Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1 : 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial
(2014) In The Lancet 384(9958). p.51-1942- Abstract
BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen.
METHODS: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent... (More)
BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen.
METHODS: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962.
FINDINGS: Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively).
INTERPRETATION: Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL.
FUNDING: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.
(Less)
- author
- Raffi, François
; Babiker, Abdel G.
; Richert, Laura
; Molina, Jean-Michel
; George, Elizabeth C.
; Antinori, Andrea
; Arribas, Jose R
; Grarup, Jesper
; Hudson, Fleur
; Schwimmer, Christine
; Saillard, Juliette
; Wallet, Cédrick
; Jansson, Per O.
; Allavena, Clotilde
; Van Leeuwen, Remko
; Delfraissy, Jean-François
; Vella, Stefano
; Chêne, Geneviève
; Pozniak, Anton
and Odermarsky, Michal
LU
(Less) - author collaboration
- organization
- publishing date
- 2014-11-29
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adenine, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Cholesterol, HDL, Cholesterol, LDL, Darunavir, Deoxycytidine, Drug Resistance, Viral, Drug Therapy, Combination, Emtricitabine, Female, HIV Infections, HIV-1, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Organophosphonates, Pyrrolidinones, Raltegravir Potassium, Ritonavir, Sulfonamides, Tenofovir, Treatment Outcome, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
- in
- The Lancet
- volume
- 384
- issue
- 9958
- pages
- 10 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:25103176
- scopus:84919458152
- ISSN
- 1474-547X
- DOI
- 10.1016/S0140-6736(14)61170-3
- language
- English
- LU publication?
- yes
- id
- b5cc5f2a-c64d-43f3-91ec-8267746aa636
- date added to LUP
- 2017-10-08 23:35:56
- date last changed
- 2024-06-24 00:32:01
@article{b5cc5f2a-c64d-43f3-91ec-8267746aa636,
abstract = {{<p>BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen.</p><p>METHODS: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962.</p><p>FINDINGS: Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively).</p><p>INTERPRETATION: Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL.</p><p>FUNDING: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.</p>}},
author = {{Raffi, François and Babiker, Abdel G. and Richert, Laura and Molina, Jean-Michel and George, Elizabeth C. and Antinori, Andrea and Arribas, Jose R and Grarup, Jesper and Hudson, Fleur and Schwimmer, Christine and Saillard, Juliette and Wallet, Cédrick and Jansson, Per O. and Allavena, Clotilde and Van Leeuwen, Remko and Delfraissy, Jean-François and Vella, Stefano and Chêne, Geneviève and Pozniak, Anton and Odermarsky, Michal}},
issn = {{1474-547X}},
keywords = {{Adenine; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cholesterol, HDL; Cholesterol, LDL; Darunavir; Deoxycytidine; Drug Resistance, Viral; Drug Therapy, Combination; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Organophosphonates; Pyrrolidinones; Raltegravir Potassium; Ritonavir; Sulfonamides; Tenofovir; Treatment Outcome; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't}},
language = {{eng}},
month = {{11}},
number = {{9958}},
pages = {{51--1942}},
publisher = {{Elsevier}},
series = {{The Lancet}},
title = {{Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1 : 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial}},
url = {{http://dx.doi.org/10.1016/S0140-6736(14)61170-3}},
doi = {{10.1016/S0140-6736(14)61170-3}},
volume = {{384}},
year = {{2014}},
}