
Hop La Pitie Salpetriere, Paris, France
Weiss, L:
Hop Europeen Georges Pompidou, Paris, France
Yazdanpanah, Y:
Hop Bichat Claude Bernard, Paris, France
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