Publication:
Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial

Issued Date

2016-08-01

Resource Type

Article

ISSN

23523018

DOI

10.1016/S2352-3018(16)30010-8

Other identifier(s)

2-s2.0-84969667316

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet HIV. Vol.3, No.8 (2016), e343-e350

Suggested Citation

Torsak Bunupuradah, Sasisopin Kiertiburanakul, Anchalee Avihingsanon, Ploenchan Chetchotisakd, Malee Techapornroong, Niramon Leerattanapetch, Pacharee Kantipong, Chureeratana Bowonwatanuwong, Sukit Banchongkit, Virat Klinbuayaem, Sripetcharat Mekviwattanawong, Sireethorn Nimitvilai, Supunnee Jirajariyavej, Wisit Prasithsirikul, Warangkana Munsakul, Sorakij Bhakeecheep, Suchada Chaivooth, Praphan Phanuphak, David A. Cooper, Tanakorn Apornpong, Stephen J. Kerr, Sean Emery, Kiat Ruxrungtham Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial. The Lancet HIV. Vol.3, No.8 (2016), e343-e350. doi:10.1016/S2352-3018(16)30010-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/40769

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Title

Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial

Author(s)

Torsak Bunupuradah
 Sasisopin Kiertiburanakul
 Anchalee Avihingsanon
 Ploenchan Chetchotisakd
 Malee Techapornroong
 Niramon Leerattanapetch
 Pacharee Kantipong
 Chureeratana Bowonwatanuwong
 Sukit Banchongkit
 Virat Klinbuayaem
 Sripetcharat Mekviwattanawong
 Sireethorn Nimitvilai
 Supunnee Jirajariyavej
 Wisit Prasithsirikul
 Warangkana Munsakul
 Sorakij Bhakeecheep
 Suchada Chaivooth
 Praphan Phanuphak
 David A. Cooper
 Tanakorn Apornpong
 Stephen J. Kerr
 Sean Emery
 Kiat Ruxrungtham

Other Contributor(s)

The HIV Netherlands Australia Thailand Research Collaboration
 Mahidol University
 Khon Kaen University
 Prapokklao Hospital
 Khon Kaen Regional Hospital
 Chiangrai Prachanukroh Hospital
 Chonburi Regional Hospital
 Rayong Hospital
 Sanpatong Hospital
 Pranangklao Hospital
 Nakhon Phatom Hospital
 Taksin Hospital
 Bamrasnaradura Infectious Disease Institute
 Bangkok Metropolitan Administration
 National Health Security Office
 University of New South Wales (UNSW) Australia
 Academic Medical Centre, University of Amsterdam
 Chulalongkorn University

Abstract

© 2016 Elsevier Ltd Background Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV. Methods In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was −10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223. Findings Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI −2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p<0·0001). Interpretation A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors. Funding The National Health Security Office and Kirby Institute for Infection and Immunity in Society.

Keyword(s)

Immunology and Microbiology
 Medicine

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URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/40769

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Scopus 2016-2017