Rilpivirine as a potential candidate for the treatment of HIV-associated neurocognitive disorders (HAND)

Ntshangase, Sphamandla; Mdanda, Sipho; Naicker, Tricia; Kruger, Hendrik G.; Govender, Thavendran; Baijnath, Sooraj

doi:10.1007/s10735-019-09826-y

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…In contrast to clinical trials reporting neurocognitive data, our sample was larger [11] or analysed through an extensively wider battery [12] assessing 9 neurocognitive domains. As for trials aviremic patients [11,12], compared to patients on TT, those on DT did not present a higher prevalence of HAND nor reduced performances in specific tasks that may be expected considering recent data on intertwined associations between drug classes/molecules, neurocognitive functions and differential penetration in brain areas [27,28]. This observation has to be interpreted knowing that HAND development timing is not clear and that our neurocognitively tested patients were on DT since a median time of almost 4 years but with a large variability within the sample (minimum 4maximum 124 months).…”

Section: Discussionmentioning

confidence: 68%

“…Thus, despite retrospective, clinical confounders were limited. established CNS reservoir with its dynamics of decay and evolution under cART [7,[13][14][15]27,40], the residual activity of some TT (actually functional dual therapies) may overlap the one of well-patient-tailored DT, but with an addition of toxicity. Lastly, an effective long-lasting and continuous virological suppression in blood, characterising both the groups, may be enough to restore an efficient immune system and this, in turn, may be sufficient for an adequate CNS functioning [12,41].…”

Section: Discussionmentioning

confidence: 99%

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Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV

Trunfio

Rugge

Mighetto

et al. 2020

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Objective: Aim of this study was to compare cerebrospinal fluid (CSF) virological control, biomarkers and neurocognition of neurologically symptomatic patients on dual antiretroviral therapies (DT) versus 2NRTIs-based three-drug regimens (TT). Design:Retrospective monocentric cross-sectional study. Methods:We analysed data from people living with HIV (PLWH) undergoing lumbar puncture for clinical/research reasons with plasma HIV-RNA <200 cp/mL and neurological/neurocognitive symptoms without significant contributing comorbidities.We measured CSF HIV-RNA, inflammation, blood-brain barrier integrity, neuronal damage and astrocytosis biomarkers (5 biomarkers by ELISA and 5 indices by immunoturbidimetry) and recorded the neurocognitive performance (14 tests). CSF escape was defined as any case of CSF HIV-RNA 0.5 Log10 higher than viremia or any case of detectable CSF HIV-RNA coupled with undetectable viremia.Results: 78 patients on TT and 19 on DT were included. Overall, 75.3% male, median age 51 years (46-58), current CD4 count 545 cells/mmc (349-735), time on current regimens 18 months (8-29), but length of plasma suppression 32 months (14-94). The two groups did not differ in terms of HIV-associated neurological diagnoses, demographic and viro-immunological features. Undetectable CSF HIV-RNA (73.7% in DT vs 78.2% in TT, p.67) and CSF escape (21.1% in DT vs. 19.2% in TT, p.86) did not differ. No difference was observed in depression, anxiety, neurocognition (in 63 participants) nor in any tested biomarker. Conclusions:In PLWH with neurological/neurocognitive symptoms, peripherally effective DT can show CSF viro-suppression, inflammation, neuronal and astrocyte integrity and neurocognition comparable to TT.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV

Trunfio

Rugge

Mighetto

et al. 2020

Aids

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“…After 0.5 h, NVP was strongly expressed only in the cortical pathways and corpus callosum. MALDI-MSI showed that rilpivirine (RPV) was highly enriched in corpus callosum and hippocampal structures and after 2 h MALDI-MSI was unable to detect the drug, as detected by LC-MS/MS [ 74 ] ( Figure 3 A). Both anti-CNS HIV drugs were concentrated in brain regions associated with the development of neurodegenerative lesions, suggesting a longer drug residence time in brain regions to provide a higher degree of CNS efficacy.…”

Section: Mass Spectrometry Imaging For Assessing Intracerebral Pharma...mentioning

confidence: 99%

“…A high degree of m / z 367.0 localization was observed in hippocampal structures (HPF) and corpus callosum (CC) at 0.25 h. Reprinted with permission from Ref. [ 74 ]. © 2019, Sphamandla Ntshangase.…”

Section: Mass Spectrometry Imaging For Assessing Intracerebral Pharma...mentioning

confidence: 99%

Imaging Technologies for Cerebral Pharmacokinetic Studies: Progress and Perspectives

2022

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Pharmacokinetic assessment of drug disposition processes in vivo is critical in predicting pharmacodynamics and toxicology to reduce the risk of inappropriate drug development. The blood–brain barrier (BBB), a special physiological structure in brain tissue, hinders the entry of targeted drugs into the central nervous system (CNS), making the drug concentrations in target tissue correlate poorly with the blood drug concentrations. Additionally, once non-CNS drugs act directly on the fragile and important brain tissue, they may produce extra-therapeutic effects that may impair CNS function. Thus, an intracerebral pharmacokinetic study was developed to reflect the disposition and course of action of drugs following intracerebral absorption. Through an increasing understanding of the fine structure in the brain and the rapid development of analytical techniques, cerebral pharmacokinetic techniques have developed into non-invasive imaging techniques. Through non-invasive imaging techniques, molecules can be tracked and visualized in the entire BBB, visualizing how they enter the BBB, allowing quantitative tools to be combined with the imaging system to derive reliable pharmacokinetic profiles. The advent of imaging-based pharmacokinetic techniques in the brain has made the field of intracerebral pharmacokinetics more complete and reliable, paving the way for elucidating the dynamics of drug action in the brain and predicting its course. The paper reviews the development and application of imaging technologies for cerebral pharmacokinetic study, represented by optical imaging, radiographic autoradiography, radionuclide imaging and mass spectrometry imaging, and objectively evaluates the advantages and limitations of these methods for predicting the pharmacodynamic and toxic effects of drugs in brain tissues.

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Screening Accuracy of Mini Addenbrooke’s Cognitive Examination Test for HIV-Associated Neurocognitive Disorders in People Ageing with HIV

et al. 2022

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Rilpivirine as a potential candidate for the treatment of HIV-associated neurocognitive disorders (HAND)

Cited by 9 publications

References 30 publications

Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV

Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV

Imaging Technologies for Cerebral Pharmacokinetic Studies: Progress and Perspectives

Screening Accuracy of Mini Addenbrooke’s Cognitive Examination Test for HIV-Associated Neurocognitive Disorders in People Ageing with HIV

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