Publication:
Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial

Issued Date

2017-11-01

Resource Type

Article

ISSN

23523018

DOI

10.1016/S2352-3018(17)30128-5

Other identifier(s)

2-s2.0-85029227305

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Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet HIV. Vol.4, No.11 (2017), e486-e494

Suggested Citation

Pedro Cahn, Richard Kaplan, Paul E. Sax, Kathleen Squires, Jean Michel Molina, Anchalee Avihingsanon, Winai Ratanasuwan, Evelyn Rojas, Mohammed Rassool, Mark Bloch, Linos Vandekerckhove, Peter Ruane, Yazdan Yazdanpanah, Christine Katlama, Xia Xu, Anthony Rodgers, Lilly East, Larissa Wenning, Sandy Rawlins, Brenda Homony, Peter Sklar, Bach Yen Nguyen, Randi Leavitt, Hedy Teppler, P. E. Cahn, I. Cassetti, M. Losso, M. T. Bloch, N. Roth, J. McMahon, R. J. Moore, D. Smith, N. Clumeck, L. Vanderkerckhove, B. Vandercam, M. Moutschen, J. Baril, B. Conway, F. Smaill, G. H.R. Smith, A. Rachlis, S. L. Walmsley, C. Perez, M. Wolff, M. F. Lasso, C. E. Chahin, J. D. Velez, O. Sussmann, J. Reynes, C. Katlama, Y. Yazdanpanah, S. Ferret, J. Durant, C. Duvivier, I. Poizot-Martin, F. Ajana, J. K. Rockstroh, G. Faetkanheuer, S. Esser, H. Jaeger, O. Degen, M. Bickel, J. Bogner, K. Arasteh, H. Hartl, A. Stoehr, E. M. Rojas, E. Arathoon, L. D. Gonzalez, C. R. Mejia, E. Shahar, D. Turner, I. Levy, Z. Sthoeger, H. Elinav, A. Gori, A. D.Arminio Monforte, G. Di Perri, A. Lazzarin, G. Rizzardini, A. Antinori, B. M. Celesia, F. Maggiolo, T. S. Chow, C. K.C. Lee, R. Iskandar Shah Raja Azwa, M. Mustafa, M. Oyanguren, R. A. Castillo, L. Hercilla, C. Echiverri, F. Maltez, JG Saraiva da Cunha, I. Neves, E. Teofilo, R. Serrao, F. Nagimova, I. Khaertynova, E. Orlova-Morozova, E. Voronin Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. The Lancet HIV. Vol.4, No.11 (2017), e486-e494. doi:10.1016/S2352-3018(17)30128-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42665

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Title

Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial

Author(s)

Pedro Cahn
 Richard Kaplan
 Paul E. Sax
 Kathleen Squires
 Jean Michel Molina
 Anchalee Avihingsanon
 Winai Ratanasuwan
 Evelyn Rojas
 Mohammed Rassool
 Mark Bloch
 Linos Vandekerckhove
 Peter Ruane
 Yazdan Yazdanpanah
 Christine Katlama
 Xia Xu
 Anthony Rodgers
 Lilly East
 Larissa Wenning
 Sandy Rawlins
 Brenda Homony
 Peter Sklar
 Bach Yen Nguyen
 Randi Leavitt
 Hedy Teppler
 P. E. Cahn
 I. Cassetti
 M. Losso
 M. T. Bloch
 N. Roth
 J. McMahon
 R. J. Moore
 D. Smith
 N. Clumeck
 L. Vanderkerckhove
 B. Vandercam
 M. Moutschen
 J. Baril
 B. Conway
 F. Smaill
 G. H.R. Smith
 A. Rachlis
 S. L. Walmsley
 C. Perez
 M. Wolff
 M. F. Lasso
 C. E. Chahin
 J. D. Velez
 O. Sussmann
 J. Reynes
 C. Katlama
 Y. Yazdanpanah
 S. Ferret
 J. Durant
 C. Duvivier
 I. Poizot-Martin
 F. Ajana
 J. K. Rockstroh
 G. Faetkanheuer
 S. Esser
 H. Jaeger
 O. Degen
 M. Bickel
 J. Bogner
 K. Arasteh
 H. Hartl
 A. Stoehr
 E. M. Rojas
 E. Arathoon
 L. D. Gonzalez
 C. R. Mejia
 E. Shahar
 D. Turner
 I. Levy
 Z. Sthoeger
 H. Elinav
 A. Gori
 A. D.Arminio Monforte
 G. Di Perri
 A. Lazzarin
 G. Rizzardini
 A. Antinori
 B. M. Celesia
 F. Maggiolo
 T. S. Chow
 C. K.C. Lee
 R. Iskandar Shah Raja Azwa
 M. Mustafa
 M. Oyanguren
 R. A. Castillo
 L. Hercilla
 C. Echiverri
 F. Maltez
 JG Saraiva da Cunha
 I. Neves
 E. Teofilo
 R. Serrao
 F. Nagimova
 I. Khaertynova
 E. Orlova-Morozova
 E. Voronin

Other Contributor(s)

Fundacion Huesped
 Desmond Tutu HIV Foundation
 Brigham and Women's Hospital
 Thomas Jefferson University
 Hôpital Saint-Louis
 Chulalongkorn University
 Mahidol University
 Cericap Multiclinicas
 University of Witwatersrand
 Holdsworth House Medical Practice
 Universiteit Ghent, Faculteit Geneeskunde en Gezondheidswetenschappen
 Ruane Medical and Liver Health Institute
 Hôpital Bichat-Claude-Bernard AP-HP
 Hôpital Universitaire Pitié Salpêtrière
 Merck & Co., Inc.

Abstract

© 2017 Elsevier Ltd Background Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. Methods In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than −10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. Findings Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI −4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. Interpretation A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. Funding Merck & Co, Inc.

Keyword(s)

Immunology and Microbiology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/42665

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Scopus 2016-2017