title: Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  The National Health Security Office and Kirby Institute for Infection and Immunity in Society.
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand.
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.affiliation: Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sasisopin
authors.initials: S
authors.lastname: Kiertiburanakul
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.affiliation: Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
authors.affiliation: Prapokklao Hospital, Amphur Muang, Chanthaburi, Thailand.
authors.forename: Malee
authors.initials: M
authors.lastname: Techapornroong
authors.affiliation: Khon Kaen Hospital, Mueang Khon Kaen, Khon Kaen, Thailand.
authors.forename: Niramon
authors.initials: N
authors.lastname: Leerattanapetch
authors.affiliation: Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand.
authors.forename: Pacharee
authors.initials: P
authors.lastname: Kantipong
authors.affiliation: Chonburi Hospital, Baan Suan Muang, Chonburi, Thailand.
authors.forename: Chureeratana
authors.initials: C
authors.lastname: Bowonwatanuwong
authors.affiliation: Rayong Hospital, Mueang Rayong, Rayong, Thailand.
authors.forename: Sukit
authors.initials: S
authors.lastname: Banchongkit
authors.affiliation: Sanpatong Hospital, San Pa Tong, Chiang Mai, Thailand.
authors.forename: Virat
authors.initials: V
authors.lastname: Klinbuayaem
authors.affiliation: Pranangklao Hospital, Nonthaburi, Thailand.
authors.forename: Sripetcharat
authors.initials: S
authors.lastname: Mekviwattanawong
authors.affiliation: Nakhon Phatom Hospital, Mueang Nakhon Pathom, Nakhon Phatom, Thailand.
authors.forename: Sireethorn
authors.initials: S
authors.lastname: Nimitvilai
authors.affiliation: Taksin Hospital, Khlong San, Bangkok, Thailand.
authors.forename: Supunnee
authors.initials: S
authors.lastname: Jirajariyavej
authors.affiliation: Bamrasnaradura Infectious Disease Institute, Mueang Nonthaburi, Nonthaburi, Thailand.
authors.forename: Wisit
authors.initials: W
authors.lastname: Prasithsirikul
authors.affiliation: Faculty of Medicine, Vajira Hospital, University of Bangkok Metropolitan Administration, Wachira Phayaban, Dusit, Bangkok, Thailand.
authors.forename: Warangkana
authors.initials: W
authors.lastname: Munsakul
authors.affiliation: The National Health Security Office, Nonthaburi, Thailand.
authors.forename: Sorakij
authors.initials: S
authors.lastname: Bhakeecheep
authors.affiliation: The National Health Security Office, Nonthaburi, Thailand.
authors.forename: Suchada
authors.initials: S
authors.lastname: Chaivooth
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand.
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.affiliation: Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand.
authors.forename: Tanakorn
authors.initials: T
authors.lastname: Apornpong
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand; Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia; Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.affiliation: Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand; Department of Medicine, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, Thailand. Electronic address: kiat.r@chula.ac.th.
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D000293:Adolescent; D000328:Adult; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D011247:Pregnancy; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D013785:Thailand / Q000453:epidemiology; D019562:Viral Load; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D000069446:Atazanavir Sulfate; D019438:Ritonavir