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Randomized Controlled Trial
. 2015 Feb 27;10(2):e0118228.
doi: 10.1371/journal.pone.0118228. eCollection 2015.

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  1 , Mark A Boyd  1 , Nagalingeswaran Kumarasamy  2 , Cecilia L Moore  1 , Marcello H Losso  3 , Chidi A Nwizu  4 , Lerato Mohapi  5 , Stephen J Kerr  6 , Annette H Sohn  7 , Hedy Teppler  8 , Boris Renjifo  9 , Jean-Michel Molina  10 , Sean Emery  1 , David A Cooper  1
Affiliations
Randomized Controlled Trial

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 et al. PLoS One. .

Erratum in

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]) and met 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.

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Conflict of interest statement

Competing Interests: The authors have the following interests. Merck and AbbVie partly funded the study. The sponsors participated in the study design, data collection, data analysis, data interpretation, and review and approval of the report and supplied the study drug. Hedy Teppler is employed by Merck Research Laboratories, and owns stocks and shares in the company. Boris Renjifo is employed by Abbvie and may hold Abbott or AbbVie stock or options. Raltegravir is produced by Merck & Co. and Ritonavir by AbbVie. MB has received research grant support and honoraria for serving on advisory boards and educational presentations from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, and Merck. CN has served as a speaker and received honoraria from AbbVie. ML has received research grants and unrestricted educational grants from Abbott and Merck in the past 10 years. LM received travel assistance to a conference from Pfizer Pharmaceutical in 2008. J-MM has received research grants from Merck and Gilead and participated in advisory boards on antiretroviral drugs organised by Merck, Bristol-Myers Squibb, ViiV, Gilead Sciences, and Janssen Pharmaceuticals. AS is on ViiV Health's paediatric advisory board. SE has received research grant support from Abbvie, Gilead Sciences, Merck Research Laboratories, Pfizer, and ViiV Healthcare. DAC has participated on advisory boards for Merck Sharp and Dohme and AbbVie. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. Sean Emery and Janaki Amin are a PLOS ONE Editorial Board members. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria.

Figures

Fig 1
Fig 1. Participant disposition over 96 weeks.
Fig 2
Fig 2. Virologic response at Week 96, by randomised arm, study population and screening strata.
RAL = lopinavir/ritonavir+raltegravir Control = lopinavir/ritonavir+2/3 nucleoside/nucleotide reverse transcriptase inhibitors. *grey circle = screening plasma viral load strata, P interaction = 0.81, bars are 95%confidence intervals (CI).
Fig 3
Fig 3. Mean change from baseline in CD4+ T cells/mm3 over 96 weeks by randomised arm.
RAL = lopinavir/ritonavir+raltegravir Control = lopinavir/ritonavir+2/3 nucleoside/nucleotide reverse transcriptase inhibitors. (Control- - - RAL ---, bars indicate standard deviation).
Fig 4
Fig 4. Absolute mean cholesterol fractions and ratio over 96 weeks by randomised arm.
(A) total cholesterol, (B) high density lipoprotein (HDL) cholesterol, (C) low density lipoprotein (LDL) cholesterol, (D) Total:HDL cholesterol ratio. RAL = lopinavir/ritonavir+raltegravir Control = lopinavir/ritonavir+2/3 nucleoside/nucleotide reverse transcriptase inhibitors. (Control - - - RAL ---, bars indicate standard deviation).
See this image and copyright information in PMC

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