Imperial College London

ProfessorRobinShattock

Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mora-Peris:2015:jac/dkv326,
author = {Mora-Peris, B and Winston, A and Garvey, L and Else, LJ and Shattock, RJ and Herrera, C},
doi = {jac/dkv326},
journal = {Journal of Antimicrobial Chemotherapy},
pages = {235--243},
title = {HIV-1 CNS in vitro infectivity models based on clinical CSF samples},
url = {http://dx.doi.org/10.1093/jac/dkv326},
volume = {71},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background The concentration of antiretrovirals in CSF is often utilized as a surrogate for CNS drug exposure. This measurement does not consider pharmacodynamic or combinative effects of ART. We have developed a novel endpoint measurement to assess antiretroviral activity of CSF from subjects on ART.Methods CSF samples were obtained from patients receiving tenofovir/emtricitabine (245/200 mg once daily) with either rilpivirine (25 mg once daily) or lopinavir/ritonavir/maraviroc (400/100/150 mg twice daily) and HIV-uninfected controls. Antiviral activity of ART-containing CSF was assessed in cell cultures using PBMCs and neuro-derived glial (U87) and astrocyte (373) cell lines. Infectivity model half-maximal inhibitory concentration (IMIC50) values were calculated and expressed as −log2IMIC50. Results were correlated with CSF antiretroviral concentrations.Results Compared with controls, CSF from both ART studies demonstrated in vitro antiretroviral activity in all models. CSF antiretroviral activity of patients on lopinavir/ritonavir/maraviroc was significantly greater than that of patients on rilpivirine [−log2IMIC50 (95% CI) 4.82 (4.74–4.89) versus 3.43 (3.33–3.54) in PBMCs, 3.06 (2.98–3.15) versus 2.56 (2.46–2.65) in U87 cells and 6.00 (6.11–5.88) versus 4.90 (5.09–4.72) in 373 cells, respectively]. Positive correlations were observed for individual CSF antiretroviral activity in different cellular models with CSF concentrations of rilpivirine (P=0.040 in 373 cells) and lopinavir (P=0.048 in 373 cells), but not maraviroc.Conclusions Antiviral activity of CSF from patients on ART was successfully calculated and was greater with a regimen containing four active drugs compared with three active drugs. The use of neuro-derived cell lines alongside PBMCs to assess the effect of ART on CSF may act as a useful future clinical research tool.
AU - Mora-Peris,B
AU - Winston,A
AU - Garvey,L
AU - Else,LJ
AU - Shattock,RJ
AU - Herrera,C
DO - jac/dkv326
EP - 243
PY - 2015///
SN - 1460-2091
SP - 235
TI - HIV-1 CNS in vitro infectivity models based on clinical CSF samples
T2 - Journal of Antimicrobial Chemotherapy
UR - http://dx.doi.org/10.1093/jac/dkv326
VL - 71
ER -