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Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain

Overview of attention for article published in Retrovirology, October 2017
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Title
Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain
Published in
Retrovirology, October 2017
DOI 10.1186/s12977-017-0370-5
Pubmed ID
Authors

Eugene L. Asahchop, Oussama Meziane, Manmeet K. Mamik, Wing F. Chan, William G. Branton, Lothar Resch, M. John Gill, Elie Haddad, Jean V. Guimond, Mark A. Wainberg, Glen B. Baker, Eric A. Cohen, Christopher Power

Abstract

In patients with HIV/AIDS receiving antiretroviral therapy (ART), HIV-1 persistence in brain tissue is a vital and unanswered question. HIV-1 infects and replicates in resident microglia and trafficking macrophages within the brain although the impact of individual ART drugs on viral infection within these brain myeloid cells is unknown. Herein, the effects of contemporary ART drugs were investigated using in vitro and in vivo models of HIV-1 brain infection. The EC50 values for specific ART drugs in HIV-infected human microglia were significantly higher compared to bone marrow-derived macrophages and peripheral blood mononuclear cells. Intracellular ART drug concentrations in microglia were significantly lower than in human lymphocytes. In vivo brain concentrations of ART drugs in mice were 10 to 100-fold less in brain tissues compared with plasma and liver levels. In brain tissues from untreated HIV-infected BLT mice, HIV-encoded RNA, DNA and p24 were present in human leukocytes while ART eradicated viral RNA and DNA in both brain and plasma. Interruption of ART resulted in detectable viral RNA and DNA and increased human CD68 expression in brains of HIV-infected BLT mice. In aviremic HIV/AIDS patients receiving effective ART, brain tissues that were collected within hours of last ART dosing showed HIV-encoded RNA and DNA with associated neuroinflammatory responses. ART drugs show variable concentrations and efficacies in brain myeloid cells and tissues in drug-specific manner. Despite low drug concentrations in brain, experimental ART suppressed HIV-1 infection in brain although HIV/AIDS patients receiving effective ART had detectable HIV-1 in brain. These findings suggest that viral suppression in brain is feasible but new approaches to enhancing ART efficacy and concentrations in brain are required for sustained HIV-1 eradication from brain.

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The data shown below were collected from the profiles of 3 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 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 19%
Student > Bachelor 6 10%
Researcher 5 8%
Student > Master 5 8%
Student > Doctoral Student 4 6%
Other 9 15%
Unknown 21 34%
Readers by discipline Count As %
Medicine and Dentistry 13 21%
Immunology and Microbiology 7 11%
Agricultural and Biological Sciences 6 10%
Neuroscience 5 8%
Biochemistry, Genetics and Molecular Biology 4 6%
Other 4 6%
Unknown 23 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 31 October 2017.
All research outputs
#14,574,276
of 23,344,526 outputs
Outputs from Retrovirology
#702
of 1,115 outputs
Outputs of similar age
#181,871
of 326,732 outputs
Outputs of similar age from Retrovirology
#9
of 12 outputs
Altmetric has tracked 23,344,526 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,115 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one is in the 33rd percentile – i.e., 33% of its peers scored the same or lower than it.
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 326,732 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.