ArticleThe Journal of antimicrobial chemotherapy2016
HIV-1 CNS in vitro infectivity models based on clinical CSF samples.
Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 7 citations in OpenAlex.
- CNS-Targeted Antiretroviral Strategies: When Are They Needed and What to Choose.Current HIV/AIDS reports · 2018Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
methodsCSF 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.
resultsCompared 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.
conclusionsAntiviral 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.
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