Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy
Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being e...
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| Veröffentlicht in: | PloS one 2011-06, Vol.6 (6), p.e21081-e21081 |
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| creator | Zhu, Weijun Jiao, Yanmei Lei, Rongyue Hua, Wei Wang, Rui Ji, Yunxia Liu, Zhiying Wei, Feili Zhang, Tong Shi, Xuanlin Wu, Hao Zhang, Linqi |
| description | Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment.
In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period.
Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART. |
| doi_str_mv | 10.1371/journal.pone.0021081 |
| format | Article |
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In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period.
Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0021081</identifier><identifier>PMID: 21687638</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adult ; AIDS ; Analysis ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral Therapy, Highly Active ; Bacteriophage M13 - genetics ; Base Sequence ; Biology ; Biomarkers ; CD4 antigen ; CD4-Positive T-Lymphocytes - metabolism ; Dementia ; Deoxyribonucleic acid ; DNA ; DNA Primers - genetics ; DNA, Viral - genetics ; DNA, Viral - metabolism ; Drug therapy ; Eradication ; Female ; Genetic research ; Half-Life ; Highly active antiretroviral therapy ; HIV ; HIV Long Terminal Repeat - genetics ; HIV-1 - drug effects ; HIV-1 - genetics ; HIV-1 - physiology ; Hospitals ; Human immunodeficiency virus ; Humans ; Immunological memory ; Infections ; Infectious diseases ; Integrase ; Intervals ; Lipopolysaccharides ; Load distribution ; Lymphocytes ; Lymphocytes T ; Male ; Medical treatment ; Medicine ; Memory cells ; Middle Aged ; Mitogens ; Oligonucleotide Probes - genetics ; Pathogens ; Patients ; Peripheral blood ; Public health ; Receptors, CCR5 - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; T cells ; Therapy ; Time Factors ; Viral Load - drug effects ; Virus Latency - drug effects ; Virus Replication - drug effects ; Young Adult</subject><ispartof>PloS one, 2011-06, Vol.6 (6), p.e21081-e21081</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Zhu et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-809e6a53a31ed70d5d0a57b84114a63fc03253b852b4cc7988f9ad94494764673</citedby><cites>FETCH-LOGICAL-c691t-809e6a53a31ed70d5d0a57b84114a63fc03253b852b4cc7988f9ad94494764673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110824/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110824/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21687638$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jiang, Shibo</contributor><creatorcontrib>Zhu, Weijun</creatorcontrib><creatorcontrib>Jiao, Yanmei</creatorcontrib><creatorcontrib>Lei, Rongyue</creatorcontrib><creatorcontrib>Hua, Wei</creatorcontrib><creatorcontrib>Wang, Rui</creatorcontrib><creatorcontrib>Ji, Yunxia</creatorcontrib><creatorcontrib>Liu, Zhiying</creatorcontrib><creatorcontrib>Wei, Feili</creatorcontrib><creatorcontrib>Zhang, Tong</creatorcontrib><creatorcontrib>Shi, Xuanlin</creatorcontrib><creatorcontrib>Wu, Hao</creatorcontrib><creatorcontrib>Zhang, Linqi</creatorcontrib><title>Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment.
In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period.
Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adult</subject><subject>AIDS</subject><subject>Analysis</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Bacteriophage M13 - genetics</subject><subject>Base Sequence</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Dementia</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Primers - genetics</subject><subject>DNA, Viral - genetics</subject><subject>DNA, Viral - metabolism</subject><subject>Drug therapy</subject><subject>Eradication</subject><subject>Female</subject><subject>Genetic research</subject><subject>Half-Life</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV Long Terminal Repeat - genetics</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - physiology</subject><subject>Hospitals</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunological memory</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Integrase</subject><subject>Intervals</subject><subject>Lipopolysaccharides</subject><subject>Load distribution</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Memory cells</subject><subject>Middle Aged</subject><subject>Mitogens</subject><subject>Oligonucleotide Probes - genetics</subject><subject>Pathogens</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Public health</subject><subject>Receptors, CCR5 - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sequence Analysis, DNA</subject><subject>T cells</subject><subject>Therapy</subject><subject>Time Factors</subject><subject>Viral Load - 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genetics</topic><topic>Base Sequence</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Dementia</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Primers - genetics</topic><topic>DNA, Viral - genetics</topic><topic>DNA, Viral - metabolism</topic><topic>Drug therapy</topic><topic>Eradication</topic><topic>Female</topic><topic>Genetic research</topic><topic>Half-Life</topic><topic>Highly active antiretroviral therapy</topic><topic>HIV</topic><topic>HIV Long Terminal Repeat - genetics</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - physiology</topic><topic>Hospitals</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunological memory</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Integrase</topic><topic>Intervals</topic><topic>Lipopolysaccharides</topic><topic>Load distribution</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Medicine</topic><topic>Memory cells</topic><topic>Middle Aged</topic><topic>Mitogens</topic><topic>Oligonucleotide Probes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Weijun</au><au>Jiao, Yanmei</au><au>Lei, Rongyue</au><au>Hua, Wei</au><au>Wang, Rui</au><au>Ji, Yunxia</au><au>Liu, Zhiying</au><au>Wei, Feili</au><au>Zhang, Tong</au><au>Shi, Xuanlin</au><au>Wu, Hao</au><au>Zhang, Linqi</au><au>Jiang, Shibo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-06-08</date><risdate>2011</risdate><volume>6</volume><issue>6</issue><spage>e21081</spage><epage>e21081</epage><pages>e21081-e21081</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment.
In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period.
Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21687638</pmid><doi>10.1371/journal.pone.0021081</doi><tpages>e21081</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-06, Vol.6 (6), p.e21081-e21081 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1304903587 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acquired immune deficiency syndrome Adult AIDS Analysis Antiretroviral agents Antiretroviral drugs Antiretroviral Therapy, Highly Active Bacteriophage M13 - genetics Base Sequence Biology Biomarkers CD4 antigen CD4-Positive T-Lymphocytes - metabolism Dementia Deoxyribonucleic acid DNA DNA Primers - genetics DNA, Viral - genetics DNA, Viral - metabolism Drug therapy Eradication Female Genetic research Half-Life Highly active antiretroviral therapy HIV HIV Long Terminal Repeat - genetics HIV-1 - drug effects HIV-1 - genetics HIV-1 - physiology Hospitals Human immunodeficiency virus Humans Immunological memory Infections Infectious diseases Integrase Intervals Lipopolysaccharides Load distribution Lymphocytes Lymphocytes T Male Medical treatment Medicine Memory cells Middle Aged Mitogens Oligonucleotide Probes - genetics Pathogens Patients Peripheral blood Public health Receptors, CCR5 - genetics Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA T cells Therapy Time Factors Viral Load - drug effects Virus Latency - drug effects Virus Replication - drug effects Young Adult |
| title | Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T03%3A46%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rapid%20turnover%20of%202-LTR%20HIV-1%20DNA%20during%20early%20stage%20of%20highly%20active%20antiretroviral%20therapy&rft.jtitle=PloS%20one&rft.au=Zhu,%20Weijun&rft.date=2011-06-08&rft.volume=6&rft.issue=6&rft.spage=e21081&rft.epage=e21081&rft.pages=e21081-e21081&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0021081&rft_dat=%3Cgale_plos_%3EA476888594%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1304903587&rft_id=info:pmid/21687638&rft_galeid=A476888594&rft_doaj_id=oai_doaj_org_article_4ce000e8fd6f495c872c72cad351b6a9&rfr_iscdi=true |