PMID- 29498742
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20180717
IS  - 1121-7138 (Print)
IS  - 1121-7138 (Linking)
VI  - 41
IP  - 2
DP  - 2018 Apr
TI  - Potential associations between atazanavir exposure and clinical outcome: a 
      pharmacokinetic sub-study from the MODAt randomized trial.
PG  - 106-111
AB  - The 96-week results of the Monotherapy Once a Day with Atazanavir/r (MODAt) study 
      [NCT01511809] showed an inferior virological efficacy of atazanavir 
      (ATV)/ritonavir monotherapy versus triple therapy, which was promptly retrieved 
      by the reintroduction of nucleoside/nucleotide inhibitors of reverse 
      transcriptase [N(n)RTIs]. We aimed to identify potential relationships between 
      ATV exposure and clinical outcome in HIV-1 subjects treated with ATV/ritonavir 
      monotherapy [ATV/r 300/100 mg] versus ATV/ritonavir triple therapy [ATV/r 300/100 
      mg+2NRTIs]. A chromatographic method coupled with tandem mass spectrometry was 
      applied to analyze ATV plasma concentrations in a pharmacokinetic sub-study from 
      the MODAt trial. Mixed linear models were used to examine the ATV plasma 
      concentration trend during follow-up and to assess the association between ATV 
      plasma concentrations trajectories with the study arm or the occurrence of 
      treatment failure or drugrelated adverse events or the grading of baseline total 
      bilirubin (<3 vs >/=3). The analyses were performed using SAS Software, release 9.4 
      (SAS Institute, Cary, NC, USA). Overall, ATV plasma Ctrough concentration did not 
      vary during follow-up (slope: +0.75 ng/mL/week, 95%CI: -0.97 to 2.47, p=0.387); 
      trajectories did not differ between study arms (p=0.527). The unadjusted 
      model-based means (95%CI) of ATV Ctrough during follow-up were 835 (95%CI: 
      657-1012) ng/ml in the ATV/r monotherapy arm as compared to 911 (95%CI: 740-1082) 
      ng/mL in the ATV/r triple therapy arm (p=0.621). Mean ATV Ctrough was similar in 
      subjects with or without adverse events (AEs). Subjects treated with ATV/r 
      monotherapy showed significantly higher ATV concentrations as compared to 
      subjects without adverse events or treated with ATV/r triple therapy. ATV 
      concentrations were associated with the grading of baseline total bilirubin and 
      the occurrence of drug-related AEs but not with HCV infection. Our findings 
      showed a lack of association between ATV concentrations and treatment failure 
      both in ATV/r monotherapy and triple therapy. Conversely, these data emphasized 
      that ATV concentrations are associated with the development of side-effects in 
      both subjects treated with ATV/r monotherapy and subjects treated with ATV/r 
      triple therapy.
FAU - Colella, Elisa
AU  - Colella E
AD  - Infectious Diseases Unit, Department of Biomedical and Clinical Sciences 'Luigi 
      Sacco', Universita degli Studi di Milano, Milan, Italy.
FAU - Cattaneo, Dario
AU  - Cattaneo D
AD  - Clinical Pharmacology Unit, Luigi Sacco University Hospital, Milan, Italy.
FAU - Galli, Laura
AU  - Galli L
AD  - Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, 
      Italy.
FAU - Baldelli, Sara
AU  - Baldelli S
AD  - Clinical Pharmacology Unit, Luigi Sacco University Hospital, Milan, Italy.
FAU - Clementi, Emilio
AU  - Clementi E
AD  - Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences 
      'Luigi Sacco' University Hospital, Consiglio Nazionale delle Ricerche Institute 
      of Neuroscience, Universita degli Studi d.
AD  - E. Medea Scientific Institute, Bosisio Parini, Italy.
FAU - Galli, Massimo
AU  - Galli M
AD  - Infectious Diseases Unit, Department of Biomedical and Clinical Sciences 'Luigi 
      Sacco', Universita degli Studi di Milano, Milan, Italy.
FAU - Lazzarin, Adriano
AU  - Lazzarin A
AD  - Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, 
      Italy.
FAU - Castagna, Antonella
AU  - Castagna A
AD  - Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, 
      Italy.
FAU - Rusconi, Stefano
AU  - Rusconi S
AD  - Infectious Diseases Unit, Department of Biomedical and Clinical Sciences 'Luigi 
      Sacco', Universita degli Studi di Milano, Milan, Italy.
FAU - Spagnuolo, Vincenzo
AU  - Spagnuolo V
AD  - Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, 
      Italy.
LA  - eng
PT  - Journal Article
DEP - 20180302
PL  - Italy
TA  - New Microbiol
JT  - The new microbiologica
JID - 9516291
RN  - 0 (HIV Protease Inhibitors)
RN  - 4MT4VIE29P (Atazanavir Sulfate)
SB  - IM
MH  - Adult
MH  - Antiretroviral Therapy, Highly Active
MH  - Atazanavir Sulfate/*pharmacokinetics/*therapeutic use
MH  - Female
MH  - HIV Infections/blood/*drug therapy
MH  - HIV Protease Inhibitors/administration & 
      dosage/blood/*pharmacokinetics/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Treatment Failure
OTO - NOTNLM
OT  - Atazanavir
OT  - Bilirubin
OT  - HCV
OT  - HIV-1
OT  - Monotherapy
OT  - Pharmacokinetics
EDAT- 2018/03/03 06:00
MHDA- 2018/07/18 06:00
CRDT- 2018/03/03 06:00
PHST- 2018/05/28 00:00 [received]
PHST- 2018/05/28 00:00 [accepted]
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
PHST- 2018/03/03 06:00 [entrez]
AID - 496N006 [pii]
PST - ppublish
SO  - New Microbiol. 2018 Apr;41(2):106-111. Epub 2018 Mar 2.