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
Advances in the Molecular Pathogenesis of Inflammatory Bowel Disease.
This thematic issue will emphasize the recent breakthroughs in the mechanisms of Inflammatory bowel disease (IBD) pathogenesis and devotes some understanding of both Crohn’s and ulcerative colitis. It is expected to include studies about cellular and genetic aspects, which help to precipitate the disease, and the immune system-gut microbiome relations ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
-
Role of Caspases in Activation-Induced Cell Death of Neuroglia
Current Enzyme Inhibition Nicotinic Receptors Containing the α7 Subunit: A Model for Rational Drug Design
Current Medicinal Chemistry A Step Further Towards Multitarget Drugs for Alzheimer and Neuronal Vascular Diseases: Targeting the Cholinergic System, Amyloid-β Aggregation and Ca2++ Dyshomeostasis
Current Medicinal Chemistry Hereditary Parkinsonism-Associated Genetic Variations in PARK9 Locus Lead to Functional Impairment of ATPase Type 13A2
Current Protein & Peptide Science Human Immunodeficiency Virus-Mononuclear Phagocyte Interactions:Emerging Avenues of Biomarker Discovery, Modes of Viral Persistence and Disease Pathogenesis
Current HIV Research Epidemiology and Prevention of Bacterial Infections in Patients with Hematologic Malignancies
Infectious Disorders - Drug Targets Drug Combinations Enhancing the Antineoplastic Effects of Erlotinib in High-Grade Glioma
Recent Patents on Anti-Cancer Drug Discovery Targeted Therapy for Glioblastoma: Lessons Learned and Future Directions
Current Cancer Therapy Reviews Emerging Therapeutic Approaches Based on Nanotechnology for the Treatment of Diseases Associated with Telomere Dysfunction
Mini-Reviews in Medicinal Chemistry Gene Therapy and Targeted Toxins for Glioma
Current Gene Therapy Capillary Electrophoresis Interfaced with a Mass Spectrometer (CE-MS): Technical Considerations and Applicability for Biomarker Studies in Animals
Current Protein & Peptide Science Steroid Biosynthesis Inhibitors in the Therapy of Hypercortisolism: Theory and Practice
Current Medicinal Chemistry Alzheimer’s Disease-related Biomarkers in Aging Adults with Down Syndrome: Systematic Review
Current Psychiatry Research and Reviews Role of Long Non-coding RNAs in the Pathogenesis of Alzheimer’s and Parkinson’s Diseases
Current Aging Science Effectiveness of Resveratrol Against Cardiovascular Disease
Mini-Reviews in Organic Chemistry Metabolomics as a Functional Tool in Screening Gastro Intestinal Diseases: Where are we in High Throughput Screening?
Combinatorial Chemistry & High Throughput Screening Editorial [Hot Topic: Neurodegenerative Diseases (Guest Editor: Santosh R. DMello)]
Current Drug Targets - CNS & Neurological Disorders The Role of Neurotrophins in Axonal Growth, Guidance, and Regeneration
Current Neurovascular Research Epstein-Barr Virus-associated Gastric Cancer and Potential Mechanisms of Oncogenesis
Current Cancer Drug Targets Amyloid-Beta Protein Clearance and Degradation (ABCD) Pathways and their Role in Alzheimer's Disease
Current Alzheimer Research