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The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time : evidence from the Delta trial
Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI). A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individua...
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| Published in: | Antiviral therapy 2008-01, Vol.13 (2), p.289-295 |
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| creator | ARENAS-PINTO, Alejandro BHASKARAN, Krishnan DUNN, David WELLER, Lan V. D |
| description | Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI).
A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individuals receiving zidovudine (AZT) alone or in combination with didanosine (ddl) or zalcitabine (ddC). In an on-treatment analysis, changes in the incidence of PN by duration of treatment were directly estimated using a flexible parametric survival model.
A total of 3,195 patients (total follow-up 4,593 person-years) were included in the analysis. AZT+ddC was associated with a higher incidence of PN (6.2 cases/100 person-years) compared with AZT monotherapy (3.0 cases/100 person-years) and AZT+ddl (2.2 cases/100 person-years). The risk of PN peaked around day 90 following randomization (at 8.9 events/100 person-years in the AZT+ddC arm). PN was also associated with age at entry (hazard ratio (HR)=2.35 for those aged 35-44 years compared with |
| doi_str_mv | 10.1177/135965350801300203 |
| format | article |
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A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individuals receiving zidovudine (AZT) alone or in combination with didanosine (ddl) or zalcitabine (ddC). In an on-treatment analysis, changes in the incidence of PN by duration of treatment were directly estimated using a flexible parametric survival model.
A total of 3,195 patients (total follow-up 4,593 person-years) were included in the analysis. AZT+ddC was associated with a higher incidence of PN (6.2 cases/100 person-years) compared with AZT monotherapy (3.0 cases/100 person-years) and AZT+ddl (2.2 cases/100 person-years). The risk of PN peaked around day 90 following randomization (at 8.9 events/100 person-years in the AZT+ddC arm). PN was also associated with age at entry (hazard ratio (HR)=2.35 for those aged 35-44 years compared with <30) and current CD4+ T-cell count (HR=2.27 for CD4+ T-cell counts <150 cell/mm3 compared with >350).
Our findings challenge the common supposition that PN arises from cumulative exposure to NRTIs. We found that patients who developed PN tended to do so shortly after exposure to antiretroviral therapy. Therefore, our results support the hypothesis of a susceptibility in a subgroup of patients. These results will be of direct interest to those working in resource-limited countries where potentially neurotoxic dideoxynucleosides are still widely used.</description><identifier>ISSN: 1359-6535</identifier><identifier>EISSN: 2040-2058</identifier><identifier>DOI: 10.1177/135965350801300203</identifier><identifier>PMID: 18505180</identifier><language>eng</language><publisher>London: International Medical Press</publisher><subject>Adult ; Anti-HIV Agents - adverse effects ; Anti-HIV Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Didanosine - adverse effects ; Didanosine - therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV Infections - virology ; Human immunodeficiency virus ; Humans ; Incidence ; Male ; Medical sciences ; Middle Aged ; Peripheral Nervous System Diseases - chemically induced ; Peripheral Nervous System Diseases - epidemiology ; Pharmacology. Drug treatments ; Reverse Transcriptase Inhibitors - adverse effects ; Reverse Transcriptase Inhibitors - therapeutic use ; Risk Factors ; Time Factors ; Zalcitabine - adverse effects ; Zalcitabine - therapeutic use ; Zidovudine - adverse effects ; Zidovudine - therapeutic use</subject><ispartof>Antiviral therapy, 2008-01, Vol.13 (2), p.289-295</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-6f30783471950298f0dc92336864ad8cc1417da3b5e717d12c6e8b0e0833d6803</citedby><cites>FETCH-LOGICAL-c406t-6f30783471950298f0dc92336864ad8cc1417da3b5e717d12c6e8b0e0833d6803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20262917$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18505180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ARENAS-PINTO, Alejandro</creatorcontrib><creatorcontrib>BHASKARAN, Krishnan</creatorcontrib><creatorcontrib>DUNN, David</creatorcontrib><creatorcontrib>WELLER, Lan V. D</creatorcontrib><title>The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time : evidence from the Delta trial</title><title>Antiviral therapy</title><addtitle>Antivir Ther</addtitle><description>Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI).
A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individuals receiving zidovudine (AZT) alone or in combination with didanosine (ddl) or zalcitabine (ddC). In an on-treatment analysis, changes in the incidence of PN by duration of treatment were directly estimated using a flexible parametric survival model.
A total of 3,195 patients (total follow-up 4,593 person-years) were included in the analysis. AZT+ddC was associated with a higher incidence of PN (6.2 cases/100 person-years) compared with AZT monotherapy (3.0 cases/100 person-years) and AZT+ddl (2.2 cases/100 person-years). The risk of PN peaked around day 90 following randomization (at 8.9 events/100 person-years in the AZT+ddC arm). PN was also associated with age at entry (hazard ratio (HR)=2.35 for those aged 35-44 years compared with <30) and current CD4+ T-cell count (HR=2.27 for CD4+ T-cell counts <150 cell/mm3 compared with >350).
Our findings challenge the common supposition that PN arises from cumulative exposure to NRTIs. We found that patients who developed PN tended to do so shortly after exposure to antiretroviral therapy. Therefore, our results support the hypothesis of a susceptibility in a subgroup of patients. These results will be of direct interest to those working in resource-limited countries where potentially neurotoxic dideoxynucleosides are still widely used.</description><subject>Adult</subject><subject>Anti-HIV Agents - adverse effects</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Didanosine - adverse effects</subject><subject>Didanosine - therapeutic use</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - virology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Incidence</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Peripheral Nervous System Diseases - chemically induced</subject><subject>Peripheral Nervous System Diseases - epidemiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Reverse Transcriptase Inhibitors - adverse effects</subject><subject>Reverse Transcriptase Inhibitors - therapeutic use</subject><subject>Risk Factors</subject><subject>Time Factors</subject><subject>Zalcitabine - adverse effects</subject><subject>Zalcitabine - therapeutic use</subject><subject>Zidovudine - adverse effects</subject><subject>Zidovudine - therapeutic use</subject><issn>1359-6535</issn><issn>2040-2058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNplkc9O3DAQh62KqixLX4BD5QvcUsZ2_ji9oaWlSCv1AufIsSddUydObQdpn6SvW69YwYHTeKzv-2k0Q8gFg6-MNc01E1VbV6ICCUwAcBAfyIpDCQWHSp6Q1QEoDsQpOYvxKSOyBfhETpmsoGISVuTfww5psPEP9QM1-IzOz3b6TWcMdt5hUI5OuAQ_q7TbUzuZRaOh_Z5Oi3boozVZz1qISFNQU9TZSyp3dtrZ3iYfYs7VAfNfpD6TNNkR6TeKz1meNNIh-JGmPMctuqRyjFXunHwclIv4-VjX5PHH94fNz2L76-5-c7MtdAl1KupBQCNF2bC2At7KAYxuuRC1rEtlpNasZI1Roq-wyQ_GdY2yBwQphKkliDW5esmdg_-7YEzdaKNG59SEfokdZ1xC05YZ5C-gDj7GgEM3BzuqsO8YdIdzdO_PkaUvx_SlH9G8Kcf9Z-DyCKiolRvyBrWNrxwHXvOWNeI_D_GUGw</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>ARENAS-PINTO, Alejandro</creator><creator>BHASKARAN, Krishnan</creator><creator>DUNN, David</creator><creator>WELLER, Lan V. D</creator><general>International Medical Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20080101</creationdate><title>The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time : evidence from the Delta trial</title><author>ARENAS-PINTO, Alejandro ; BHASKARAN, Krishnan ; DUNN, David ; WELLER, Lan V. D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-6f30783471950298f0dc92336864ad8cc1417da3b5e717d12c6e8b0e0833d6803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Anti-HIV Agents - adverse effects</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Didanosine - adverse effects</topic><topic>Didanosine - therapeutic use</topic><topic>Double-Blind Method</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - virology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Incidence</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Peripheral Nervous System Diseases - chemically induced</topic><topic>Peripheral Nervous System Diseases - epidemiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Reverse Transcriptase Inhibitors - adverse effects</topic><topic>Reverse Transcriptase Inhibitors - therapeutic use</topic><topic>Risk Factors</topic><topic>Time Factors</topic><topic>Zalcitabine - adverse effects</topic><topic>Zalcitabine - therapeutic use</topic><topic>Zidovudine - adverse effects</topic><topic>Zidovudine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ARENAS-PINTO, Alejandro</creatorcontrib><creatorcontrib>BHASKARAN, Krishnan</creatorcontrib><creatorcontrib>DUNN, David</creatorcontrib><creatorcontrib>WELLER, Lan V. D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Antiviral therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ARENAS-PINTO, Alejandro</au><au>BHASKARAN, Krishnan</au><au>DUNN, David</au><au>WELLER, Lan V. D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time : evidence from the Delta trial</atitle><jtitle>Antiviral therapy</jtitle><addtitle>Antivir Ther</addtitle><date>2008-01-01</date><risdate>2008</risdate><volume>13</volume><issue>2</issue><spage>289</spage><epage>295</epage><pages>289-295</pages><issn>1359-6535</issn><eissn>2040-2058</eissn><abstract>Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI).
A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individuals receiving zidovudine (AZT) alone or in combination with didanosine (ddl) or zalcitabine (ddC). In an on-treatment analysis, changes in the incidence of PN by duration of treatment were directly estimated using a flexible parametric survival model.
A total of 3,195 patients (total follow-up 4,593 person-years) were included in the analysis. AZT+ddC was associated with a higher incidence of PN (6.2 cases/100 person-years) compared with AZT monotherapy (3.0 cases/100 person-years) and AZT+ddl (2.2 cases/100 person-years). The risk of PN peaked around day 90 following randomization (at 8.9 events/100 person-years in the AZT+ddC arm). PN was also associated with age at entry (hazard ratio (HR)=2.35 for those aged 35-44 years compared with <30) and current CD4+ T-cell count (HR=2.27 for CD4+ T-cell counts <150 cell/mm3 compared with >350).
Our findings challenge the common supposition that PN arises from cumulative exposure to NRTIs. We found that patients who developed PN tended to do so shortly after exposure to antiretroviral therapy. Therefore, our results support the hypothesis of a susceptibility in a subgroup of patients. These results will be of direct interest to those working in resource-limited countries where potentially neurotoxic dideoxynucleosides are still widely used.</abstract><cop>London</cop><pub>International Medical Press</pub><pmid>18505180</pmid><doi>10.1177/135965350801300203</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Anti-HIV Agents - adverse effects Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Didanosine - adverse effects Didanosine - therapeutic use Double-Blind Method Drug Therapy, Combination Female HIV Infections - complications HIV Infections - drug therapy HIV Infections - virology Human immunodeficiency virus Humans Incidence Male Medical sciences Middle Aged Peripheral Nervous System Diseases - chemically induced Peripheral Nervous System Diseases - epidemiology Pharmacology. Drug treatments Reverse Transcriptase Inhibitors - adverse effects Reverse Transcriptase Inhibitors - therapeutic use Risk Factors Time Factors Zalcitabine - adverse effects Zalcitabine - therapeutic use Zidovudine - adverse effects Zidovudine - therapeutic use |
| title | The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time : evidence from the Delta trial |
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