Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment
BACKGROUND:The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatmen...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2020-12, Vol.85 (4), p.517-524 |
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| creator | Thorball, Christian W. Borghesi, Alessandro Bachmann, Nadine Von Siebenthal, Chantal Vongrad, Valentina Turk, Teja Neumann, Kathrin Beerenwinkel, Niko Bogojeska, Jasmina Roth, Volker Kok, Yik Lim Parbhoo, Sonali Wieser, Mario Böni, Jürg Perreau, Matthieu Klimkait, Thomas Yerly, Sabine Battegay, Manuel Rauch, Andri Schmid, Patrick Bernasconi, Enos Cavassini, Matthias Kouyos, Roger D. Günthard, Huldrych F. Metzner, Karin J. Fellay, Jacques |
| description | BACKGROUND:The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment (ART).
SETTING:Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study (SHCS), a nation-wide prospective observational study.
METHODS:We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size, at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readoutsthe reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.
RESULTS:Genome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART.
CONCLUSIONS:Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals. |
| doi_str_mv | 10.1097/QAI.0000000000002473 |
| format | Article |
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SETTING:Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study (SHCS), a nation-wide prospective observational study.
METHODS:We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size, at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readoutsthe reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.
RESULTS:Genome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART.
CONCLUSIONS:Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0000000000002473</identifier><identifier>PMID: 33136754</identifier><language>eng</language><publisher>United States: JAIDS Journal of Acquired Immune Deficiency Syndromes</publisher><subject>Anti-HIV Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Copy number ; Decay ; Decay rate ; Deoxyribonucleic acid ; DNA ; Eradication ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic variance ; Genetic Variation ; Genetics ; Genome, Human ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics - methods ; Genotype ; Genotyping ; HIV ; HIV Infections - drug therapy ; HIV Infections - genetics ; HIV-1 ; Human immunodeficiency virus ; Humans ; Leukocytes (mononuclear) ; Peripheral blood mononuclear cells ; Phenotypic variations ; Time Factors</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2020-12, Vol.85 (4), p.517-524</ispartof><rights>JAIDS Journal of Acquired Immune Deficiency Syndromes</rights><rights>Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4753-fecc8ce4306c2e9090e5dadaf4bbf2d5ce4974e82ff2395845b9a62bd623d0773</citedby><cites>FETCH-LOGICAL-c4753-fecc8ce4306c2e9090e5dadaf4bbf2d5ce4974e82ff2395845b9a62bd623d0773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf><![CDATA[$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&PDF=y&D=ovft&AN=00126334-202012010-00020$$EPDF$$P50$$Gwolterskluwer$$H]]></linktopdf><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00126334-202012010-00020$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>314,780,784,4609,27924,27925,64666,65461</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33136754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thorball, Christian W.</creatorcontrib><creatorcontrib>Borghesi, Alessandro</creatorcontrib><creatorcontrib>Bachmann, Nadine</creatorcontrib><creatorcontrib>Von Siebenthal, Chantal</creatorcontrib><creatorcontrib>Vongrad, Valentina</creatorcontrib><creatorcontrib>Turk, Teja</creatorcontrib><creatorcontrib>Neumann, Kathrin</creatorcontrib><creatorcontrib>Beerenwinkel, Niko</creatorcontrib><creatorcontrib>Bogojeska, Jasmina</creatorcontrib><creatorcontrib>Roth, Volker</creatorcontrib><creatorcontrib>Kok, Yik Lim</creatorcontrib><creatorcontrib>Parbhoo, Sonali</creatorcontrib><creatorcontrib>Wieser, Mario</creatorcontrib><creatorcontrib>Böni, Jürg</creatorcontrib><creatorcontrib>Perreau, Matthieu</creatorcontrib><creatorcontrib>Klimkait, Thomas</creatorcontrib><creatorcontrib>Yerly, Sabine</creatorcontrib><creatorcontrib>Battegay, Manuel</creatorcontrib><creatorcontrib>Rauch, Andri</creatorcontrib><creatorcontrib>Schmid, Patrick</creatorcontrib><creatorcontrib>Bernasconi, Enos</creatorcontrib><creatorcontrib>Cavassini, Matthias</creatorcontrib><creatorcontrib>Kouyos, Roger D.</creatorcontrib><creatorcontrib>Günthard, Huldrych F.</creatorcontrib><creatorcontrib>Metzner, Karin J.</creatorcontrib><creatorcontrib>Fellay, Jacques</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</creatorcontrib><creatorcontrib>the Swiss HIV Cohort Study</creatorcontrib><title>Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment (ART).
SETTING:Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study (SHCS), a nation-wide prospective observational study.
METHODS:We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size, at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readoutsthe reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.
RESULTS:Genome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART.
CONCLUSIONS:Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.</description><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Copy number</subject><subject>Decay</subject><subject>Decay rate</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Eradication</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variance</subject><subject>Genetic Variation</subject><subject>Genetics</subject><subject>Genome, Human</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics - methods</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - genetics</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Leukocytes (mononuclear)</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phenotypic variations</subject><subject>Time Factors</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERcuWf4CQJS5cUvwxjpPjqoXuSpVQP-BqOcmEdUnixXa2Kr8eV1sQ6oHOZUaa5301mpeQt5ydcFbrj5fL9Qn7pwRo-YIc8Rqg0FUFL_OshCqAS3VIXsd4yxgvAepX5FBKLkut4IhsVj4meo6TH10bqe9p2iBdrb8VnF5hxLDzLtBr9wupnTq6TpGeYWvv6ZVNSM_m4Kbv9HrebgPG6HZIl1NyAVPwOxfsQG8C2jTilI7JQW-HiG8e-4J8_fzp5nRVXHw5X58uL4oWtJJFj21btQiSla3AmtUMVWc720PT9KJTeVVrwEr0vZC1qkA1tS1F05VCdkxruSAf9r7b4H_OGJMZXWxxGOyEfo5GgNKSsSrzC_L-CXrr5zDl64xQTEPJKlFmCvZUG3yMAXuzDW604d5wZh6SMDkJ8zSJLHv3aD43I3Z_RX9en4FqD9z5IWGIP4b5DoPZoB3S5jlv-I80x5zPllAIJvLIOCsehEz-Bgpbo6s</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Thorball, Christian W.</creator><creator>Borghesi, Alessandro</creator><creator>Bachmann, Nadine</creator><creator>Von Siebenthal, Chantal</creator><creator>Vongrad, Valentina</creator><creator>Turk, Teja</creator><creator>Neumann, Kathrin</creator><creator>Beerenwinkel, Niko</creator><creator>Bogojeska, Jasmina</creator><creator>Roth, Volker</creator><creator>Kok, Yik Lim</creator><creator>Parbhoo, Sonali</creator><creator>Wieser, Mario</creator><creator>Böni, Jürg</creator><creator>Perreau, Matthieu</creator><creator>Klimkait, Thomas</creator><creator>Yerly, Sabine</creator><creator>Battegay, Manuel</creator><creator>Rauch, Andri</creator><creator>Schmid, Patrick</creator><creator>Bernasconi, Enos</creator><creator>Cavassini, Matthias</creator><creator>Kouyos, Roger D.</creator><creator>Günthard, Huldrych F.</creator><creator>Metzner, Karin J.</creator><creator>Fellay, Jacques</creator><general>JAIDS Journal of Acquired Immune Deficiency Syndromes</general><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>20201201</creationdate><title>Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment</title><author>Thorball, Christian W. ; Borghesi, Alessandro ; Bachmann, Nadine ; Von Siebenthal, Chantal ; Vongrad, Valentina ; Turk, Teja ; Neumann, Kathrin ; Beerenwinkel, Niko ; Bogojeska, Jasmina ; Roth, Volker ; Kok, Yik Lim ; Parbhoo, Sonali ; Wieser, Mario ; Böni, Jürg ; Perreau, Matthieu ; Klimkait, Thomas ; Yerly, Sabine ; Battegay, Manuel ; Rauch, Andri ; Schmid, Patrick ; Bernasconi, Enos ; Cavassini, Matthias ; Kouyos, Roger D. ; Günthard, Huldrych F. ; Metzner, Karin J. ; Fellay, Jacques</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4753-fecc8ce4306c2e9090e5dadaf4bbf2d5ce4974e82ff2395845b9a62bd623d0773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Copy number</topic><topic>Decay</topic><topic>Decay rate</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Eradication</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic variance</topic><topic>Genetic Variation</topic><topic>Genetics</topic><topic>Genome, Human</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genomics - methods</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - genetics</topic><topic>HIV-1</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Leukocytes (mononuclear)</topic><topic>Peripheral blood mononuclear cells</topic><topic>Phenotypic variations</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thorball, Christian W.</creatorcontrib><creatorcontrib>Borghesi, Alessandro</creatorcontrib><creatorcontrib>Bachmann, Nadine</creatorcontrib><creatorcontrib>Von Siebenthal, Chantal</creatorcontrib><creatorcontrib>Vongrad, Valentina</creatorcontrib><creatorcontrib>Turk, Teja</creatorcontrib><creatorcontrib>Neumann, Kathrin</creatorcontrib><creatorcontrib>Beerenwinkel, Niko</creatorcontrib><creatorcontrib>Bogojeska, Jasmina</creatorcontrib><creatorcontrib>Roth, Volker</creatorcontrib><creatorcontrib>Kok, Yik Lim</creatorcontrib><creatorcontrib>Parbhoo, Sonali</creatorcontrib><creatorcontrib>Wieser, Mario</creatorcontrib><creatorcontrib>Böni, Jürg</creatorcontrib><creatorcontrib>Perreau, Matthieu</creatorcontrib><creatorcontrib>Klimkait, Thomas</creatorcontrib><creatorcontrib>Yerly, Sabine</creatorcontrib><creatorcontrib>Battegay, Manuel</creatorcontrib><creatorcontrib>Rauch, Andri</creatorcontrib><creatorcontrib>Schmid, Patrick</creatorcontrib><creatorcontrib>Bernasconi, Enos</creatorcontrib><creatorcontrib>Cavassini, Matthias</creatorcontrib><creatorcontrib>Kouyos, Roger D.</creatorcontrib><creatorcontrib>Günthard, Huldrych F.</creatorcontrib><creatorcontrib>Metzner, Karin J.</creatorcontrib><creatorcontrib>Fellay, Jacques</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</creatorcontrib><creatorcontrib>the Swiss HIV Cohort Study</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>Thorball, Christian W.</au><au>Borghesi, Alessandro</au><au>Bachmann, Nadine</au><au>Von Siebenthal, Chantal</au><au>Vongrad, Valentina</au><au>Turk, Teja</au><au>Neumann, Kathrin</au><au>Beerenwinkel, Niko</au><au>Bogojeska, Jasmina</au><au>Roth, Volker</au><au>Kok, Yik Lim</au><au>Parbhoo, Sonali</au><au>Wieser, Mario</au><au>Böni, Jürg</au><au>Perreau, Matthieu</au><au>Klimkait, Thomas</au><au>Yerly, Sabine</au><au>Battegay, Manuel</au><au>Rauch, Andri</au><au>Schmid, Patrick</au><au>Bernasconi, Enos</au><au>Cavassini, Matthias</au><au>Kouyos, Roger D.</au><au>Günthard, Huldrych F.</au><au>Metzner, Karin J.</au><au>Fellay, Jacques</au><aucorp>Swiss HIV Cohort Study</aucorp><aucorp>the Swiss HIV Cohort Study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>85</volume><issue>4</issue><spage>517</spage><epage>524</epage><pages>517-524</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><abstract>BACKGROUND:The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment (ART).
SETTING:Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study (SHCS), a nation-wide prospective observational study.
METHODS:We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size, at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readoutsthe reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.
RESULTS:Genome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART.
CONCLUSIONS:Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.</abstract><cop>United States</cop><pub>JAIDS Journal of Acquired Immune Deficiency Syndromes</pub><pmid>33136754</pmid><doi>10.1097/QAI.0000000000002473</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Copy number Decay Decay rate Deoxyribonucleic acid DNA Eradication Genetic diversity Genetic Predisposition to Disease Genetic variance Genetic Variation Genetics Genome, Human Genome-wide association studies Genome-Wide Association Study Genomes Genomics - methods Genotype Genotyping HIV HIV Infections - drug therapy HIV Infections - genetics HIV-1 Human immunodeficiency virus Humans Leukocytes (mononuclear) Peripheral blood mononuclear cells Phenotypic variations Time Factors |
| title | Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment |
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