PMID- 27624569
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20171214
IS  - 1460-2091 (Electronic)
IS  - 0305-7453 (Linking)
VI  - 72
IP  - 1
DP  - 2017 Jan
TI  - Integrase strand-transfer inhibitor polymorphic and accessory resistance 
      substitutions in patients with acute/recent HIV infection.
PG  - 205-209
AB  - OBJECTIVES: The most recent guidelines suggest using integrase strand-transfer 
      inhibitors (InSTIs) as the preferred antiretroviral regimens for naive 
      HIV-infected individuals. However, resistance to InSTIs is not monitored in many 
      centres at baseline. This study aimed to evaluate the prevalence of InSTI 
      resistance substitutions in newly diagnosed patients with acute/recent HIV 
      infection. METHODS: Genotypic drug resistance tests were performed in all 
      consecutive patients prospectively enrolled with a documented infection of <6 
      months, from 12 May 2015 to 12 May 2016. Sequences were obtained by 
      high-throughput sequencing. RESULTS: Five out of 36 consecutive patients (13.89%, 
      95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains 
      carrying InSTI polymorphisms or substitutions conferring low-level resistance to 
      raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one 
      patient had the Q95K substitution. All cases were MSM patients infected with 
      subtype B strains. Viral loads ranged from 2.92 to 6.95 log(10) copies/mL. In all 
      cases, the mutational viral load was high. Three patients initiated 
      dolutegravir-based regimens and became undetectable at first viral load control. 
      There were no major viral or epidemiological differences when compared with 
      patients without InSTI substitutions. CONCLUSIONS: Although signature InSTI 
      substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, 
      polymorphisms and substitutions conferring low-level resistance to raltegravir 
      and elvitegravir were frequently found in a baseline genotypic test. All cases 
      were infected with subtype B, the most frequent in Europe. In the context of 
      primary HIV infection, virological response should be carefully monitored to 
      evaluate the impact of these InSTI polymorphisms and substitutions.
CI  - (c) The Author 2016. Published by Oxford University Press on behalf of the British 
      Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, 
      please e-mail: journals.permissions@oup.com.
FAU - Ambrosioni, J
AU  - Ambrosioni J
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain jambrosioni@intramed.net.
FAU - Nicolas, D
AU  - Nicolas D
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
FAU - Manzardo, C
AU  - Manzardo C
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
FAU - Aguero, F
AU  - Aguero F
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
FAU - Blanco, J L
AU  - Blanco JL
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
FAU - Mosquera, M M
AU  - Mosquera MM
AD  - Laboratory of Virology, Microbiology Service, Hospital Clinic-ISGLOBAL, 
      University of Barcelona, Barcelona, Spain.
FAU - Penafiel, J
AU  - Penafiel J
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
FAU - Gatell, J M
AU  - Gatell JM
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
FAU - Marcos, M A
AU  - Marcos MA
AD  - Laboratory of Virology, Microbiology Service, Hospital Clinic-ISGLOBAL, 
      University of Barcelona, Barcelona, Spain.
FAU - Miro, J M
AU  - Miro JM
AD  - Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 
      Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160913
PL  - England
TA  - J Antimicrob Chemother
JT  - The Journal of antimicrobial chemotherapy
JID - 7513617
RN  - 0 (HIV Integrase Inhibitors)
RN  - EC 2.7.7.- (HIV Integrase)
SB  - IM
CIN - J Antimicrob Chemother. 2017 May 1;72 (5):1546-1547. PMID: 28158344
CIN - J Antimicrob Chemother. 2017 May 1;72 (5):1547-1548. PMID: 28333247
MH  - Adult
MH  - Amino Acid Substitution
MH  - *Drug Resistance, Viral
MH  - Europe
MH  - Female
MH  - Genotyping Techniques
MH  - HIV Infections/*drug therapy/*virology
MH  - HIV Integrase/*genetics
MH  - HIV Integrase Inhibitors/*pharmacology
MH  - Humans
MH  - Male
MH  - Mutation Rate
MH  - *Mutation, Missense
MH  - Prospective Studies
MH  - Sequence Analysis, DNA
EDAT- 2016/09/15 06:00
MHDA- 2017/08/15 06:00
CRDT- 2016/09/15 06:00
PHST- 2016/06/17 00:00 [received]
PHST- 2016/08/01 00:00 [revised]
PHST- 2016/08/10 00:00 [accepted]
PHST- 2016/09/15 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/15 06:00 [entrez]
AID - dkw376 [pii]
AID - 10.1093/jac/dkw376 [doi]
PST - ppublish
SO  - J Antimicrob Chemother. 2017 Jan;72(1):205-209. doi: 10.1093/jac/dkw376. Epub 
      2016 Sep 13.