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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Raltegravir once daily or twice daily in previously untreated patients with HIV-1: A randomised, active-controlled, phase 3 non-inferiority trial
The Lancet Infectious Diseases, Volume 11, No. 12, Year 2011
Notification
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Description
Background: Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to compare these dosing schedules. Methods: In our international, double-blind, randomised, phase 3 non-inferiority study, we enrolled antiretroviral-naive patients with HIV RNA loads of more than 5000 copies per mL and no baseline resistance to tenofovir or emtricitabine at 83 centres worldwide. We randomly allocated patients (1:1) by use of a computer-generated sequence to receive raltegravir once daily (two 400 mg tablets taken together every 24 h), or twice daily (one 400 mg tablet every 12 h), both in combination with once-daily co-formulated tenofovir 300 mg plus emtricitabine 150 mg. The primary outcome was virological response at 48 weeks (viral RNA loads <50 copies per mL) in patients who received at least one dose of study drug, counting non-completers as failure. We assessed non-inferiority in terms of the proportion of patients in both treatment groups who achieved the primary outcome, with a non-inferiority margin of -10%. This study is registered with ClinicalTrials.gov, number NCT00745823. Findings: From Oct 15, 2008, to Nov 2, 2009, we randomly allocated 775 patients, of whom 382 (99%) of 386 patients in the once-daily group and 388 (99%) of 389 in the twice-daily group received at least one dose of study drug. At baseline, 304 (39%) of 770 treated patients had viral loads of more than 100 000 copies per mL and 188 (24%) had CD4 cell counts of fewer than 200 cells per μL. 318 (83%) of 382 patients in the once-daily group had virological response compared with 343 (89%) of 386 in the twice-daily group (difference -5·7%, 95% CI -10·7 to -0·83; p=0·044). Serious adverse events were reported in 26 (7%) of 382 once-daily recipients and 40 (10%) of 388 twice-daily recipients, and adverse events leading to discontinuation occurred in four (1%) patients in each group. Interpretation: Despite high response rates with both regimens, once-daily raltegravir cannot be recommended in place of twice-daily dosing. Funding: Merck. © 2011 Elsevier Ltd.
Authors & Co-Authors
Eron, Joseph J.
Unknown Affiliation
Rockstroh, Jürgen Kurt
Unknown Affiliation
Reynès, Jacques M.
Unknown Affiliation
Andrade-Villanueva, Jaime
Unknown Affiliation
Ramalho-Madruga, José Valdez
Unknown Affiliation
Bekker, Linda-Gail Gail
Unknown Affiliation
Young, Benjamin
Unknown Affiliation
Katlama, Christine
Unknown Affiliation
Gatell-Artigas, Jose Maria
Unknown Affiliation
Arribas, Jose R.
Unknown Affiliation
Nelson, Mark Richard
Unknown Affiliation
Campbell, Havilland
Unknown Affiliation
Zhao, Jing
Unknown Affiliation
Rodgers, Anthony J.
Unknown Affiliation
Rizk, Matthew L.
Unknown Affiliation
Wenning, Larissa A.
Unknown Affiliation
Miller, Michael Dean
Unknown Affiliation
Hazuda, Daria
Unknown Affiliation
DiNubile, Mark J.
Unknown Affiliation
Leavitt, Randi Y.
Unknown Affiliation
Isaacs, Robin
Unknown Affiliation
Robertson, Michael N.
Unknown Affiliation
Sklar, Peter A.
Unknown Affiliation
Nguyen, Bach Yen T.
Unknown Affiliation
Statistics
Citations: 207
Authors: 24
Affiliations: 13
Identifiers
Doi:
10.1016/S1473-3099(11)70196-7
ISSN:
14733099
e-ISSN:
14744457
Research Areas
Disability
Infectious Diseases