PMID- 31355775
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20201209
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 24
IP  - 6
DP  - 2019
TI  - Doravirine dose selection and 96-week safety and efficacy versus efavirenz in 
      antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial.
PG  - 425-435
LID - 10.3851/IMP3323 [doi]
AB  - BACKGROUND: The safety and efficacy of doravirine were compared with that of 
      efavirenz as initial treatment of adults living with HIV-1 infection 
      (NCT01632345). METHODS: A Phase IIb double-blind trial with participants 
      stratified by screening HIV-1 RNA (</= or >100,000 copies/ml) and randomized 
      1:1:1:1:1 to receive once-daily doravirine (25, 50, 100 or 200 mg) or efavirenz 
      600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 
      300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at week 24, 
      doravirine 100 mg was provided to participants receiving the other doses of 
      doravirine and additional participants were randomized 1:1 to receive once-daily 
      doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). 
      Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml 
      at week 24, and central nervous system (CNS) adverse events (AEs) by weeks 8 and 
      24 (Parts I+II combined). RESULTS: 210 and 132 participants were randomized in 
      Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on 
      efavirenz) were evaluable for Parts I+II combined. At week 24, the proportion of 
      participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 
      73.1% for efavirenz (difference -0.5 [95% CI -12.3, 11.2]). In addition, CNS AEs 
      were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, 
      respectively (difference -20.4 [95% CI -32.6, -7.5]; P=0.002). CONCLUSIONS: 
      Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and 
      superior CNS safety compared with efavirenz 600 mg with TDF/FTC.
FAU - Gatell, Jose M
AU  - Gatell JM
AD  - Hospital Clinic/IDIBAPS, University of Barcelona, Barcelona, Spain.
AD  - Present address: ViiV Healthcare, Barcelona, Spain.
FAU - Morales-Ramirez, Javier O
AU  - Morales-Ramirez JO
AD  - Clinical Research Puerto Rico, San Juan, Puerto Rico.
FAU - Hagins, Debbie P
AU  - Hagins DP
AD  - Chatham County Health Department, Savannah, GA, USA.
FAU - Thompson, Melanie
AU  - Thompson M
AD  - AIDS Research Consortium of Atlanta, Atlanta, GA, USA.
FAU - Arasteh, Keikawus
AU  - Arasteh K
AD  - EPIMED/Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany.
FAU - Hoffmann, Christian
AU  - Hoffmann C
AD  - ICH Study Center, Hamburg, Germany.
FAU - Raffi, Francois
AU  - Raffi F
AD  - Infectious Diseases Department and INSERM CIC 1413, University Hospital of 
      Nantes, Nantes, France.
FAU - Osiyemi, Olayemi
AU  - Osiyemi O
AD  - Triple O Research Institute PA, West Palm Beach, FL, USA.
FAU - Dretler, Robin
AU  - Dretler R
AD  - Infectious Disease Specialists of Atlanta, Decatur, GA, USA.
FAU - Harvey, Charlotte
AU  - Harvey C
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Xu, Xia
AU  - Xu X
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Plettenberg, Andreas
AU  - Plettenberg A
AD  - ifi-Institute for Infections, Hamburg, Germany.
FAU - Smith, Don E
AU  - Smith DE
AD  - Albion Centre, Sydney, Australia.
FAU - Portilla, Joaquin
AU  - Portilla J
AD  - Hospital General Universitario de Alicante/ISABIAL, Alicante, Spain.
FAU - Rugina, Sorin
AU  - Rugina S
AD  - Ovidius University, Clinical Infectious Diseases Hospital, Constanta, Romania.
FAU - Kumar, Sushma
AU  - Kumar S
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Frobose, Colleen
AU  - Frobose C
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Wan, Hong
AU  - Wan H
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Rodgers, Anthony
AU  - Rodgers A
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Hwang, Carey
AU  - Hwang C
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Teppler, Hedy
AU  - Teppler H
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01632345
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 0 (Pyridones)
RN  - 0 (Triazoles)
RN  - 913P6LK81M (doravirine)
RN  - JE6H2O27P8 (efavirenz)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alkynes
MH  - Anti-HIV Agents/*administration & dosage/adverse effects
MH  - Antiretroviral Therapy, Highly Active
MH  - Benzoxazines/*administration & dosage/adverse effects
MH  - Cyclopropanes
MH  - Female
MH  - HIV Infections/*drug therapy/*virology
MH  - HIV-1/*drug effects/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyridones/*administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - Triazoles/*administration & dosage/adverse effects
MH  - Viral Load
MH  - Young Adult
EDAT- 2019/07/30 06:00
MHDA- 2020/07/09 06:00
CRDT- 2019/07/30 06:00
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/07/30 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
PHST- 2019/07/30 06:00 [entrez]
AID - 10.3851/IMP3323 [doi]
PST - ppublish
SO  - Antivir Ther. 2019;24(6):425-435. doi: 10.3851/IMP3323.