title: Treatment response to unboosted atazanavir in combination with tenofovir disoproxil fumarate and lamivudine in human immunodeficiency virus-1-infected patients who have achieved virological suppression: A therapeutic drug monitoring and pharmacogenetic study.
abstract: OBJECTIVE
  Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infected patients is rarely investigated.
  
  
  METHODS
  Consecutive patients with plasma human immunodeficiency virus RNA load < 200 copies/mL switching to unboosted atazanavir plus zidovudine-lamivudine (coformulated), abacavir-lamivudine (coformulated), or TDF/lamivudine > 3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load ≥ 200 copies/mL within 96 weeks.
  
  
  RESULTS
  During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (p < 0.01). After a median follow-up duration of 96.0 weeks, treatment failure occurred in 19 (14.9%) and 34 (18.3%) patients in the TDF group and non-TDF group, respectively (p = 0.60). Low-level viremia (40-200 copies/mL) before switch (adjusted hazard ratio, 2.12; 95% confidence interval, 1.12-4.01) and without therapeutic drug monitoring (adjusted hazard ratio, 2.08; 95% confidence interval, 1.16-3.73) were risk factors for treatment failure.
  
  
  CONCLUSIONS
  Switch to unboosted atazanavir with TDF/lamivudine achieves a similar treatment response to that with two other nucleoside reverse-transcriptase inhibitors in patients achieving virological suppression with the guidance of therapeutic drug monitoring.
authors: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors: Mao-Song
authors: MS
authors: Tsai
authors: Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Sui-Yuan
authors: SY
authors: Chang
authors: Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors: Shu-Wen
authors: SW
authors: Lin
authors: Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan.
authors: Ching-Hua
authors: CH
authors: Kuo
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Hsin-Yun
authors: HY
authors: Sun
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Bin-Ru
authors: BR
authors: Wu
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Sue-Yo
authors: SY
authors: Tang
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Wen-Chun
authors: WC
authors: Liu
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Yi-Ching
authors: YC
authors: Su
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan. Electronic address: hcc0401@ntu.edu.tw.
authors: Chien-Ching
authors: CC
authors: Hung
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Shan-Chwen
authors: SC
authors: Chang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000069446:Atazanavir Sulfate / Q000097:blood / Q000627:therapeutic use*; D004338:Drug Combinations; D016903:Drug Monitoring; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000074435:Peroxisome-Targeting Signal 1 Receptor / Q000235:genetics; D000071185:Pharmacogenomic Testing; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000069446:Atazanavir Sulfate; D004338:Drug Combinations; D014453:Glucuronosyltransferase; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000099148:UGT1A1 Enzyme; C513055:ABCB1 protein, human; C000614264:PEX5 protein, human
keywords: antiretroviral agent; combination antiretroviral therapy; drug–drug interaction; nucleoside reverse-transcriptase inhibitor; protease inhibitor