PMID- 25433666
OWN - NLM
STAT- MEDLINE
DCOM- 20150129
LR  - 20151119
IS  - 1528-4336 (Print)
IS  - 1528-4336 (Linking)
VI  - 15
IP  - 6
DP  - 2014 Nov-Dec
TI  - Cobicistat-boosted protease inhibitors in HIV-infected patients with mild to 
      moderate renal impairment.
PG  - 269-73
LID - 10.1310/hct1506-269 [doi]
AB  - BACKGROUND: Cobicistat (COBI) is a pharmacoenhancer that optimizes systemic 
      exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir 
      (DRV). OBJECTIVE: To evaluate the efficacy and safety of switching ritonavir 
      (RTV) to COBI in patients with creatinine clearance (CrCl) 50 to 89 mL/min who 
      are virologically suppressed on a stable regimen containing ritonavir 
      (RTV)-boosted ATV or DRV. Other components of the regimen remained unchanged. 
      METHODS: A phase 3, non-comparative, open-label clinical trial. RESULTS: 
      Seventy-three patients were enrolled. At week 48, 82% maintained virologic 
      suppression. No emergent resistance developed. Serious adverse events (AEs) 
      occurred in 7%, and study drug discontinuation due to AEs occurred in 10% (7 
      patients). There were 2 renal discontinuations and no cases of proximal renal 
      tubulopathy. Small reductions in CrCl (median [IQR]) were observed as early as 
      week 2, after which they were nonprogressive through week 48 (-3.8 [-9 to 0.8]). 
      Changes in CrCl by baseline CrCl (< 70 vs >/= 70) were -1.1 [-6.5 to 6.3] versus 
      -6.6 [-12.4 to -0.7], respectively. CONCLUSIONS: In HIV-1-infected patients with 
      CrCl 50 to 89 mL/min switching from RTV to COBI, COBI-boosted PIs in combination 
      with 2 nucleos(t)ide reverse transcriptase inhibitors were well-tolerated and 
      effective in maintaining virologic suppression. The renal safety profile of COBI 
      in this study was consistent with the long-term data in patients without renal 
      impairment from the phase 3 studies of COBI-containing regimens.
FAU - McDonald, Cheryl K
AU  - McDonald CK
AD  - Tarrant County Infectious Disease, Fort Worth, Texas.
FAU - Martorell, Claudia
AU  - Martorell C
AD  - The Research Institute, Springfield, Massachusetts.
FAU - Ramgopal, Moti
AU  - Ramgopal M
AD  - Midway Immunology and Research Center, Fort Pierce, Florida.
FAU - Laplante, Francois
AU  - Laplante F
AD  - Clinique Medicale du Quartier Latin, Montreal, Canada.
FAU - Fisher, Martin
AU  - Fisher M
AD  - Brighton and Sussex Medical School, Brighton, UK.
FAU - Post, Frank A
AU  - Post FA
AD  - Kings College Hospital, London, UK.
FAU - Liu, Yapei
AU  - Liu Y
AD  - Gilead Sciences, Foster City, California.
FAU - Curley, Joanne
AU  - Curley J
AD  - Gilead Sciences, Foster City, California.
FAU - Abram, Michael E
AU  - Abram ME
AD  - Gilead Sciences, Foster City, California.
FAU - Custodio, Joseph
AU  - Custodio J
AD  - Gilead Sciences, Foster City, California.
FAU - Graham, Hiba
AU  - Graham H
AD  - Gilead Sciences, Foster City, California.
FAU - Rhee, Martin S
AU  - Rhee MS
AD  - Gilead Sciences, Foster City, California.
FAU - Szwarcberg, Javier
AU  - Szwarcberg J
AD  - Gilead Sciences, Foster City, California.
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - HIV Clin Trials
JT  - HIV clinical trials
JID - 100936377
RN  - 0 (Carbamates)
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Thiazoles)
RN  - LW2E03M5PG (Cobicistat)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carbamates/adverse effects/metabolism/*therapeutic use
MH  - Cobicistat
MH  - Female
MH  - HIV Infections/complications/*drug therapy
MH  - HIV Protease Inhibitors/adverse effects/metabolism/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Renal Insufficiency/complications/*metabolism
MH  - Thiazoles/adverse effects/metabolism/*therapeutic use
OTO - NOTNLM
OT  - HIV clinical trials
OT  - cobicistat
OT  - renal impairment
EDAT- 2014/12/01 06:00
MHDA- 2015/01/30 06:00
CRDT- 2014/12/01 06:00
PHST- 2014/12/01 06:00 [entrez]
PHST- 2014/12/01 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
AID - X13H116025742029 [pii]
AID - 10.1310/hct1506-269 [doi]
PST - ppublish
SO  - HIV Clin Trials. 2014 Nov-Dec;15(6):269-73. doi: 10.1310/hct1506-269.