Impact of antiretroviral treatment containing tenofovir difumarate on the telomere length of aviremic HIV-infected patients
OBJECTIVE:To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro. DESIGN:Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) MethodsTelomere length in who...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2017-09, Vol.76 (1), p.102-109 |
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| creator | Montejano, Rocio Stella-Ascariz, Natalia Monge, Susana Bernardino, José I Pérez-Valero, Ignacio Montes, MaLuisa Valencia, Eulalia Martín-Carbonero, Luz Moreno, Victoria González-García, Juan Arnalich, Francisco Mingorance, Jesús Berniches, Laura Pintado Perona, Rosario Arribas, José R |
| description | OBJECTIVE:To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro.
DESIGN:Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) MethodsTelomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders
RESULTS:200 patients included, 72% male, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing ART regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis significant predictors of shorter telomere length were older age (p = 0.008), parental age at birth (p = 0.038), Caucasian race (p = 0.048) and longer time of known HIV infection (10-20 years and ≥20 years compared with |
| doi_str_mv | 10.1097/QAI.0000000000001391 |
| format | Article |
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DESIGN:Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) MethodsTelomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders
RESULTS:200 patients included, 72% male, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing ART regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis significant predictors of shorter telomere length were older age (p = 0.008), parental age at birth (p = 0.038), Caucasian race (p = 0.048) and longer time of known HIV infection (10-20 years and ≥20 years compared with <10 years, p = 0.003 and p = 0.056 respectively). There was no association between TDF exposure and telomere length after adjusting for possible confounding factors (age, parental age at birth, race and time of HIV infection). Total time receiving ART and duration of treatment with nucleoside reverse transcriptase inhibitors were associated with shorter telomere length but these associations were explained by time of known HIV infection
CONCLUSIONS:Our data do not suggest that telomerase activity inhibition caused by TDF in vitro, leads to telomere shortening in peripheral blood of HIV infected patients.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0000000000001391</identifier><identifier>PMID: 28418989</identifier><language>eng</language><publisher>United States: Copyright Wolters Kluwer Health, Inc. All rights reserved</publisher><subject>Age ; Aging - drug effects ; AIDS/HIV ; Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Birth ; Cross-Sectional Studies ; Exposure ; Female ; HIV ; HIV Infections - drug therapy ; HIV Infections - pathology ; HIV Infections - virology ; HIV-1 - physiology ; Human immunodeficiency virus ; Humans ; Impact analysis ; In vitro methods and tests ; Infections ; Male ; Middle Aged ; Molecules ; Multivariate analysis ; Nucleoside reverse transcriptase inhibitors ; Patients ; Peripheral blood ; Polymerase chain reaction ; Race ; Ribonucleic acid ; RNA ; RNA-directed DNA polymerase ; Spain - epidemiology ; Telomerase ; Telomerase - antagonists & inhibitors ; Telomere - drug effects ; Tenofovir ; Tenofovir - pharmacology ; Tenofovir - therapeutic use ; Treatment Outcome ; Viral Load</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2017-09, Vol.76 (1), p.102-109</ispartof><rights>Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.</rights><rights>Copyright Lippincott Williams & Wilkins Sep 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4301-bc0aff545b89a2f17a5786886ec3a196f0a1023c659a52a45681c1769e7efa2e3</citedby><cites>FETCH-LOGICAL-c4301-bc0aff545b89a2f17a5786886ec3a196f0a1023c659a52a45681c1769e7efa2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28418989$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Montejano, Rocio</creatorcontrib><creatorcontrib>Stella-Ascariz, Natalia</creatorcontrib><creatorcontrib>Monge, Susana</creatorcontrib><creatorcontrib>Bernardino, José I</creatorcontrib><creatorcontrib>Pérez-Valero, Ignacio</creatorcontrib><creatorcontrib>Montes, MaLuisa</creatorcontrib><creatorcontrib>Valencia, Eulalia</creatorcontrib><creatorcontrib>Martín-Carbonero, Luz</creatorcontrib><creatorcontrib>Moreno, Victoria</creatorcontrib><creatorcontrib>González-García, Juan</creatorcontrib><creatorcontrib>Arnalich, Francisco</creatorcontrib><creatorcontrib>Mingorance, Jesús</creatorcontrib><creatorcontrib>Berniches, Laura Pintado</creatorcontrib><creatorcontrib>Perona, Rosario</creatorcontrib><creatorcontrib>Arribas, José R</creatorcontrib><title>Impact of antiretroviral treatment containing tenofovir difumarate on the telomere length of aviremic HIV-infected patients</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>OBJECTIVE:To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro.
DESIGN:Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) MethodsTelomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders
RESULTS:200 patients included, 72% male, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing ART regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis significant predictors of shorter telomere length were older age (p = 0.008), parental age at birth (p = 0.038), Caucasian race (p = 0.048) and longer time of known HIV infection (10-20 years and ≥20 years compared with <10 years, p = 0.003 and p = 0.056 respectively). There was no association between TDF exposure and telomere length after adjusting for possible confounding factors (age, parental age at birth, race and time of HIV infection). Total time receiving ART and duration of treatment with nucleoside reverse transcriptase inhibitors were associated with shorter telomere length but these associations were explained by time of known HIV infection
CONCLUSIONS:Our data do not suggest that telomerase activity inhibition caused by TDF in vitro, leads to telomere shortening in peripheral blood of HIV infected patients.</description><subject>Age</subject><subject>Aging - drug effects</subject><subject>AIDS/HIV</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Birth</subject><subject>Cross-Sectional Studies</subject><subject>Exposure</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Impact analysis</subject><subject>In vitro methods and tests</subject><subject>Infections</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecules</subject><subject>Multivariate analysis</subject><subject>Nucleoside reverse transcriptase inhibitors</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Polymerase chain reaction</subject><subject>Race</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA-directed DNA polymerase</subject><subject>Spain - epidemiology</subject><subject>Telomerase</subject><subject>Telomerase - antagonists & inhibitors</subject><subject>Telomere - drug effects</subject><subject>Tenofovir</subject><subject>Tenofovir - pharmacology</subject><subject>Tenofovir - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Viral Load</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFqFTEUhgdRbK2-gUjATTfTJjPJJFmWYu2FghTUbTg396Q3NZNck0yL-PKm3irShdkkkO__OJy_694yesKolqfXZ6sT-s9ho2bPukOmOe-lUvx5e4tB9JyN4qB7VcptYybO9cvuYFCcKa30YfdzNe_AVpIcgVh9xprTnc8QSM0IdcZYiU2xgo8-3pCKMbkHgGy8W2bIUJGkSOoW219IM2YkAeNN3f5WNhJnb8nl6mvvo0NbcUN2UH3zltfdCweh4JvH-6j7cvHh8_llf_Xp4-r87Kq3fKSsX1sKzgku1krD4JgEIdWk1IR2BKYnR4HRYbST0CAG4GJSzDI5aZToYMDxqDvee3c5fV-wVDP7YjEEiJiWYphSWspJ8aGh75-gt2nJsU1nmB6lpILysVF8T9mcSsnozC77towfhlHzUI5p5Zin5bTYu0f5sp5x8zf0p40GqD1wn0LFXL6F5R6z2SKEuv2_-xdO7Jx9</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Montejano, Rocio</creator><creator>Stella-Ascariz, Natalia</creator><creator>Monge, Susana</creator><creator>Bernardino, José I</creator><creator>Pérez-Valero, Ignacio</creator><creator>Montes, MaLuisa</creator><creator>Valencia, Eulalia</creator><creator>Martín-Carbonero, Luz</creator><creator>Moreno, Victoria</creator><creator>González-García, Juan</creator><creator>Arnalich, Francisco</creator><creator>Mingorance, Jesús</creator><creator>Berniches, Laura Pintado</creator><creator>Perona, Rosario</creator><creator>Arribas, José R</creator><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</general><general>Lippincott Williams & Wilkins Ovid Technologies</general><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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20170901</creationdate><title>Impact of antiretroviral treatment containing tenofovir difumarate on the telomere length of aviremic HIV-infected patients</title><author>Montejano, Rocio ; Stella-Ascariz, Natalia ; Monge, Susana ; Bernardino, José I ; Pérez-Valero, Ignacio ; Montes, MaLuisa ; Valencia, Eulalia ; Martín-Carbonero, Luz ; Moreno, Victoria ; González-García, Juan ; Arnalich, Francisco ; Mingorance, Jesús ; Berniches, Laura Pintado ; Perona, Rosario ; Arribas, José R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4301-bc0aff545b89a2f17a5786886ec3a196f0a1023c659a52a45681c1769e7efa2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Age</topic><topic>Aging - drug effects</topic><topic>AIDS/HIV</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Birth</topic><topic>Cross-Sectional Studies</topic><topic>Exposure</topic><topic>Female</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - pathology</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Impact analysis</topic><topic>In vitro methods and tests</topic><topic>Infections</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecules</topic><topic>Multivariate analysis</topic><topic>Nucleoside reverse transcriptase inhibitors</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Polymerase chain reaction</topic><topic>Race</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA-directed DNA polymerase</topic><topic>Spain - epidemiology</topic><topic>Telomerase</topic><topic>Telomerase - antagonists & inhibitors</topic><topic>Telomere - drug effects</topic><topic>Tenofovir</topic><topic>Tenofovir - pharmacology</topic><topic>Tenofovir - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Montejano, Rocio</creatorcontrib><creatorcontrib>Stella-Ascariz, Natalia</creatorcontrib><creatorcontrib>Monge, Susana</creatorcontrib><creatorcontrib>Bernardino, José I</creatorcontrib><creatorcontrib>Pérez-Valero, Ignacio</creatorcontrib><creatorcontrib>Montes, MaLuisa</creatorcontrib><creatorcontrib>Valencia, Eulalia</creatorcontrib><creatorcontrib>Martín-Carbonero, Luz</creatorcontrib><creatorcontrib>Moreno, Victoria</creatorcontrib><creatorcontrib>González-García, Juan</creatorcontrib><creatorcontrib>Arnalich, Francisco</creatorcontrib><creatorcontrib>Mingorance, Jesús</creatorcontrib><creatorcontrib>Berniches, Laura Pintado</creatorcontrib><creatorcontrib>Perona, Rosario</creatorcontrib><creatorcontrib>Arribas, José R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Montejano, Rocio</au><au>Stella-Ascariz, Natalia</au><au>Monge, Susana</au><au>Bernardino, José I</au><au>Pérez-Valero, Ignacio</au><au>Montes, MaLuisa</au><au>Valencia, Eulalia</au><au>Martín-Carbonero, Luz</au><au>Moreno, Victoria</au><au>González-García, Juan</au><au>Arnalich, Francisco</au><au>Mingorance, Jesús</au><au>Berniches, Laura Pintado</au><au>Perona, Rosario</au><au>Arribas, José R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of antiretroviral treatment containing tenofovir difumarate on the telomere length of aviremic HIV-infected patients</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>76</volume><issue>1</issue><spage>102</spage><epage>109</epage><pages>102-109</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><abstract>OBJECTIVE:To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro.
DESIGN:Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) MethodsTelomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders
RESULTS:200 patients included, 72% male, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing ART regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis significant predictors of shorter telomere length were older age (p = 0.008), parental age at birth (p = 0.038), Caucasian race (p = 0.048) and longer time of known HIV infection (10-20 years and ≥20 years compared with <10 years, p = 0.003 and p = 0.056 respectively). There was no association between TDF exposure and telomere length after adjusting for possible confounding factors (age, parental age at birth, race and time of HIV infection). Total time receiving ART and duration of treatment with nucleoside reverse transcriptase inhibitors were associated with shorter telomere length but these associations were explained by time of known HIV infection
CONCLUSIONS:Our data do not suggest that telomerase activity inhibition caused by TDF in vitro, leads to telomere shortening in peripheral blood of HIV infected patients.</abstract><cop>United States</cop><pub>Copyright Wolters Kluwer Health, Inc. All rights reserved</pub><pmid>28418989</pmid><doi>10.1097/QAI.0000000000001391</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of acquired immune deficiency syndromes (1999), 2017-09, Vol.76 (1), p.102-109 |
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| source | Freely Accessible Journals; MEDLINE; Journals@Ovid LWW Legacy Archive; Journals@Ovid Complete |
| subjects | Age Aging - drug effects AIDS/HIV Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Birth Cross-Sectional Studies Exposure Female HIV HIV Infections - drug therapy HIV Infections - pathology HIV Infections - virology HIV-1 - physiology Human immunodeficiency virus Humans Impact analysis In vitro methods and tests Infections Male Middle Aged Molecules Multivariate analysis Nucleoside reverse transcriptase inhibitors Patients Peripheral blood Polymerase chain reaction Race Ribonucleic acid RNA RNA-directed DNA polymerase Spain - epidemiology Telomerase Telomerase - antagonists & inhibitors Telomere - drug effects Tenofovir Tenofovir - pharmacology Tenofovir - therapeutic use Treatment Outcome Viral Load |
| title | Impact of antiretroviral treatment containing tenofovir difumarate on the telomere length of aviremic HIV-infected patients |
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