Raltegravir non-inferior to nucleoside based regimens in second-line therapy with lopinavir/ritonavir over 96 weeks: a randomised open label study for the treatment of HIV-1 infection

Janaki Amin, Mark A. Boyd, Nagalingeswaran Kumarasamy, Cecilia L. Moore, Marcello H. Losso, Chidi A. Nwizu, Lerato Mohapi, Stephen J. Kerr, Annette H. Sohn, Hedy Teppler, Boris Renjifo, Jean Michel Molina, Sean Emery, David A. Cooper, SECOND-LINE

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Abstract

Objective: To determine the durability over 96 weeks of safety and efficacy of lopinavir/ritonavir (LPV/r) and raltegravir (RAL) which was demonstrated to have non-inferior efficacy relative to a regimen of LPV/r with nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) (Control) in primary analysis at 48 weeks. Design: Open label, centrally randomised trial. Setting: Recruitment was from 37 primary and secondary care sites from Africa, Asia, Australia, Europe and Latin America. Subjects: 541 HIV-1 infected adults virologically failing first-line non-NRTI + 2N(t)RTI, with no previous exposure to protease inhibitors or integrase strand transfer inhibitors were analysed, 425 completed 96 weeks follow up on randomised therapy. Intervention: Randomisation was 1:1 to Control or RAL. Main outcome measures: Differences between the proportion of participants with plasma HIV-1 RNA (VL) <200 copies/mL by intention to treat were compared with a non-inferiority margin of -12%. Differences in biochemical, haematological and metabolic changes were assessed using T-tests. Results: VL <200 copies/mL at 96 weeks was: RAL 80.4%, Control 76.0%(difference: 4.4 [95%CI -2.6, 11.3]) andmet non-inferiority criteria. The RAL arm had a significantly higher mean change (difference Control-RAL; 95%CI) in haemoglobin (-2.9; -5.7, -1.1), total lymphocytes (-0.2; -0.3, -0.0), total cholesterol (-0.5; -0.8, -0.3), HDL cholesterol (-0.1; -0.1, -0.0) and LDL cholesterol (-0.3; -0.5, -0.2). Conclusion: At 96 weeks, both RAL and Control maintained efficacy greater than 75% and continued to demonstrate similar safety profiles. These results support the use of a combination LPV/r and RAL regimen as an option following failure of 1st line NNRTI + 2N(t)RTIs. Trial Registration: ClinicalTrials.gov NCT00931463.

Original languageEnglish
Article numbere0118228
Pages (from-to)1-13
Number of pages13
JournalPLoS ONE
Volume10
Issue number2
DOIs
Publication statusPublished - 27 Feb 2015
Externally publishedYes

Bibliographical note

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.

Erratum can be found at PLoS ONE volume 10(10), article e0140623, https://doi.org/10.1371/journal.pone.0140623

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