Abstract
The introduction, in 1995, of highly active antiretroviral therapy (HAART) dramatically reduced the morbidity and mortality of HIV-infected patients. However, the brain remains a site of viral replication for HIV and thus is still an important target for antiretroviral agents. Consequently, a clear understanding of how the current anti-HIV drugs reach the CNS, and interact at the level of the blood-brain barrier and blood-CSF barrier, is important if we are to maximise viral suppression and improve clinical outcome. It would also contribute to the development of new anti-HIV drugs and the identification of transport inhibitors that could be used as adjuvant therapies. In this review we focus on the role of the blood-brain and blood-CSF barriers in the delivery of the main classes of approved anti-HIV drugs. Among these groups, the CNS distribution of the nucleoside reverse transcriptase inhibitors is the best characterised. It involves probenecid efflux transport mechanisms, which limit their brain delivery and probably their, neurological efficacy. Nevirapine and efavirenz, the commonly prescribed non-nucleoside reverse transcriptase inhibitors, can readily enter the CSF, however, it remains to be seen if a transport system is involved in their distribution. The protease inhibitors have only a limited ability to reach the CNS, with the majority of this class of drugs not even being detected in human CSF after administration. This is partly the result of their removal from the CNS by the efflux transporters; P-glycoprotein, and possibly multi-drug resistance associated protein (MRP).
Keywords: blood-brain barrier, choroid plexus, hiv, transport, csf, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors,, protease inhibitors
Current Pharmaceutical Design
Title: Anti-HIV Drug Distribution to the Central Nervous System
Volume: 10 Issue: 12
Author(s): S. A. Thomas
Affiliation:
Keywords: blood-brain barrier, choroid plexus, hiv, transport, csf, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors,, protease inhibitors
Abstract: The introduction, in 1995, of highly active antiretroviral therapy (HAART) dramatically reduced the morbidity and mortality of HIV-infected patients. However, the brain remains a site of viral replication for HIV and thus is still an important target for antiretroviral agents. Consequently, a clear understanding of how the current anti-HIV drugs reach the CNS, and interact at the level of the blood-brain barrier and blood-CSF barrier, is important if we are to maximise viral suppression and improve clinical outcome. It would also contribute to the development of new anti-HIV drugs and the identification of transport inhibitors that could be used as adjuvant therapies. In this review we focus on the role of the blood-brain and blood-CSF barriers in the delivery of the main classes of approved anti-HIV drugs. Among these groups, the CNS distribution of the nucleoside reverse transcriptase inhibitors is the best characterised. It involves probenecid efflux transport mechanisms, which limit their brain delivery and probably their, neurological efficacy. Nevirapine and efavirenz, the commonly prescribed non-nucleoside reverse transcriptase inhibitors, can readily enter the CSF, however, it remains to be seen if a transport system is involved in their distribution. The protease inhibitors have only a limited ability to reach the CNS, with the majority of this class of drugs not even being detected in human CSF after administration. This is partly the result of their removal from the CNS by the efflux transporters; P-glycoprotein, and possibly multi-drug resistance associated protein (MRP).
Export Options
About this article
Cite this article as:
Thomas A. S., Anti-HIV Drug Distribution to the Central Nervous System, Current Pharmaceutical Design 2004; 10 (12) . https://dx.doi.org/10.2174/1381612043384835
DOI https://dx.doi.org/10.2174/1381612043384835 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Mitochondrial, Metabolic and Genotoxic Effects of Antiretroviral Nucleoside Reverse-Transcriptase Inhibitors
Anti-Infective Agents in Medicinal Chemistry Syphilis: An Epidemiological Review
Current Women`s Health Reviews Pharmacological Benefits of Active Components of Natural Products Against Traumatic Brain Injury - A Review
Current Pharmacogenomics and Personalized Medicine Interplay between Catalysts and Substrates for Activity of Class Ib Aminoacyl-tRNA Synthetases and Implications for Pharmacology
Current Topics in Medicinal Chemistry Use of Single Nucleotide Polymorphism Array Technology to Improve the Identification of Chromosomal Lesions in Leukemia
Current Cancer Drug Targets Thyroid Hormone Modulation of Immunity: Its Participation in Chronic Stress-Induced Immune Alterations
Current Immunology Reviews (Discontinued) Drug-Induced Peripheral Neuropathy: Diagnosis and Management
Current Cancer Drug Targets Content Based Medical Image Retrieval System Based on Generalized Gamma Distribution and Feature Matching Methodology
Current Medical Imaging Using Biologic Agents in Pediatric Rheumatologic Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Somatic Genomic Variations in Extra-Embryonic Tissues
Current Genomics Epidemiology of Candida albicans Infections and Role of Non-Candidaalbicans Yeasts
Current Drug Targets Meet the Editorial Board Member
Current Cancer Therapy Reviews Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy
Current Topics in Medicinal Chemistry Diabetes and Vascular Disease: Basic Concepts of Nitric Oxide Physiology, Endothelial Dysfunction, Oxidative Stress and Therapeutic Possibilities
Current Vascular Pharmacology Anti-Alzheimer Therapeutic Drugs Targeting γ-Secretase
Current Topics in Medicinal Chemistry Rationale and Prospects of Targeting Bacterial Two-component Systems for Antibacterial Treatment of Cystic Fibrosis Patients
Current Drug Targets Mutations of mtDNA in some Vascular and Metabolic Diseases
Current Pharmaceutical Design Microglia-Neuron Interaction in Inflammatory and Degenerative Diseases: Role of Cholinergic and Noradrenergic Systems
CNS & Neurological Disorders - Drug Targets Management of Acute and Chronic Open Wounds: The Importance of Moist Environment in Optimal Wound Healing
Current Pharmaceutical Biotechnology Molecular Subgrouping of Medulloblastoma: Impact Upon Research and Clinical Practice
Current Pediatric Reviews