PMID- 31121013
OWN - NLM
STAT- MEDLINE
DCOM- 20210106
LR  - 20210106
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 70
IP  - 7
DP  - 2020 Mar 17
TI  - Once-daily Doravirine for Initial Treatment of Adults Living With Human 
      Immunodeficiency Virus-1: An Integrated Safety Analysis.
PG  - 1336-1343
LID - 10.1093/cid/ciz423 [doi]
AB  - BACKGROUND: A prespecified integrated safety analysis was conducted for 3 
      doravirine (DOR) double-blind trials (Phase IIb: P007 [NCT01632345]; Phase III: 
      DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]). METHODS: DOR (100 mg) 
      arms from these trials were compared with darunavir plus ritonavir (DRV+r) in 
      DRIVE-FORWARD and efavirenz (EFV) in P007 and DRIVE-AHEAD. Background therapies 
      were emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in P007; 
      abacavir/lamivudine (ABC/3TC) or FTC/TDF in DRIVE-FORWARD; and 3TC/TDF for DOR 
      and FTC/TDF for EFV in DRIVE-AHEAD. The primary endpoint was the proportion of 
      participants discontinuing due to adverse events (AEs) through Week 48. RESULTS: 
      Discontinuation rates due to AEs were similar for participants on DOR and DRV+r 
      (2.5% vs 3.1%, respectively) and lower for those on DOR than for those on EFV 
      (2.5% vs 6.6%, respectively). Rates of drug-related AEs for DOR, DRV+r, and EFV 
      were 30.9%, 32.1%, and 61.4%, respectively. In an analysis of DOR versus EFV, the 
      treatment difference for discontinuations due to AEs was -3.4%, favoring DOR (95% 
      confidence interval -6.2 to -0.8; P = .012). Fewer participants experienced 
      neuropsychiatric AEs on DOR than on EFV (25.0% vs 55.9%, respectively), and fewer 
      experienced diarrhea on DOR than on DRV+r (12.4% vs 22.5%, respectively). Changes 
      from baseline in most lipid parameters also favored DOR. CONCLUSIONS: At Week 48, 
      DOR at 100 mg had a favorable safety profile compared with EFV or DRV+r and a 
      favorable tolerability profile compared with EFV. CLINICAL TRIALS REGISTRATION: 
      NCT01632345; NCT02275780 and NCT02403674.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Thompson, Melanie
AU  - Thompson M
AD  - AIDS Research Consortium, Atlanta, Georgia.
FAU - Orkin, Chloe
AU  - Orkin C
AD  - Queen Mary University, London, United Kingdom.
FAU - Molina, Jean-Michel
AU  - Molina JM
AD  - University of Paris Diderot, Hopital Saint-Louis, France.
FAU - Sax, Paul
AU  - Sax P
AD  - Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
FAU - Cahn, Pedro
AU  - Cahn P
AD  - Fundacion Huesped, Buenos Aires, Argentina.
FAU - Squires, Kathleen
AU  - Squires K
AD  - Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, 
      Pennsylvania.
FAU - Xu, Xia
AU  - Xu X
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
FAU - Rodgers, Anthony
AU  - Rodgers A
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
FAU - Kumar, Sushma
AU  - Kumar S
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
FAU - Teppler, Hedy
AU  - Teppler H
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
FAU - Martin, Elizabeth
AU  - Martin E
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
FAU - Hanna, George
AU  - Hanna G
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
FAU - Hwang, Carey
AU  - Hwang C
AD  - Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey.
LA  - eng
SI  - ClinicalTrials.gov/NCT01632345
SI  - ClinicalTrials.gov/NCT02275780
SI  - ClinicalTrials.gov/NCT02403674
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Pyridones)
RN  - 0 (Triazoles)
RN  - 913P6LK81M (doravirine)
RN  - 99YXE507IL (Tenofovir)
RN  - G70B4ETF4S (Emtricitabine)
SB  - IM
MH  - Adult
MH  - *Anti-HIV Agents/adverse effects
MH  - Emtricitabine/therapeutic use
MH  - *HIV Infections/drug therapy
MH  - *HIV-1
MH  - Humans
MH  - Pyridones
MH  - Tenofovir/therapeutic use
MH  - Triazoles
OTO - NOTNLM
OT  - HIV safety
OT  - darunavir/ritonavir
OT  - doravirine
OT  - efavirenz
OT  - nonnucleoside reverse transcriptase inhibitor safety
EDAT- 2019/05/24 06:00
MHDA- 2021/01/07 06:00
CRDT- 2019/05/24 06:00
PHST- 2019/01/31 00:00 [received]
PHST- 2019/05/22 00:00 [accepted]
PHST- 2019/05/24 06:00 [pubmed]
PHST- 2021/01/07 06:00 [medline]
PHST- 2019/05/24 06:00 [entrez]
AID - 5497865 [pii]
AID - 10.1093/cid/ciz423 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2020 Mar 17;70(7):1336-1343. doi: 10.1093/cid/ciz423.