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Adjuvant therapies for HIV-associated neurocognitive disorders
OBJECTIVE: HIV-associated neurocognitive disorder (HAND) is a frequent and heterogeneous complication of HIV, affecting nearly 50% of infected individuals in the combined antiretroviral therapy (cART) era. This is a particularly devastating statistic because the diagnosis of HAND confers an increase...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265066/ https://www.ncbi.nlm.nih.gov/pubmed/25540809 http://dx.doi.org/10.1002/acn3.131 |
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author | McGuire, Jennifer L Barrett, Jeffrey S Vezina, Heather E Spitsin, Sergei Douglas, Steven D |
author_facet | McGuire, Jennifer L Barrett, Jeffrey S Vezina, Heather E Spitsin, Sergei Douglas, Steven D |
author_sort | McGuire, Jennifer L |
collection | PubMed |
description | OBJECTIVE: HIV-associated neurocognitive disorder (HAND) is a frequent and heterogeneous complication of HIV, affecting nearly 50% of infected individuals in the combined antiretroviral therapy (cART) era. This is a particularly devastating statistic because the diagnosis of HAND confers an increased risk of HIV-associated morbidity and mortality in affected patients. While cART is helpful in the treatment of the more severe forms of HAND, there is a therapeutic gap in the milder forms of HAND, where cART is less effective. Multiple adjuvant therapies with various mechanisms of action have been studied (N-methyl D-aspartate [NMDA]-receptor antagonists, MAO-B inhibitors, tetracycline-class antibiotics, and others), but none have shown a clear positive effect in HAND. While this lack of efficacy may be because the appropriate therapeutic targets have not yet been determined, we aimed to discuss that study results may also influenced by clinical trial design. METHODS: This report is a systematic review of clinical trials of adjuvant therapies for HAND performed from January 1996 through June 2014. RESULTS: Possible drawbacks in study design, including lack of standardized case definitions, poorly defined target populations, inappropriate dose selection and measurable outcomes, and brief study durations may have masked true underlying mechanistic effects of previously investigated adjuvant therapies for HAND in specific patient populations. CONCLUSIONS: A proposal for streamlining and maximizing the likelihood of success in future clinical studies using a ‘learning and confirming’ investigational paradigm, incorporating stronger adaptive Phase I/II study designs, computerized modeling, and population/goal of treatment-specific Phase III clinical trials is presented. |
format | Online Article Text |
id | pubmed-4265066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42650662014-12-24 Adjuvant therapies for HIV-associated neurocognitive disorders McGuire, Jennifer L Barrett, Jeffrey S Vezina, Heather E Spitsin, Sergei Douglas, Steven D Ann Clin Transl Neurol Review Article OBJECTIVE: HIV-associated neurocognitive disorder (HAND) is a frequent and heterogeneous complication of HIV, affecting nearly 50% of infected individuals in the combined antiretroviral therapy (cART) era. This is a particularly devastating statistic because the diagnosis of HAND confers an increased risk of HIV-associated morbidity and mortality in affected patients. While cART is helpful in the treatment of the more severe forms of HAND, there is a therapeutic gap in the milder forms of HAND, where cART is less effective. Multiple adjuvant therapies with various mechanisms of action have been studied (N-methyl D-aspartate [NMDA]-receptor antagonists, MAO-B inhibitors, tetracycline-class antibiotics, and others), but none have shown a clear positive effect in HAND. While this lack of efficacy may be because the appropriate therapeutic targets have not yet been determined, we aimed to discuss that study results may also influenced by clinical trial design. METHODS: This report is a systematic review of clinical trials of adjuvant therapies for HAND performed from January 1996 through June 2014. RESULTS: Possible drawbacks in study design, including lack of standardized case definitions, poorly defined target populations, inappropriate dose selection and measurable outcomes, and brief study durations may have masked true underlying mechanistic effects of previously investigated adjuvant therapies for HAND in specific patient populations. CONCLUSIONS: A proposal for streamlining and maximizing the likelihood of success in future clinical studies using a ‘learning and confirming’ investigational paradigm, incorporating stronger adaptive Phase I/II study designs, computerized modeling, and population/goal of treatment-specific Phase III clinical trials is presented. BlackWell Publishing Ltd 2014-11 2014-10-23 /pmc/articles/PMC4265066/ /pubmed/25540809 http://dx.doi.org/10.1002/acn3.131 Text en © 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Review Article McGuire, Jennifer L Barrett, Jeffrey S Vezina, Heather E Spitsin, Sergei Douglas, Steven D Adjuvant therapies for HIV-associated neurocognitive disorders |
title | Adjuvant therapies for HIV-associated neurocognitive disorders |
title_full | Adjuvant therapies for HIV-associated neurocognitive disorders |
title_fullStr | Adjuvant therapies for HIV-associated neurocognitive disorders |
title_full_unstemmed | Adjuvant therapies for HIV-associated neurocognitive disorders |
title_short | Adjuvant therapies for HIV-associated neurocognitive disorders |
title_sort | adjuvant therapies for hiv-associated neurocognitive disorders |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265066/ https://www.ncbi.nlm.nih.gov/pubmed/25540809 http://dx.doi.org/10.1002/acn3.131 |
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