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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 and Schwimmer, Christine, et al. (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.

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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
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The Lancet
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384
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9958
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Elsevier Limited
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1474-547X
DOI
10.1016/S0140-6736(14)61170-3
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English
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2017-10-08 23:35:56
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2017-11-02 09:14:14
@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 ,  and Odermarsky, Michal},
  issn         = {1474-547X},
  keyword      = {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 Limited},
  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},
  volume       = {384},
  year         = {2014},
}