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Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses

Overview of attention for article published in Retrovirology, April 2016
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  • Above-average Attention Score compared to outputs of the same age (55th percentile)
  • Good Attention Score compared to outputs of the same age and source (65th percentile)

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6 X users

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42 Mendeley
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Title
Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses
Published in
Retrovirology, April 2016
DOI 10.1186/s12977-016-0265-x
Pubmed ID
Authors

Hanh T. Pham, Thibault Mesplède, Mark A. Wainberg

Abstract

Recommended regimens for HIV-positive individuals include the co-administration of dolutegravir (DTG) with two reverse transcriptase inhibitors (RTIs). Although rare, emerging resistance against DTG is often associated with the R263K substitution in integrase. In-vitro-selected R263K was associated with impaired viral replication capacity, DNA integration, and integrase strand-transfer activity, especially when accompanied by the secondary mutation H51Y. Given the reduced fitness of RTI-resistant viruses, we investigated potential impacts on viral replication of combining R263K and H51Y/R263K with major RTI-resistance substitutions including K65R, L74V, K103N, E138K, and M184I/V. We combined the R263K or H51Y/R263K with RTI-resistance mutations into the proviral plasmid pNL4.3 and measured the resulting viral infectiousness, replication capacity, and ability to integrate viral DNA into host cells. Infectiousness was determined by luciferase assay in TZM-bl cells. Replicative capacity was monitored over 7 days and viral DNA integration was studied by real-time Alu-qPCR in PM1 cells. We found that viral infectiousness, replication capacities and integration levels were greatly reduced in triple mutants, i.e. H51Y/R263K plus a RT mutation, and moderately reduced in double mutants, i.e. R263K plus a RT mutation, compared to wild-type and single RT-mutant viruses. Our findings help to explain the absence of RTI mutations in individuals who experienced DTG-treatment failure.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 2%
Unknown 41 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 17%
Student > Master 7 17%
Researcher 6 14%
Other 5 12%
Professor 3 7%
Other 7 17%
Unknown 7 17%
Readers by discipline Count As %
Medicine and Dentistry 15 36%
Immunology and Microbiology 5 12%
Agricultural and Biological Sciences 4 10%
Biochemistry, Genetics and Molecular Biology 3 7%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Other 3 7%
Unknown 10 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 May 2017.
All research outputs
#12,660,264
of 22,867,327 outputs
Outputs from Retrovirology
#541
of 1,107 outputs
Outputs of similar age
#132,495
of 298,447 outputs
Outputs of similar age from Retrovirology
#8
of 23 outputs
Altmetric has tracked 22,867,327 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,107 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 50% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 298,447 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.