PMID- 33528318
OWN - NLM
STAT- MEDLINE
DCOM- 20220225
LR  - 20220531
IS  - 2578-7470 (Electronic)
IS  - 2578-7470 (Linking)
VI  - 21
IP  - 6
DP  - 2020 Dec
TI  - Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials 
      evaluating the efficacy and safety of the once daily 
      darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 
      single-tablet regimen in antiretroviral treatment (ART)-naive and -experienced, 
      virologically-suppressed adults living with HIV-1.
PG  - 151-167
LID - 10.1080/25787489.2020.1844520 [doi]
AB  - BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 
      800/150/200/10 mg was investigated in AMBER (treatment-naive adults; NCT02431247) 
      and EMERALD (treatment-experienced, virologically-suppressed adults; 
      NCT02269917). OBJECTIVE: To describe a Week 96 pre-planned subgroup analysis of 
      D/C/F/TAF arms by demographic characteristics (age </=/>50 years, gender, 
      black/non-black race), and baseline clinical characteristics (AMBER: viral load 
      [VL], CD4(+) count, WHO clinical stage, HIV-1 subtype and antiretroviral 
      resistance; EMERALD: prior virologic failure [VF], antiretroviral experience, 
      screening boosted protease inhibitor [PI], and boosting agent). METHODS: Patients 
      in D/C/F/TAF and control arms could continue on/switch to D/C/F/TAF in a 
      single-arm, open-label extension phase after Week 48 until Week 96. Efficacy 
      endpoints were percentage cumulative confirmed VL >/=50 copies/mL (virologic 
      rebound; EMERALD), and VL <50 (virologic response), or >/=50 copies/mL (VF) (FDA 
      snapshot; both trials). RESULTS: D/C/F/TAF demonstrated high Week 96 virologic 
      responses (AMBER: 85% [308/362]; EMERALD: 91% [692/763]) and low VF rates (AMBER: 
      6% [20/362]; EMERALD: 1% [9/763]). In EMERALD, D/C/F/TAF showed low virologic 
      rebound cumulative through Week 96 (3% [24/763]). Results were consistent across 
      subgroups, including prior antiretroviral experience in EMERALD. No darunavir, 
      primary PI, or tenofovir resistance-associated mutations were observed 
      post-baseline. Study-drug-related serious adverse events (AEs) and AE-related 
      discontinuations were <1% and 2%, respectively (both D/C/F/TAF arms), and similar 
      across subgroups. eGFR(cyst) and bone mineral density improved or were stable and 
      lipids increased through Week 96 across demographic subgroups, with small changes 
      in total-cholesterol/HDL-cholesterol ratio. CONCLUSIONS: D/C/F/TAF was effective 
      with a high barrier to resistance and bone/renal safety benefits, regardless of 
      demographic or clinical characteristics for treatment-naive and 
      treatment-experienced, virologically-suppressed adults.
FAU - Huhn, Gregory D
AU  - Huhn GD
AD  - Ruth M. Rothstein CORE Center, Chicago, IL, USA.
FAU - Wilkin, Aimee
AU  - Wilkin A
AD  - Section on Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, 
      NC, USA.
FAU - Mussini, Cristina
AU  - Mussini C
AD  - Department of Infectious Diseases, University of Modena and Reggio Emilia, 
      Modena, Italy.
FAU - Spinner, Christoph D
AU  - Spinner CD
AUID- ORCID: 0000-0002-3875-5367
AD  - School of Medicine, Technical University of Munich, Munich, Germany.
FAU - Jezorwski, John
AU  - Jezorwski J
AD  - Janssen Research and Development LLC, Pennington, NJ, USA.
FAU - El Ghazi, Mohsine
AU  - El Ghazi M
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Van Landuyt, Erika
AU  - Van Landuyt E
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Lathouwers, Erkki
AU  - Lathouwers E
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Brown, Kimberley
AU  - Brown K
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Baugh, Bryan
AU  - Baugh B
AD  - Janssen Research and Development LLC, Raritan, NJ, USA.
CN  - AMBER and EMERALD study groups
LA  - eng
SI  - ClinicalTrials.gov/NCT02269917
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210202
PL  - England
TA  - HIV Res Clin Pract
JT  - HIV research & clinical practice
JID - 101738312
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Tablets)
RN  - 99YXE507IL (Tenofovir)
RN  - EL9943AG5J (tenofovir alafenamide)
RN  - G70B4ETF4S (Emtricitabine)
RN  - LW2E03M5PG (Cobicistat)
RN  - OF5P57N2ZX (Alanine)
RN  - YO603Y8113 (Darunavir)
SB  - IM
MH  - Adult
MH  - Alanine
MH  - *Anti-HIV Agents/adverse effects
MH  - Cobicistat
MH  - Darunavir/adverse effects
MH  - Emtricitabine
MH  - *HIV Infections/drug therapy
MH  - *HIV-1/genetics
MH  - Humans
MH  - Middle Aged
MH  - Tablets/pharmacology/therapeutic use
MH  - Tenofovir/analogs & derivatives
OTO - NOTNLM
OT  - D/C/F/TAF
OT  - HIV-1
OT  - Phase III
OT  - darunavir
OT  - single-tablet regimen
OT  - subgroup analysis
OT  - tenofovir alafenamide
EDAT- 2021/02/03 06:00
MHDA- 2022/02/26 06:00
CRDT- 2021/02/02 12:11
PHST- 2021/02/03 06:00 [pubmed]
PHST- 2022/02/26 06:00 [medline]
PHST- 2021/02/02 12:11 [entrez]
AID - 10.1080/25787489.2020.1844520 [doi]
PST - ppublish
SO  - HIV Res Clin Pract. 2020 Dec;21(6):151-167. doi: 10.1080/25787489.2020.1844520. 
      Epub 2021 Feb 2.