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

François Raffi, Abdel G. Babiker, Laura Richert, Jean Michel Molina, Elizabeth C. George, Andrea Antinori, Jose R. Arribas, Jesper Grarup, Fleur Hudson, Christine Schwimmer, Juliette Saillard, Cédrick Wallet, Per O. Jansson, Clotilde Allavena, Remko Van Leeuwen, Jean François Delfraissy, Stefano Vella, Geneviève Chêne, Anton Pozniak

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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 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.

Original languageEnglish
Pages (from-to)1942-1951
Number of pages10
JournalLancet
Volume384
Issue number9958
DOIs
Publication statusPublished - Nov 29 2014

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Tenofovir
Ritonavir
Reverse Transcriptase Inhibitors
HIV-1
Nucleotides
Therapeutics
Treatment Failure
Emtricitabine
Raltegravir Potassium
Darunavir
European Union
CD4 Lymphocyte Count
Nucleosides
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

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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. / 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.

In: Lancet, Vol. 384, No. 9958, 29.11.2014, p. 1942-1951.

Research output: Contribution to journalArticle

Raffi, F, Babiker, AG, Richert, L, Molina, JM, George, EC, Antinori, A, Arribas, JR, Grarup, J, Hudson, F, Schwimmer, C, Saillard, J, Wallet, C, Jansson, PO, Allavena, C, Van Leeuwen, R, Delfraissy, JF, Vella, S, Chêne, G & Pozniak, A 2014, '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', Lancet, vol. 384, no. 9958, pp. 1942-1951. https://doi.org/10.1016/S0140-6736(14)61170-3
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. / 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. In: Lancet. 2014 ; Vol. 384, No. 9958. pp. 1942-1951.
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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 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.",
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TY - JOUR

T1 - Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1

T2 - 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial

AU - Raffi, François

AU - Babiker, Abdel G.

AU - Richert, Laura

AU - Molina, Jean Michel

AU - George, Elizabeth C.

AU - Antinori, Andrea

AU - Arribas, Jose R.

AU - Grarup, Jesper

AU - Hudson, Fleur

AU - Schwimmer, Christine

AU - Saillard, Juliette

AU - Wallet, Cédrick

AU - Jansson, Per O.

AU - Allavena, Clotilde

AU - Van Leeuwen, Remko

AU - Delfraissy, Jean François

AU - Vella, Stefano

AU - Chêne, Geneviève

AU - Pozniak, Anton

PY - 2014/11/29

Y1 - 2014/11/29

N2 - 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.

AB - 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.

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JO - The Lancet

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