Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy
BACKGROUND:Several studies reported an association between immunodeficiency and non–AIDS-defining diseases. We investigated whether nonstructured treatment interruptions and episodes of viremia during suppressive combination antiretroviral therapy were independently associated with non-AIDS diseases...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2012-07, Vol.60 (3), p.265-272 |
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| container_title | Journal of acquired immune deficiency syndromes (1999) |
| container_volume | 60 |
| creator | Zhang, Shuangjie van Sighem, Ard Kesselring, Anouk Gras, Luuk Smit, Colette Prins, Jan M Kauffmann, Robert Richter, Clemens de Wolf, Frank Reiss, Peter |
| description | BACKGROUND:Several studies reported an association between immunodeficiency and non–AIDS-defining diseases. We investigated whether nonstructured treatment interruptions and episodes of viremia during suppressive combination antiretroviral therapy were independently associated with non-AIDS diseases.
METHODS:Six thousand four hundred forty patients with viral suppression (400), and serious non-AIDS diseases (cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis) were investigated by including time-updated cumulative exposure to either viremia and interruptions or HIV RNA >400 copies per milliliter.
RESULTS:During 24,603 person-years, of which 88.5% occurred during viral suppression, 102 patients developed cardiovascular disease, 54 chronic renal failure, and 70 liver fibrosis/cirrhosis. Overall incidence of non-AIDS diseases ranged from 1.41 (95% confidence interval0.73 to 2.46) per 100 person-years for CD4 counts 400 versus ≤400 copies per milliliter were 1.32 (1.01 to 1.73) for cardiovascular disease, 1.13 (0.66 to 1.92) for renal failure, and 0.86 (0.51 to 1.44) for fibrosis/cirrhosis.
CONCLUSIONS:Lower CD4 counts are associated with increased risk of non-AIDS diseases, whereas high-level viremia seems to be independently associated with cardiovascular disease. However, the power to detect associations with viremia or interruptions may have been limited as most events occurred during viral suppression. |
| doi_str_mv | 10.1097/QAI.0b013e318258c651 |
| format | Article |
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METHODS:Six thousand four hundred forty patients with viral suppression (<50 copies/mL) within 48 weeks of starting combination antiretroviral therapy were selected from the Dutch ATHENA cohort. In proportional hazards models, associations between treatment interruptions, viral suppression, low-level (50–400 copies/mL), and high-level viremia (>400), and serious non-AIDS diseases (cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis) were investigated by including time-updated cumulative exposure to either viremia and interruptions or HIV RNA >400 copies per milliliter.
RESULTS:During 24,603 person-years, of which 88.5% occurred during viral suppression, 102 patients developed cardiovascular disease, 54 chronic renal failure, and 70 liver fibrosis/cirrhosis. Overall incidence of non-AIDS diseases ranged from 1.41 (95% confidence interval0.73 to 2.46) per 100 person-years for CD4 counts <200 to 0.71 (0.49 to 1.00) for CD4 ≥500 cells per cubic millimeter. Compared with viral suppression, high-level viremia was associated only with cardiovascular disease (relative hazard1.37, 1.04 to 1.81 per year longer), whereas interruptions and low-level viremia were not associated with non-AIDS diseases. Relative hazards for cumulative exposure to RNA >400 versus ≤400 copies per milliliter were 1.32 (1.01 to 1.73) for cardiovascular disease, 1.13 (0.66 to 1.92) for renal failure, and 0.86 (0.51 to 1.44) for fibrosis/cirrhosis.
CONCLUSIONS:Lower CD4 counts are associated with increased risk of non-AIDS diseases, whereas high-level viremia seems to be independently associated with cardiovascular disease. However, the power to detect associations with viremia or interruptions may have been limited as most events occurred during viral suppression.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0b013e318258c651</identifier><identifier>PMID: 22531756</identifier><identifier>CODEN: JDSRET</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Adult ; AIDS/HIV ; Anti-HIV Agents - administration & dosage ; Anti-HIV Agents - therapeutic use ; Antiretroviral drugs ; Biological and medical sciences ; Cardiovascular disease ; Cardiovascular Diseases - etiology ; CD4 Lymphocyte Count ; Cohort Studies ; Female ; Fundamental and applied biological sciences. Psychology ; Glycoproteins ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious diseases ; Liver Cirrhosis - etiology ; Male ; Medical sciences ; Microbiology ; Middle Aged ; Miscellaneous ; Netherlands ; Proportional Hazards Models ; Renal Insufficiency, Chronic - etiology ; Risk Factors ; RNA, Viral - blood ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral infections ; Viremia - drug therapy ; Viremia - immunology ; Viremia - virology ; Virology</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2012-07, Vol.60 (3), p.265-272</ispartof><rights>2012 Lippincott Williams & Wilkins, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Lippincott Williams & Wilkins Jul 1, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4931-cf9b5c0de344a11527e1ecb0ffa8299471416411c719cbe601652416706d91b93</citedby><cites>FETCH-LOGICAL-c4931-cf9b5c0de344a11527e1ecb0ffa8299471416411c719cbe601652416706d91b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26067551$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22531756$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Shuangjie</creatorcontrib><creatorcontrib>van Sighem, Ard</creatorcontrib><creatorcontrib>Kesselring, Anouk</creatorcontrib><creatorcontrib>Gras, Luuk</creatorcontrib><creatorcontrib>Smit, Colette</creatorcontrib><creatorcontrib>Prins, Jan M</creatorcontrib><creatorcontrib>Kauffmann, Robert</creatorcontrib><creatorcontrib>Richter, Clemens</creatorcontrib><creatorcontrib>de Wolf, Frank</creatorcontrib><creatorcontrib>Reiss, Peter</creatorcontrib><title>Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:Several studies reported an association between immunodeficiency and non–AIDS-defining diseases. We investigated whether nonstructured treatment interruptions and episodes of viremia during suppressive combination antiretroviral therapy were independently associated with non-AIDS diseases.
METHODS:Six thousand four hundred forty patients with viral suppression (<50 copies/mL) within 48 weeks of starting combination antiretroviral therapy were selected from the Dutch ATHENA cohort. In proportional hazards models, associations between treatment interruptions, viral suppression, low-level (50–400 copies/mL), and high-level viremia (>400), and serious non-AIDS diseases (cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis) were investigated by including time-updated cumulative exposure to either viremia and interruptions or HIV RNA >400 copies per milliliter.
RESULTS:During 24,603 person-years, of which 88.5% occurred during viral suppression, 102 patients developed cardiovascular disease, 54 chronic renal failure, and 70 liver fibrosis/cirrhosis. Overall incidence of non-AIDS diseases ranged from 1.41 (95% confidence interval0.73 to 2.46) per 100 person-years for CD4 counts <200 to 0.71 (0.49 to 1.00) for CD4 ≥500 cells per cubic millimeter. Compared with viral suppression, high-level viremia was associated only with cardiovascular disease (relative hazard1.37, 1.04 to 1.81 per year longer), whereas interruptions and low-level viremia were not associated with non-AIDS diseases. Relative hazards for cumulative exposure to RNA >400 versus ≤400 copies per milliliter were 1.32 (1.01 to 1.73) for cardiovascular disease, 1.13 (0.66 to 1.92) for renal failure, and 0.86 (0.51 to 1.44) for fibrosis/cirrhosis.
CONCLUSIONS:Lower CD4 counts are associated with increased risk of non-AIDS diseases, whereas high-level viremia seems to be independently associated with cardiovascular disease. However, the power to detect associations with viremia or interruptions may have been limited as most events occurred during viral suppression.</description><subject>Adult</subject><subject>AIDS/HIV</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral drugs</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - etiology</subject><subject>CD4 Lymphocyte Count</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycoproteins</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Liver Cirrhosis - etiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Middle Aged</subject><subject>Miscellaneous</subject><subject>Netherlands</subject><subject>Proportional Hazards Models</subject><subject>Renal Insufficiency, Chronic - etiology</subject><subject>Risk Factors</subject><subject>RNA, Viral - blood</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral infections</subject><subject>Viremia - drug therapy</subject><subject>Viremia - immunology</subject><subject>Viremia - virology</subject><subject>Virology</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkd1rFDEUxQdRbK3-ByIBEXyZmjv5mjwubbULxa_Wvg6ZzB023dlkmsy09L83664KfRCfbrj5ncM9nKJ4DfQYqFYfvi2Wx7SlwJBBXYnaSgFPikPQnJeqrvnT_BaVKDkwcVC8SOmGUpCc6-fFQVUJBkrIw2J9NroUOkwk9OR8eU2uXcSNM8T4jkwrJN9dWm__PgdfLpanl-TUJTQpC5wnX83k0E9Z7MnlPI4RU3J3SBZ-yjZTDHcumoFcrTCa8eFl8aw3Q8JX-3lU_Ph4dnVyXl58-bQ8WVyUlmsGpe11KyztkHFuIGdQCGhb2vemrrTmCnjOAWAVaNuizKlElVeKyk5Dq9lR8X7nO8ZwO2Oamo1LFofBeAxzaoAyLoUWkv0HWtWUSagho28foTdhjj4H2VIVV5xSnim-o2wMKUXsmzG6jYkPGWq2vTW5t-Zxb1n2Zm8-txvs_oh-F5WBd3vAJGuGPhpvXfrLSSqV-GVU77j7MEwY03qY7zE2KzTDtPr3DT8BgYCv2w</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Zhang, Shuangjie</creator><creator>van Sighem, Ard</creator><creator>Kesselring, Anouk</creator><creator>Gras, Luuk</creator><creator>Smit, Colette</creator><creator>Prins, Jan M</creator><creator>Kauffmann, Robert</creator><creator>Richter, Clemens</creator><creator>de Wolf, Frank</creator><creator>Reiss, Peter</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7U1</scope><scope>7U2</scope><scope>7X8</scope></search><sort><creationdate>20120701</creationdate><title>Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy</title><author>Zhang, Shuangjie ; van Sighem, Ard ; Kesselring, Anouk ; Gras, Luuk ; Smit, Colette ; Prins, Jan M ; Kauffmann, Robert ; Richter, Clemens ; de Wolf, Frank ; Reiss, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4931-cf9b5c0de344a11527e1ecb0ffa8299471416411c719cbe601652416706d91b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>AIDS/HIV</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretroviral drugs</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - etiology</topic><topic>CD4 Lymphocyte Count</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glycoproteins</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - virology</topic><topic>HIV-1</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Liver Cirrhosis - etiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Middle Aged</topic><topic>Miscellaneous</topic><topic>Netherlands</topic><topic>Proportional Hazards Models</topic><topic>Renal Insufficiency, Chronic - etiology</topic><topic>Risk Factors</topic><topic>RNA, Viral - blood</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral infections</topic><topic>Viremia - drug therapy</topic><topic>Viremia - immunology</topic><topic>Viremia - virology</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Shuangjie</creatorcontrib><creatorcontrib>van Sighem, Ard</creatorcontrib><creatorcontrib>Kesselring, Anouk</creatorcontrib><creatorcontrib>Gras, Luuk</creatorcontrib><creatorcontrib>Smit, Colette</creatorcontrib><creatorcontrib>Prins, Jan M</creatorcontrib><creatorcontrib>Kauffmann, Robert</creatorcontrib><creatorcontrib>Richter, Clemens</creatorcontrib><creatorcontrib>de Wolf, Frank</creatorcontrib><creatorcontrib>Reiss, Peter</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>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>Risk Abstracts</collection><collection>Safety Science and Risk</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>Zhang, Shuangjie</au><au>van Sighem, Ard</au><au>Kesselring, Anouk</au><au>Gras, Luuk</au><au>Smit, Colette</au><au>Prins, Jan M</au><au>Kauffmann, Robert</au><au>Richter, Clemens</au><au>de Wolf, Frank</au><au>Reiss, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>60</volume><issue>3</issue><spage>265</spage><epage>272</epage><pages>265-272</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><coden>JDSRET</coden><abstract>BACKGROUND:Several studies reported an association between immunodeficiency and non–AIDS-defining diseases. We investigated whether nonstructured treatment interruptions and episodes of viremia during suppressive combination antiretroviral therapy were independently associated with non-AIDS diseases.
METHODS:Six thousand four hundred forty patients with viral suppression (<50 copies/mL) within 48 weeks of starting combination antiretroviral therapy were selected from the Dutch ATHENA cohort. In proportional hazards models, associations between treatment interruptions, viral suppression, low-level (50–400 copies/mL), and high-level viremia (>400), and serious non-AIDS diseases (cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis) were investigated by including time-updated cumulative exposure to either viremia and interruptions or HIV RNA >400 copies per milliliter.
RESULTS:During 24,603 person-years, of which 88.5% occurred during viral suppression, 102 patients developed cardiovascular disease, 54 chronic renal failure, and 70 liver fibrosis/cirrhosis. Overall incidence of non-AIDS diseases ranged from 1.41 (95% confidence interval0.73 to 2.46) per 100 person-years for CD4 counts <200 to 0.71 (0.49 to 1.00) for CD4 ≥500 cells per cubic millimeter. Compared with viral suppression, high-level viremia was associated only with cardiovascular disease (relative hazard1.37, 1.04 to 1.81 per year longer), whereas interruptions and low-level viremia were not associated with non-AIDS diseases. Relative hazards for cumulative exposure to RNA >400 versus ≤400 copies per milliliter were 1.32 (1.01 to 1.73) for cardiovascular disease, 1.13 (0.66 to 1.92) for renal failure, and 0.86 (0.51 to 1.44) for fibrosis/cirrhosis.
CONCLUSIONS:Lower CD4 counts are associated with increased risk of non-AIDS diseases, whereas high-level viremia seems to be independently associated with cardiovascular disease. However, the power to detect associations with viremia or interruptions may have been limited as most events occurred during viral suppression.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>22531756</pmid><doi>10.1097/QAI.0b013e318258c651</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of acquired immune deficiency syndromes (1999), 2012-07, Vol.60 (3), p.265-272 |
| issn | 1525-4135 1944-7884 |
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| source | Ovid Lippincott Williams and Wilkins Journal Legacy Archive; MEDLINE; Journals@Ovid Complete; Free E- Journals |
| subjects | Adult AIDS/HIV Anti-HIV Agents - administration & dosage Anti-HIV Agents - therapeutic use Antiretroviral drugs Biological and medical sciences Cardiovascular disease Cardiovascular Diseases - etiology CD4 Lymphocyte Count Cohort Studies Female Fundamental and applied biological sciences. Psychology Glycoproteins HIV HIV Infections - complications HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology HIV-1 Human immunodeficiency virus Human viral diseases Humans Infectious diseases Liver Cirrhosis - etiology Male Medical sciences Microbiology Middle Aged Miscellaneous Netherlands Proportional Hazards Models Renal Insufficiency, Chronic - etiology Risk Factors RNA, Viral - blood Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral infections Viremia - drug therapy Viremia - immunology Viremia - virology Virology |
| title | Episodes of HIV Viremia and the Risk of Non-AIDS Diseases in Patients on Suppressive Antiretroviral Therapy |
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