@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}
}

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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  - 

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