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Article ; Online: Editorial commentary: cerebrospinal fluid inhibitory quotients of antiretroviral drugs.

Fletcher, Courtney V

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2015 Volume 60, Issue 2, Page(s) 318–320

MeSH term(s)	AIDS Dementia Complex/drug therapy ; AIDS Dementia Complex/prevention & control ; Anti-Retroviral Agents/pharmacokinetics ; Cerebrospinal Fluid/chemistry ; Female ; HIV/isolation & purification ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Male
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2015-01-15
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciu775
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 480: Show issues

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Article ; Online: Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19.

Zhou, Xiao-Jian / Horga, Arantxa / Puri, Adeep / Winchester, Lee / Montrond, Maureen / Pietropaolo, Keith / Belanger, Bruce / Fletcher, Courtney V / Hammond, Janet

The Journal of antimicrobial chemotherapy

2024

Abstract: Background: Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug ... ...

Abstract	Background: Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved. Objectives: This Phase 1 study in healthy subjects aimed to assess the bronchopulmonary pharmacokinetics, safety and tolerability of repeated doses of bemnifosbuvir. Methods: A total of 24 subjects were assigned to receive bemnifosbuvir twice daily at doses of 275, 550 or 825 mg for up to 3.5 days. Results: AT-511, the free base of bemnifosbuvir, was largely eliminated from the plasma within 6 h post dose in all dosing groups. Antiviral drug levels of bemnifosbuvir were consistently achieved in the lungs with bemnifosbuvir 550 mg twice daily. The mean level of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, measured in the epithelial lining fluid of the lungs was 0.62 µM at 4-5 h post dose. This exceeded the target in vitro 90% effective concentration (EC90) of 0.5 µM for antiviral drug exposure against SARS-CoV-2 replication in human airway epithelial cells. Bemnifosbuvir was well tolerated across all doses tested, and most treatment-emergent adverse events reported were mild in severity and resolved. Conclusions: The favourable pharmacokinetics and safety profile of bemnifosbuvir demonstrates its potential as an oral antiviral treatment for COVID-19, with 550 mg bemnifosbuvir twice daily currently under further clinical evaluation in persons with COVID-19.
Language	English
Publishing date	2024-05-06
Publishing country	England
Document type	Journal Article
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkae122
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The Contributions of Clinical Pharmacology to HIV Cure Research.

Fletcher, Courtney V / Dyavar, Shetty Ravi / Acharya, Arpan / Byrareddy, Siddappa N

Clinical pharmacology and therapeutics

2021 Volume 110, Issue 2, Page(s) 334–345

Abstract: Combination antiretroviral therapy (ART) can suppress plasma HIV-RNA to < 50 copies/mL, decrease HIV transmission, reduce mortality, and improve quality of life for people living with HIV. ART cannot, however, eliminate HIV from an infected individual. ... ...

Abstract	Combination antiretroviral therapy (ART) can suppress plasma HIV-RNA to < 50 copies/mL, decrease HIV transmission, reduce mortality, and improve quality of life for people living with HIV. ART cannot, however, eliminate HIV from an infected individual. The primary barrier to cure HIV infection is the multiple reservoir sites, including adipose tissue, bone marrow, central nervous system, liver, lungs, male and female reproductive system, secondary lymph nodes, and gut-associated lymphoid tissue, established 1 to 2 weeks after acquisition of HIV. Additional challenges include understanding the mechanism(s) by which HIV is maintained at low or undetectable levels and developing treatments that will eradicate or produce a sustained suppression of virus without ART. To date, the most extensive clinical investigations of cure strategies have been the shock-and-kill approach using histone deacetylase inhibitors (HDACis) to induce reactivation of latent HIV. Despite evidence for HIV latency reversal, HDACis alone have not decreased the size of the latent reservoir. Clinical pharmacologic explanations for these results include a low inhibitory quotient (i.e., low potency) within the reservoir sites and intrinsic (e.g., sex differences and reservoir size) and extrinsic (physiochemical and pharmacokinetic drug characteristics) factors. We offer an outline of desired clinical pharmacologic attributes for therapeutics intended for clinical HIV cure research and call for research teams to have early and ongoing involvement of clinical pharmacologists. We believe such a collective effort will provide a solid scientific basis and hope for reaching the goal of a cure for HIV infection.
MeSH term(s)	Animals ; Anti-Retroviral Agents/pharmacokinetics ; Anti-Retroviral Agents/therapeutic use ; Biomarkers ; CD4-Positive T-Lymphocytes ; DNA, Viral/metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; HIV Infections/drug therapy ; HIV Infections/physiopathology ; Half-Life ; Histone Deacetylase Inhibitors/pharmacokinetics ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Metabolic Clearance Rate ; Pharmacology, Clinical ; Quality of Life ; Sex Factors ; Tissue Distribution/physiology ; Viral Load/drug effects ; Virus Latency/drug effects
Chemical Substances	Anti-Retroviral Agents ; Biomarkers ; DNA, Viral ; Histone Deacetylase Inhibitors
Language	English
Publishing date	2021-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2237
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Article ; Online: ACE-2, TMPRSS2, and Neuropilin-1 Receptor Expression on Human Brain Astrocytes and Pericytes and SARS-CoV-2 Infection Kinetics.

Malik, Johid Reza / Acharya, Arpan / Avedissian, Sean N / Byrareddy, Siddappa N / Fletcher, Courtney V / Podany, Anthony T / Dyavar, Shetty Ravi

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Angiotensin Converting Enzyme 2 (ACE-2), Transmembrane Serine Protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells and are characterized at the molecular level. Some evidence on the ...

Abstract	Angiotensin Converting Enzyme 2 (ACE-2), Transmembrane Serine Protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells and are characterized at the molecular level. Some evidence on the expression of entry receptors at mRNA and protein levels in brain cells is available, but co-expression of these receptors and confirmatory evidence on brain cells is lacking. SARS-CoV-2 infects some brain cell types, but infection susceptibility, multiple entry receptor density, and infection kinetics are rarely reported in specific brain cell types. Highly sensitive Taqman ddPCR, flow-cytometry and immunocytochemistry assays were used to quantitate the expression of ACE-2, TMPRSS-2 and Neuropilin-1 at mRNA and protein levels on human brain-extracted pericytes and astrocytes, which are an integral part of the Blood-Brain-Barrier (BBB). Astrocytes showed moderate ACE-2 (15.9 ± 1.3%, Mean ± SD, n = 2) and TMPRSS-2 (17.6%) positive cells, and in contrast show high Neuropilin-1 (56.4 ± 39.8%, n = 4) protein expression. Whereas pericytes showed variable ACE-2 (23.1 ± 20.7%, n = 2), Neuropilin-1 (30.3 ± 7.5%, n = 4) protein expression and higher TMPRSS-2 mRNA (667.2 ± 232.3, n = 3) expression. Co-expression of multiple entry receptors on astrocytes and pericytes allows entry of SARS-CoV-2 and progression of infection. Astrocytes showed roughly four-fold more virus in culture supernatants than pericytes. SARS-CoV-2 cellular entry receptor expression and "in vitro" viral kinetics in astrocytes and pericytes may improve our understanding of viral infection "in vivo". In addition, this study may facilitate the development of novel strategies to counter the effects of SARS-CoV-2 and inhibit viral infection in brain tissues to prevent the spread and interference in neuronal functions.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Neuropilin-1/genetics ; Angiotensin-Converting Enzyme 2/genetics ; Astrocytes ; Pericytes ; Kinetics ; Blood-Brain Barrier ; Serine Endopeptidases/genetics
Chemical Substances	Neuropilin-1 (144713-63-3) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; TMPRSS2 protein, human (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2023-05-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24108622
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Article ; Online: Quantification of nine antiretroviral drugs in cerebrospinal fluid: An approach to overcome sample collection tube adsorption.

Mykris, Timothy M / Weinhold, Jonathan / Winchester, Lee C / Scarsi, Kimberly K / Fletcher, Courtney V / Podany, Anthony T / Avedissian, Sean N

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2023 Volume 1227, Page(s) 123810

Abstract: A highly sensitive LC-MS/MS methods were developed and validated to quantify nine antiretrovirals (atazanavir [ATV], tenofovir [TFV], emtricitabine [FTC], darunavir [DRV], dolutegravir [DTG], efavirenz [EFV], lamivudine [3TC], raltegravir [RAL], and ... ...

Abstract	A highly sensitive LC-MS/MS methods were developed and validated to quantify nine antiretrovirals (atazanavir [ATV], tenofovir [TFV], emtricitabine [FTC], darunavir [DRV], dolutegravir [DTG], efavirenz [EFV], lamivudine [3TC], raltegravir [RAL], and ritonavir [RTV]) in human cerebral spinal fluid (CSF). The approach remedies adsorption issues caused by polypropylene based sample collection tubes. 1% ammonium hydroxide in methanol was added in an amount equal to the volume of each quality control (QC) or patient sample. Protein precipitation was utilized with a CSF sample volume of 100 μL and a 100 μL of methanol:ACN and vortexed. Chromatographic separation was achieved with a 3 × 100 ACE® C18 column for ATV, DRV, DTG, EFV, RTV and RAL, and a 2 × 100 Polar RP column for TFV/FTC/3TC. Mobile phase was methanol:water:formic acid (70:30:0.1, v/v/v) for ATV, DRV, DTG, EFV and RTV (10 uL injection, flow rate: 1.00 mL/min), ACN:water:formic acid (35:65:0.1, v/v/v) for RAL (50 uL injection, flow rate: 1.00 mL/min), ACN:water:formic acid (2:98:0.1, v/v/v) for TFV, FTC and 3TC (50 uL injection, flow rate: 0.35 mL/min). Column temperature was 40° C across all assays. The mass spectrometer was operated in positive, multiple-reaction-monitoring (MRM) mode with electrospray ionization (ESI) for all analytes with the exception of EFV, which was operated in negative, MRM mode with ESI. The assay was linear over the calibration range of 1 to 250 ng/mL for all analytes. The addition of 1% ammonium hydroxide in sample tubes overcame up to 44% negative bias in QC samples and allowed the methods to meet full validation criteria.
MeSH term(s)	Humans ; Anti-HIV Agents/therapeutic use ; Chromatography, Liquid/methods ; Methanol ; Adsorption ; Ammonium Hydroxide ; Tandem Mass Spectrometry/methods ; Anti-Retroviral Agents/analysis ; Tenofovir/therapeutic use ; Lamivudine/therapeutic use ; Emtricitabine/therapeutic use ; Benzoxazines/analysis ; Ritonavir/therapeutic use ; HIV Infections/drug therapy ; Water
Chemical Substances	formic acid (0YIW783RG1) ; Anti-HIV Agents ; Methanol (Y4S76JWI15) ; Ammonium Hydroxide (5138Q19F1X) ; Anti-Retroviral Agents ; Tenofovir (99YXE507IL) ; Lamivudine (2T8Q726O95) ; Emtricitabine (G70B4ETF4S) ; efavirenz (JE6H2O27P8) ; Benzoxazines ; Ritonavir (O3J8G9O825) ; Water (059QF0KO0R)
Language	English
Publishing date	2023-06-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2023.123810
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Article ; Online: A novel 4-cell in-vitro blood-brain barrier model and its characterization by confocal microscopy and TEER measurement.

Malik, Johid R / Fletcher, Courtney V / Podany, Anthony T / Dyavar, Shetty Ravi / Scarsi, Kimberly K / Pais, Gwendolyn M / Scheetz, Marc H / Avedissian, Sean N

Journal of neuroscience methods

2023 Volume 392, Page(s) 109867

Abstract: The blood-brain barrier (BBB) is a protective cellular anatomical layer with a dynamic micro-environment, tightly regulating the transport of materials across it. To achieve in-vivo characteristics, an in-vitro BBB model requires the constituent cell ... ...

Abstract	The blood-brain barrier (BBB) is a protective cellular anatomical layer with a dynamic micro-environment, tightly regulating the transport of materials across it. To achieve in-vivo characteristics, an in-vitro BBB model requires the constituent cell types to be layered in an appropriate order. A cost-effective in-vitro BBB model is desired to facilitate central nervous system (CNS) drug penetration studies. Enhanced integrity of tight junctions observed during the in-vitro BBB establishment and post-experiment is essential in these models. We successfully developed an in-vitro BBB model mimicking the in-vivo cell composition and a distinct order of seeding primary human brain cells. Unlike other in-vitro BBB models, our work avoids the need for pre-coated plates for cell adhesion and provides better cell visualization during the procedure. We found that using bovine collagen-I coating, followed by bovine fibronectin coating and poly-L-lysine coating, yields better adhesion and layering of cells on the transwell membrane compared to earlier reported use of collagen and poly-L-lysine only. Our results indicated better cell visibility and imaging with the polyester transwell membrane as well as point to a higher and more stable Trans Endothelial Electrical Resistance values in this plate. In addition, we found that the addition of zinc induced higher claudin 5 expressions in neuronal cells. Dolutegravir, a drug used in the treatment of HIV, is known to appear in moderate concentrations in the CNS. Thus, dolutegravir was used to assess the functionality of the final model and cells. Using primary cells and an in-house coating strategy substantially reduces costs and provides superior imaging of cells and their tight junction protein expression. Our 4-cell-based BBB model is a suitable experimental model for the drug screening process.
MeSH term(s)	Animals ; Cattle ; Humans ; Blood-Brain Barrier/physiology ; Cell Line ; Polylysine/metabolism ; Polylysine/pharmacology ; Endothelial Cells ; Microscopy, Confocal
Chemical Substances	Polylysine (25104-18-1)
Language	English
Publishing date	2023-04-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2023.109867
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Article ; Online: Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19

Zhou, Xiao-Jian / Horga, Arantxa / Puri, Adeep / Winchester, Lee / Montrond, Maureen / Pietropaolo, Keith / Belanger, Bruce / Fletcher, Courtney V. / Hammond, Janet

medRxiv

Abstract: Bemnifosbuvir (BEM, AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of patients with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at ... ...

Abstract	Bemnifosbuvir (BEM, AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of patients with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved. We conducted a Phase 1 study in healthy subjects to assess the bronchopulmonary pharmacokinetics, safety, and tolerability of repeated doses of BEM. A total of 24 subjects were assigned to receive twice-daily (BID) BEM at doses of 275, 550, or 825 mg for up to 3.5 days. AT-511, the free base of BEM, was largely eliminated from the plasma within 6 h post dose in all dosing groups. Antiviral drug levels of BEM were consistently achieved in the lungs with BEM 550 mg BID. The mean level of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, measured in the epithelial lining fluid of the lungs was 0.62 μM at 4-5 h post dose. This exceeded the target in vitro 90% effective concentration (EC90) of 0.5 μM for antiviral drug exposure against SARS-CoV-2 replication in human airway epithelial cells. BEM was well tolerated across all doses tested, and most treatment-emergent adverse events reported were mild in severity and resolved. The favorable pharmacokinetics and safety profile of BEM demonstrates its potential as an oral antiviral treatment for COVID-19, with 550 mg BEM BID currently under further clinical evaluation in patients with COVID-19.
Keywords	covid19
Language	English
Publishing date	2024-01-08
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2024.01.03.24300783
Database	COVID19

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Article ; Online: In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells.

Avedissian, Sean N / Malik, Johid R / Podany, Anthony T / Neely, Michael / Rhodes, Nathaniel J / Scarsi, Kimberly K / Scheetz, Marc H / Duryee, Michael J / Modebelu, Ukamaka O / Mykris, Timothy M / Winchester, Lee C / Byrareddy, Siddappa N / Fletcher, Courtney V

Scientific reports

2024 Volume 14, Issue 1, Page(s) 10709

Abstract: Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been ... ...

Abstract	Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC
MeSH term(s)	Animals ; Rats ; Ritonavir/pharmacokinetics ; SARS-CoV-2/drug effects ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/virology ; Humans ; Male ; Brain/metabolism ; Brain/virology ; COVID-19 Drug Treatment ; COVID-19/virology ; COVID-19/cerebrospinal fluid ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/pharmacology ; Rats, Sprague-Dawley ; Central Nervous System/metabolism ; Central Nervous System/virology
Chemical Substances	Ritonavir (O3J8G9O825) ; Antiviral Agents
Language	English
Publishing date	2024-05-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-60935-5
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Article ; Online: Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors: An Updated Review.

Podany, Anthony T / Scarsi, Kimberly K / Pham, Michelle M / Fletcher, Courtney V

Clinical pharmacokinetics

2020 Volume 59, Issue 9, Page(s) 1085–1107

Abstract: Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors. Integrase strand transfer ...

Abstract	Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors. Integrase strand transfer inhibitors are potent inhibitors of the HIV integrase enzyme with IC
Language	English
Publishing date	2020-05-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-020-00898-8
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Zs.A 1246: Show issues

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Article ; Online: Pharmacologic approaches to HIV-associated neurocognitive disorders.

Avedissian, Sean N / Dyavar, Shetty Ravi / Fox, Howard S / Fletcher, Courtney V

Current opinion in pharmacology

2020 Volume 54, Page(s) 102–108

Abstract: Antiretroviral therapy in people living with HIV can achieve potent, long-term suppression of HIV plasma viremia and has increased life expectancy. The central nervous system is infected early after virus acquisition and remains a reservoir for HIV. HIV- ... ...

Abstract	Antiretroviral therapy in people living with HIV can achieve potent, long-term suppression of HIV plasma viremia and has increased life expectancy. The central nervous system is infected early after virus acquisition and remains a reservoir for HIV. HIV-associated neurocognitive disorders (HAND) are an end-organ manifestation of HIV infection. The need to address neurological complications caused by HAND is significant as approximately 50% of people living with HIV on suppressive antiretroviral therapy are estimated to have some form of HAND. This review discusses the pathophysiology of HAND, CSF/CNS penetration and clinical pharmacology of antiretrovirals including pharmacokinetic/pharmacodynamic relationships, the persistence of HIV in the brain, and future therapeutic approaches to preserve and improve sustained viral suppression in the brain.
MeSH term(s)	Animals ; Anti-HIV Agents/pharmacokinetics ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Brain/metabolism ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV Infections/metabolism ; Humans ; Neurocognitive Disorders/drug therapy ; Neurocognitive Disorders/etiology ; Neurocognitive Disorders/metabolism
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2020-10-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2020.09.003
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