↓ Skip to main content

The NRTIs Lamivudine, Stavudine and Zidovudine Have Reduced HIV-1 Inhibitory Activity in Astrocytes

Overview of attention for article published in PLOS ONE, April 2013
Altmetric Badge

Mentioned by

twitter
1 X user

Citations

dimensions_citation
45 Dimensions

Readers on

mendeley
46 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
The NRTIs Lamivudine, Stavudine and Zidovudine Have Reduced HIV-1 Inhibitory Activity in Astrocytes
Published in
PLOS ONE, April 2013
DOI 10.1371/journal.pone.0062196
Pubmed ID
Authors

Lachlan R. Gray, Gilda Tachedjian, Anne M. Ellett, Michael J. Roche, Wan-Jung Cheng, Gilles J. Guillemin, Bruce J. Brew, Stuart G. Turville, Steve L. Wesselingh, Paul R. Gorry, Melissa J. Churchill

Abstract

HIV-1 establishes infection in astrocytes and macroage-lineage cells of the central nervous system (CNS). Certain antiretroviral drugs (ARVs) can penetrate the CNS, and are therefore often used in neurologically active combined antiretroviral therapy (Neuro-cART) regimens, but their relative activity in the different susceptible CNS cell populations is unknown. Here, we determined the HIV-1 inhibitory activity of CNS-penetrating ARVs in astrocytes and macrophage-lineage cells. Primary human fetal astrocytes (PFA) and the SVG human astrocyte cell line were used as in vitro models for astrocyte infection, and monocyte-derived macrophages (MDM) were used as an in vitro model for infection of macrophage-lineage cells. The CNS-penetrating ARVs tested were the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir (ABC), lamivudine (3TC), stavudine (d4T) and zidovudine (ZDV), the non-NRTIs efavirenz (EFV), etravirine (ETR) and nevirapine (NVP), and the integrase inhibitor raltegravir (RAL). Drug inhibition assays were performed using single-round HIV-1 entry assays with luciferase viruses pseudotyped with HIV-1 YU-2 envelope or vesicular stomatitis virus G protein (VSV-G). All the ARVs tested could effectively inhibit HIV-1 infection in macrophages, with EC90s below concentrations known to be achievable in the cerebral spinal fluid (CSF). Most of the ARVs had similar potency in astrocytes, however the NRTIs 3TC, d4T and ZDV had insufficient HIV-1 inhibitory activity in astrocytes, with EC90s 12-, 187- and 110-fold greater than achievable CSF concentrations, respectively. Our data suggest that 3TC, d4T and ZDV may not adequately target astrocyte infection in vivo, which has potential implications for their inclusion in Neuro-cART regimens.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user 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 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
Unknown 45 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 22%
Student > Master 6 13%
Student > Doctoral Student 5 11%
Student > Postgraduate 4 9%
Student > Bachelor 3 7%
Other 9 20%
Unknown 9 20%
Readers by discipline Count As %
Medicine and Dentistry 12 26%
Agricultural and Biological Sciences 7 15%
Immunology and Microbiology 4 9%
Chemistry 4 9%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 6 13%
Unknown 11 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 05 May 2013.
All research outputs
#20,741,146
of 23,342,664 outputs
Outputs from PLOS ONE
#178,730
of 199,619 outputs
Outputs of similar age
#153,937
of 176,510 outputs
Outputs of similar age from PLOS ONE
#4,343
of 5,150 outputs
Altmetric has tracked 23,342,664 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 199,619 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.3. This one is in the 1st percentile – i.e., 1% 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 176,510 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5,150 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.