PMID- 28453836
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20220410
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 215
IP  - 6
DP  - 2017 Mar 15
TI  - Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and 
      Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens 
      Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide.
PG  - 920-927
LID - 10.1093/infdis/jix015 [doi]
AB  - BACKGROUND: The presence of transmitted drug resistance mutations (TDRMs) in 
      antiretroviral treatment (ART)-naive patients can adversely affect the outcome of 
      ART. METHODS: Resistance testing was conducted in 6704 ART-naive subjects 
      predominantly from the United States and Europe in 9 clinical studies conducted 
      by Gilead Sciences from 2000 to 2013. RESULTS: The presence of TDRMs increased 
      during this period (from 5.2% to 11.4%), primarily driven by an increase in 
      nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations 
      (from 0.3% to 7.1%), particularly K103N/S (increase from 0.3% to 5.3%). 
      Nucleoside/nucleotide RT inhibitor mutations were found in 3.1% of patients. Only 
      1 patient had K65R (0.01%) and 7 had M184V/I (0.1%), despite high use of 
      tenofovir disoproxil fumarate (TDF), emtricitabine, and lamivudine and potential 
      transmission of resistance to these drugs. At least 1 thymidine-analogue 
      mutations was present in 2.7% of patients with 0.07% harboring T215Y/F and 2.7% 
      harboring T215 revertant mutations (T215rev). Patients with the combination of 
      M41L + L210W + T215rev showed full human immunodeficiency virus RNA suppression 
      while receiving a TDF- or tenofovir alafenamide-containing regimen. CONCLUSIONS: 
      There was an overall increase of TDRMs among patients enrolling in clinical 
      trials from 2000 through 2013, driven primarily by an increase in NNRTI 
      resistance. However, the presence of common TDRMs, including thymidine-analogue 
      mutations/T215rev, showed no impact on response to TDF- or tenofovir 
      alafenamide-containing regimens.
CI  - (c) The Author 2017. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail 
      journals.permissions@oup.com.
FAU - Margot, Nicolas A
AU  - Margot NA
AD  - Gilead Sciences, Foster City, California, USA.
FAU - Wong, Pamela
AU  - Wong P
AD  - Gilead Sciences, Foster City, California, USA.
FAU - Kulkarni, Rima
AU  - Kulkarni R
AD  - Gilead Sciences, Foster City, California, USA.
FAU - White, Kirsten
AU  - White K
AD  - Gilead Sciences, Foster City, California, USA.
FAU - Porter, Danielle
AU  - Porter D
AD  - Gilead Sciences, Foster City, California, USA.
FAU - Abram, Michael E
AU  - Abram ME
AD  - Gilead Sciences, Foster City, California, USA.
FAU - Callebaut, Christian
AU  - Callebaut C
AD  - Gilead Sciences, Foster City, California, USA.
FAU - Miller, Michael D
AU  - Miller MD
AD  - Gilead Sciences, Foster City, California, USA.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 2T8Q726O95 (Lamivudine)
RN  - 99YXE507IL (Tenofovir)
RN  - EL9943AG5J (tenofovir alafenamide)
RN  - G70B4ETF4S (Emtricitabine)
RN  - JAC85A2161 (Adenine)
RN  - OF5P57N2ZX (Alanine)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Adenine/*analogs & derivatives/therapeutic use
MH  - Adult
MH  - Alanine
MH  - Anti-HIV Agents/*therapeutic use
MH  - Drug Resistance, Viral/*genetics
MH  - Emtricitabine/therapeutic use
MH  - Europe
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - HIV-1/drug effects/*genetics
MH  - Humans
MH  - Lamivudine/therapeutic use
MH  - Male
MH  - Mutation, Missense
MH  - Reverse Transcriptase Inhibitors/therapeutic use
MH  - Tenofovir/*therapeutic use
MH  - Thymidine/analogs & derivatives
MH  - United States
OTO - NOTNLM
OT  - HIV-1.
OT  - tenofovir alafenamide
OT  - tenofovir disoproxil fumarate
OT  - transmitted resistance
EDAT- 2017/04/30 06:00
MHDA- 2017/07/01 06:00
CRDT- 2017/04/29 06:00
PHST- 2016/10/14 00:00 [received]
PHST- 2017/01/05 00:00 [accepted]
PHST- 2017/04/29 06:00 [entrez]
PHST- 2017/04/30 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
AID - 2964643 [pii]
AID - 10.1093/infdis/jix015 [doi]
PST - ppublish
SO  - J Infect Dis. 2017 Mar 15;215(6):920-927. doi: 10.1093/infdis/jix015.