PMID- 25926858
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150430
LR  - 20190108
IS  - 1742-6405 (Print)
IS  - 1742-6405 (Electronic)
IS  - 1742-6405 (Linking)
VI  - 11
DP  - 2014
TI  - Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase 
      IIIb, open-label single-arm trial.
PG  - 39
LID - 10.1186/1742-6405-11-39 [doi]
LID - 39
AB  - BACKGROUND: Cobicistat is an alternative pharmacoenhancer to ritonavir. In 
      healthy volunteers, darunavir exposure was comparable when darunavir 800 mg once 
      daily was co-administered with cobicistat 150 mg once daily (as single agents or 
      a fixed-dose combination) vs. with ritonavir 100 mg once daily. METHODS: This 
      48-week, Phase IIIb, single-arm, US multicenter study (NCT01440569) evaluated 
      safety, efficacy and pharmacokinetics of darunavir/cobicistat 800/150 mg once 
      daily (as single agents) plus two investigator-selected nucleoside/tide reverse 
      transcriptase inhibitors (N[t]RTIs) in HIV-1-infected adults. Patients had no 
      darunavir resistance-associated mutations (RAMs), plasma viral load (VL) >/=1000 
      HIV-1 RNA copies/ml, eGFR >/=80 ml/min and genotypic sensitivity to the two 
      N[t]RTIs. The primary endpoint was any treatment-emergent grade 3 or 4 adverse 
      events (AEs) through Week 24. RESULTS: The majority of the 313 intent-to-treat 
      patients were treatment-naive (295/313; 94%), male (89%), White (60%) and 
      received a tenofovir-based regimen (99%). Median baseline VL and CD4(+) count 
      overall were 4.8 log10 HIV-1 RNA copies/ml and 361 cells/mm(3), respectively. 
      Overall, 86% of patients (268/313) completed the study. The majority of 
      discontinuations were for AEs (15/313; 5%). The incidence of treatment-emergent 
      grade 3 or 4 AEs regardless of causality was 6% through Week 24 and 8% through 
      Week 48. Most common AEs through Week 48 were diarrhea (27%) and nausea (23%), 
      which were grade 1 or 2 in severity. Week 48 virologic response rates (% with VL 
      <50 HIV-1 RNA copies/ml; Snapshot analysis) were 81% overall and 83% in 
      treatment-naive patients; median increases in CD4(+) count at 48 weeks were 167 
      and 169 cells/mm(3), respectively. Of 15/313 patients who met the criteria for 
      resistance analysis, one developed a darunavir RAM as a mixture with wild-type 
      (I84I/V), without phenotypic resistance to darunavir. The mean population 
      pharmacokinetic-derived darunavir areas under the plasma concentration-time curve 
      were 102,000 overall and 100,620 ng*h/ml in treatment-naive patients. No 
      clinically relevant relationships were seen between darunavir exposure and 
      virologic response, AEs or laboratory parameters. CONCLUSION: 
      Darunavir/cobicistat 800/150 mg once daily was generally well tolerated through 
      Week 48, with no new safety concerns. Pharmacokinetics, virologic and immunologic 
      responses for darunavir/cobicistat were similar to previous data for 
      darunavir/ritonavir 800/100 mg once daily.
FAU - Tashima, Karen
AU  - Tashima K
AD  - The Miriam Hospital, Alpert Medical School of Brown University, 164 Summit 
      Avenue, Providence, RI 02906 USA.
FAU - Crofoot, Gordon
AU  - Crofoot G
AD  - Gordon Crofoot Research, Houston, TX USA.
FAU - Tomaka, Frank L
AU  - Tomaka FL
AD  - Janssen Research & Development LLC, Titusville, NJ USA.
FAU - Kakuda, Thomas N
AU  - Kakuda TN
AD  - Janssen Research & Development LLC, Titusville, NJ USA.
FAU - Brochot, Anne
AU  - Brochot A
AD  - Janssen Research & Development, Beerse, Belgium.
FAU - Van de Casteele, Tom
AU  - Van de Casteele T
AD  - Janssen Infectious Diseases BVBA, Beerse, Belgium.
FAU - Opsomer, Magda
AU  - Opsomer M
AD  - Janssen Infectious Diseases BVBA, Beerse, Belgium.
FAU - Garner, William
AU  - Garner W
AD  - Gilead Sciences, Foster City, CA USA.
FAU - Margot, Nicolas
AU  - Margot N
AD  - Gilead Sciences, Foster City, CA USA.
FAU - Custodio, Joseph M
AU  - Custodio JM
AD  - Gilead Sciences, Foster City, CA USA.
FAU - Fordyce, Marshall W
AU  - Fordyce MW
AD  - Gilead Sciences, Foster City, CA USA.
FAU - Szwarcberg, Javier
AU  - Szwarcberg J
AD  - Gilead Sciences, Foster City, CA USA.
LA  - eng
PT  - Journal Article
DEP - 20141201
PL  - England
TA  - AIDS Res Ther
JT  - AIDS research and therapy
JID - 101237921
PMC - PMC4413526
OTO - NOTNLM
OT  - Cobicistat
OT  - Darunavir
OT  - Efficacy
OT  - Pharmacokinetics
OT  - Safety
OT  - Virology
EDAT- 2014/01/01 00:00
MHDA- 2014/01/01 00:01
PMCR- 2014/12/01
CRDT- 2015/05/01 06:00
PHST- 2014/07/28 00:00 [received]
PHST- 2014/11/09 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2014/01/01 00:00 [pubmed]
PHST- 2014/01/01 00:01 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 333 [pii]
AID - 10.1186/1742-6405-11-39 [doi]
PST - epublish
SO  - AIDS Res Ther. 2014 Dec 1;11:39. doi: 10.1186/1742-6405-11-39. eCollection 2014.