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.
Antiretroviral Therapy, Highly Active
Biomarkers
CD4 Lymphocyte Count
Female
HIV Infections
/ drug therapy
HIV Integrase Inhibitors
/ administration & dosage
HIV Protease Inhibitors
/ administration & dosage
Humans
Male
Medication Adherence
Middle Aged
Nitriles
Pyridazines
/ administration & dosage
Pyrimidines
Quality of Life
Raltegravir Potassium
/ administration & dosage
Reverse Transcriptase Inhibitors
/ administration & dosage
Time Factors
Treatment Outcome
Viral Load
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
01 09 2019
01 09 2019
Historique:
received:
04
02
2019
revised:
18
04
2019
accepted:
23
04
2019
pubmed:
4
7
2019
medline:
20
8
2020
entrez:
4
7
2019
Statut:
ppublish
Résumé
Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. 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. 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. Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.
Sections du résumé
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.
Identifiants
pubmed: 31269208
pii: 5528001
doi: 10.1093/jac/dkz224
doi:
Substances chimiques
Biomarkers
0
HIV Integrase Inhibitors
0
HIV Protease Inhibitors
0
Nitriles
0
Pyridazines
0
Pyrimidines
0
Reverse Transcriptase Inhibitors
0
etravirine
0C50HW4FO1
Raltegravir Potassium
43Y000U234
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2742-2751Investigateurs
Louis Bernard
(L)
Julie Bottero
(J)
Olivier Bouchaud
(O)
Christian Chidiac
(C)
Claudine Duvivier
(C)
Cécile Goujard
(C)
Maria delMarGutiérrez
(M)
Esteban Martinez
(E)
Jean-Michel Molina
(JM)
Philippe Morlat
(P)
Alissa Naqvi
(A)
Daniel Podzamczer
(D)
Isabelle Poizot-Martin
(I)
François Raffi
(F)
Jacques Reynes
(J)
Dominique Salmon-Céron
(D)
Anne Simon
(A)
Marc-Antoine Valantin
(MA)
Laurence Weiss
(L)
Yazdan Yazdanpanah
(Y)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.