Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy
The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational stud...
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| Veröffentlicht in: | AIDS (London) 2008-07, Vol.22 (12), p.1417-1423 |
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| creator | PEUCHANT, Olivia THIEBAUT, Rodolphe CAPDEPONT, Sophie LAVIGNOLLE-AURILLAC, Valérie NEAU, Didier MORLAT, Philippe DABIS, Francois FLEURY, Hervé MASQUELIER, Bernard |
| description | The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients.
We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model.
Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count.
The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation. |
| doi_str_mv | 10.1097/qad.0b013e3283034953 |
| format | Article |
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We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model.
Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count.
The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/qad.0b013e3283034953</identifier><identifier>PMID: 18614864</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>AIDS/HIV ; Anti-HIV Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; CD4 Lymphocyte Count ; Drug Resistance, Viral - genetics ; Female ; Genotype ; HIV Infections - drug therapy ; HIV Infections - transmission ; HIV Infections - virology ; HIV Protease - genetics ; HIV Reverse Transcriptase - genetics ; HIV-1 - drug effects ; HIV-1 - genetics ; HIV-1 - isolation & purification ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Male ; Medical sciences ; Mutation ; Pharmacology. Drug treatments ; Polymerase Chain Reaction - methods ; Retrospective Studies ; RNA, Viral - blood ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral Load</subject><ispartof>AIDS (London), 2008-07, Vol.22 (12), p.1417-1423</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-4d452523e3d147db15823aeaed8159d1070ebf26d6d2ed5bf7cadfe82df50c653</citedby><cites>FETCH-LOGICAL-c478t-4d452523e3d147db15823aeaed8159d1070ebf26d6d2ed5bf7cadfe82df50c653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20550994$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18614864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PEUCHANT, Olivia</creatorcontrib><creatorcontrib>THIEBAUT, Rodolphe</creatorcontrib><creatorcontrib>CAPDEPONT, Sophie</creatorcontrib><creatorcontrib>LAVIGNOLLE-AURILLAC, Valérie</creatorcontrib><creatorcontrib>NEAU, Didier</creatorcontrib><creatorcontrib>MORLAT, Philippe</creatorcontrib><creatorcontrib>DABIS, Francois</creatorcontrib><creatorcontrib>FLEURY, Hervé</creatorcontrib><creatorcontrib>MASQUELIER, Bernard</creatorcontrib><creatorcontrib>ANRS CO3 Aquitaine Cohort</creatorcontrib><title>Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients.
We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model.
Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count.
The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.</description><subject>AIDS/HIV</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>CD4 Lymphocyte Count</subject><subject>Drug Resistance, Viral - genetics</subject><subject>Female</subject><subject>Genotype</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - transmission</subject><subject>HIV Infections - virology</subject><subject>HIV Protease - genetics</subject><subject>HIV Reverse Transcriptase - genetics</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - isolation & purification</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Retrospective Studies</subject><subject>RNA, Viral - blood</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral Load</subject><issn>0269-9370</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1LHEEQxRsxxI3mPwjSF3Mbrf6a6TmK-VAQQkC9Dj3T1dgyO7129Qr739vikkAuOT2o-tWDV4-xLwLOBfTdxbPz5zCCUKikVaB0b9QBWwndqcaYThyyFci2b3rVwRH7RPQEAAas_ciOhG2Ftq1esekuu4XWkSimhafAr28eGsHXcUk5ll2TkSIVtxT-4nKsStwtntfxJi2EvCQeYqbSzHHBuioxY8npJWY38_KI2W12J-xDcDPh570es_sf3--urpvbXz9vri5vm0l3tjTaayONrHl8DeFHYaxUDh16K0zvBXSAY5Ctb71Eb8bQTc4HtNIHA1Nr1DH7-u67yel5i1SGmmvCeXYLpi0Nba-gM0r-F5QCVH2sqqB-B6eciDKGYZPj2uXdIGB4a2H4fflt-LeFena699-Oa_R_j_Zvr8DZHnA0uTnUDqZIfzgJxkDfa_UK10GSgQ</recordid><startdate>20080731</startdate><enddate>20080731</enddate><creator>PEUCHANT, Olivia</creator><creator>THIEBAUT, Rodolphe</creator><creator>CAPDEPONT, Sophie</creator><creator>LAVIGNOLLE-AURILLAC, Valérie</creator><creator>NEAU, Didier</creator><creator>MORLAT, Philippe</creator><creator>DABIS, Francois</creator><creator>FLEURY, Hervé</creator><creator>MASQUELIER, Bernard</creator><general>Lippincott Williams & Wilkins</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>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20080731</creationdate><title>Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy</title><author>PEUCHANT, Olivia ; THIEBAUT, Rodolphe ; CAPDEPONT, Sophie ; LAVIGNOLLE-AURILLAC, Valérie ; NEAU, Didier ; MORLAT, Philippe ; DABIS, Francois ; FLEURY, Hervé ; MASQUELIER, Bernard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-4d452523e3d147db15823aeaed8159d1070ebf26d6d2ed5bf7cadfe82df50c653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>AIDS/HIV</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>CD4 Lymphocyte Count</topic><topic>Drug Resistance, Viral - genetics</topic><topic>Female</topic><topic>Genotype</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - transmission</topic><topic>HIV Infections - virology</topic><topic>HIV Protease - genetics</topic><topic>HIV Reverse Transcriptase - genetics</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - isolation & purification</topic><topic>Human immunodeficiency virus 1</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Retrospective Studies</topic><topic>RNA, Viral - blood</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PEUCHANT, Olivia</creatorcontrib><creatorcontrib>THIEBAUT, Rodolphe</creatorcontrib><creatorcontrib>CAPDEPONT, Sophie</creatorcontrib><creatorcontrib>LAVIGNOLLE-AURILLAC, Valérie</creatorcontrib><creatorcontrib>NEAU, Didier</creatorcontrib><creatorcontrib>MORLAT, Philippe</creatorcontrib><creatorcontrib>DABIS, Francois</creatorcontrib><creatorcontrib>FLEURY, Hervé</creatorcontrib><creatorcontrib>MASQUELIER, Bernard</creatorcontrib><creatorcontrib>ANRS CO3 Aquitaine Cohort</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>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PEUCHANT, Olivia</au><au>THIEBAUT, Rodolphe</au><au>CAPDEPONT, Sophie</au><au>LAVIGNOLLE-AURILLAC, Valérie</au><au>NEAU, Didier</au><au>MORLAT, Philippe</au><au>DABIS, Francois</au><au>FLEURY, Hervé</au><au>MASQUELIER, Bernard</au><aucorp>ANRS CO3 Aquitaine Cohort</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2008-07-31</date><risdate>2008</risdate><volume>22</volume><issue>12</issue><spage>1417</spage><epage>1423</epage><pages>1417-1423</pages><issn>0269-9370</issn><eissn>1473-5571</eissn><abstract>The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients.
We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model.
Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count.
The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>18614864</pmid><doi>10.1097/qad.0b013e3283034953</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | AIDS (London), 2008-07, Vol.22 (12), p.1417-1423 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | AIDS/HIV Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences CD4 Lymphocyte Count Drug Resistance, Viral - genetics Female Genotype HIV Infections - drug therapy HIV Infections - transmission HIV Infections - virology HIV Protease - genetics HIV Reverse Transcriptase - genetics HIV-1 - drug effects HIV-1 - genetics HIV-1 - isolation & purification Human immunodeficiency virus 1 Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Male Medical sciences Mutation Pharmacology. Drug treatments Polymerase Chain Reaction - methods Retrospective Studies RNA, Viral - blood Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load |
| title | Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy |
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