Cargando…

CCR5 inhibitors: Emerging promising HIV therapeutic strategy

Though potent anti-HIV therapy has spectacularly reduced the morbidity and mortality of human immunodeficiency virus (HIV)-1 infection in the advanced countries, it continues to be associated with substantial toxicity, drug-drug interactions, difficulties in adherence, and abnormal cost. As a result...

Descripción completa

Detalles Bibliográficos
Autor principal: Rao, Padmasri Kutikuppala Surya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168031/
https://www.ncbi.nlm.nih.gov/pubmed/21938106
http://dx.doi.org/10.4103/2589-0557.55471
_version_ 1782211323165147136
author Rao, Padmasri Kutikuppala Surya
author_facet Rao, Padmasri Kutikuppala Surya
author_sort Rao, Padmasri Kutikuppala Surya
collection PubMed
description Though potent anti-HIV therapy has spectacularly reduced the morbidity and mortality of human immunodeficiency virus (HIV)-1 infection in the advanced countries, it continues to be associated with substantial toxicity, drug-drug interactions, difficulties in adherence, and abnormal cost. As a result, better effective, safe antiretroviral drugs and treatment strategies keep on to be pursued. In this process, CCR5 (chemokine receptor 5) inhibitors are a new class of antiretroviral drug used in the treatment of HIV. They are designed to prevent HIV infection of CD4 T-cells by blocking the CCR5. When the CCR5 receptor is unavailable, ‘R5-tropic’ HIV (the variant of the virus that is common in earlier HIV infection) cannot engage with a CD4 T-cell to infect the cell. In August 2007, the FDA approved the first chemokine (C-C motif) CCR5 inhibitor, maraviroc, for treatment-experienced patients infected with R5-using virus. Studies from different cohort in regions, affected by clad B HIV-1, demonstrate that 81-88% of HIV-1 variants in treatment naïve patients are CCR5 tropic and that virtually all the remaining variants are dual/mixed tropic i.e., are able to utilize both CCR5 and CXCR4 coreceptors. In treatment experienced patients, 49–78% of the variants are purely CCR5 tropic, 22–48% are dual/mixed tropic, and 2-5% exclusively utilize CXCR4. A 32 bp deletion in the CCR5 gene, which results in a frame shift and truncation of the normal CCR5 protein, was identified in a few persons who had remained uninfected after exposure to CCR5 tropic HIV-1 virus. This allele is common in white of European origin, with prevalence near to 10%, but is absent among East Asian, American Indian, Tamil Indian, and African ethnic groups. HIV-infected individuals, who are heterozygous for CCR5 delta 32, have slower rates of disease progression. The currently available data supports the continuation of the development of CCR5 antagonists in different settings related to HIV-1 infection. If safety issues do not emerge, these compounds could be positioned for use from very early stage of HIV infection to salvage strategies that would be an emerging therapeutic novel strategy for HIV/AIDS patients.
format Online
Article
Text
id pubmed-3168031
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Medknow Publications
record_format MEDLINE/PubMed
spelling pubmed-31680312011-09-21 CCR5 inhibitors: Emerging promising HIV therapeutic strategy Rao, Padmasri Kutikuppala Surya Indian J Sex Transm Dis AIDS Review Article Though potent anti-HIV therapy has spectacularly reduced the morbidity and mortality of human immunodeficiency virus (HIV)-1 infection in the advanced countries, it continues to be associated with substantial toxicity, drug-drug interactions, difficulties in adherence, and abnormal cost. As a result, better effective, safe antiretroviral drugs and treatment strategies keep on to be pursued. In this process, CCR5 (chemokine receptor 5) inhibitors are a new class of antiretroviral drug used in the treatment of HIV. They are designed to prevent HIV infection of CD4 T-cells by blocking the CCR5. When the CCR5 receptor is unavailable, ‘R5-tropic’ HIV (the variant of the virus that is common in earlier HIV infection) cannot engage with a CD4 T-cell to infect the cell. In August 2007, the FDA approved the first chemokine (C-C motif) CCR5 inhibitor, maraviroc, for treatment-experienced patients infected with R5-using virus. Studies from different cohort in regions, affected by clad B HIV-1, demonstrate that 81-88% of HIV-1 variants in treatment naïve patients are CCR5 tropic and that virtually all the remaining variants are dual/mixed tropic i.e., are able to utilize both CCR5 and CXCR4 coreceptors. In treatment experienced patients, 49–78% of the variants are purely CCR5 tropic, 22–48% are dual/mixed tropic, and 2-5% exclusively utilize CXCR4. A 32 bp deletion in the CCR5 gene, which results in a frame shift and truncation of the normal CCR5 protein, was identified in a few persons who had remained uninfected after exposure to CCR5 tropic HIV-1 virus. This allele is common in white of European origin, with prevalence near to 10%, but is absent among East Asian, American Indian, Tamil Indian, and African ethnic groups. HIV-infected individuals, who are heterozygous for CCR5 delta 32, have slower rates of disease progression. The currently available data supports the continuation of the development of CCR5 antagonists in different settings related to HIV-1 infection. If safety issues do not emerge, these compounds could be positioned for use from very early stage of HIV infection to salvage strategies that would be an emerging therapeutic novel strategy for HIV/AIDS patients. Medknow Publications 2009 /pmc/articles/PMC3168031/ /pubmed/21938106 http://dx.doi.org/10.4103/2589-0557.55471 Text en Copyright: © Indian Journal of Sexually Transmitted Diseases and AIDS http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Rao, Padmasri Kutikuppala Surya
CCR5 inhibitors: Emerging promising HIV therapeutic strategy
title CCR5 inhibitors: Emerging promising HIV therapeutic strategy
title_full CCR5 inhibitors: Emerging promising HIV therapeutic strategy
title_fullStr CCR5 inhibitors: Emerging promising HIV therapeutic strategy
title_full_unstemmed CCR5 inhibitors: Emerging promising HIV therapeutic strategy
title_short CCR5 inhibitors: Emerging promising HIV therapeutic strategy
title_sort ccr5 inhibitors: emerging promising hiv therapeutic strategy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168031/
https://www.ncbi.nlm.nih.gov/pubmed/21938106
http://dx.doi.org/10.4103/2589-0557.55471
work_keys_str_mv AT raopadmasrikutikuppalasurya ccr5inhibitorsemergingpromisinghivtherapeuticstrategy