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Selection of Zidovudine Resistance Mutations and Escape of Human Immunodeficiency Virus Type 1 from Antiretroviral Pressure in Stavudine-Treated Pediatric Patients
The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reduction...
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| Published in: | The Journal of infectious diseases 2002-04, Vol.185 (8), p.1070-1076 |
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| container_end_page | 1076 |
| container_issue | 8 |
| container_start_page | 1070 |
| container_title | The Journal of infectious diseases |
| container_volume | 185 |
| creator | Maxeiner, Horst-Guenter Keulen, Wilco Schuurman, Rob Bijen, Marc Graaf, Loek de van Wijk, Albert Back, Nicole Kline, Mark W. Boucher, Charles A. B. Nijhuis, Monique |
| description | The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reductions in virus load, and all others had no detectable virologic response. In both the responders and nonresponders, no changes in stavudine susceptibility or specific baseline/emergent mutations in reverse transcriptase were observed. Only posttherapy HIV isolates from transient responders had elevated IC50 values for stavudine. In 2 of the 3 transient responders, substitutions at codons 41, 210, and 215 were selected. The significance of these mutations was confirmed in viral competition experiments, site-directed mutagenesis, and in vitro selection. Selection of mutations previously associated with zidovudine resistance can be an important mechanism through which HIV may escape stavudine. The effect of these mutations on phenotypic stavudine susceptibility is relatively small but apparently large enough to be clinically significant. |
| doi_str_mv | 10.1086/339817 |
| format | article |
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The significance of these mutations was confirmed in viral competition experiments, site-directed mutagenesis, and in vitro selection. Selection of mutations previously associated with zidovudine resistance can be an important mechanism through which HIV may escape stavudine. The effect of these mutations on phenotypic stavudine susceptibility is relatively small but apparently large enough to be clinically significant.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/339817</identifier><identifier>PMID: 11930317</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: University of Chicago Press</publisher><subject>Acquired Immunodeficiency Syndrome - drug therapy ; Acquired Immunodeficiency Syndrome - virology ; Anti-HIV Agents - therapeutic use ; Antiretrovirals ; Antivirals ; Biological and medical sciences ; Child ; Child, Preschool ; Drug Resistance, Viral ; Genetic mutation ; HIV ; HIV 1 ; HIV Reverse Transcriptase - genetics ; HIV-1 - drug effects ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Infant ; Infectious diseases ; Inhibitory concentration 50 ; Major Articles ; Medical sciences ; Mutagenesis, Site-Directed ; Mutation ; RNA ; RNA, Viral - blood ; Stavudine - therapeutic use ; Transponders ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. 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B.</creatorcontrib><creatorcontrib>Nijhuis, Monique</creatorcontrib><title>Selection of Zidovudine Resistance Mutations and Escape of Human Immunodeficiency Virus Type 1 from Antiretroviral Pressure in Stavudine-Treated Pediatric Patients</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reductions in virus load, and all others had no detectable virologic response. In both the responders and nonresponders, no changes in stavudine susceptibility or specific baseline/emergent mutations in reverse transcriptase were observed. Only posttherapy HIV isolates from transient responders had elevated IC50 values for stavudine. In 2 of the 3 transient responders, substitutions at codons 41, 210, and 215 were selected. The significance of these mutations was confirmed in viral competition experiments, site-directed mutagenesis, and in vitro selection. Selection of mutations previously associated with zidovudine resistance can be an important mechanism through which HIV may escape stavudine. The effect of these mutations on phenotypic stavudine susceptibility is relatively small but apparently large enough to be clinically significant.</description><subject>Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>Acquired Immunodeficiency Syndrome - virology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretrovirals</subject><subject>Antivirals</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Drug Resistance, Viral</subject><subject>Genetic mutation</subject><subject>HIV</subject><subject>HIV 1</subject><subject>HIV Reverse Transcriptase - genetics</subject><subject>HIV-1 - drug effects</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infant</subject><subject>Infectious diseases</subject><subject>Inhibitory concentration 50</subject><subject>Major Articles</subject><subject>Medical sciences</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>RNA</subject><subject>RNA, Viral - blood</subject><subject>Stavudine - therapeutic use</subject><subject>Transponders</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral Load</subject><subject>Virology</subject><subject>Viruses</subject><subject>Zidovudine - therapeutic use</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNp10V2L1DAUBuAiiruu-g-UKOhdNR9t0l4uw-osrjo4RWRvSiY5hYxtMuZjcX6Pf9QMHXZA8CqQ8_CekLconhP8juCGv2esbYh4UJyTmomSc8IeFucYU1qSpm3PiichbDHGFePicXFGSMswI-K8-LOGEVQ0ziI3oFuj3V3SxgL6BsGEKK0C9DlFeRABSavRVVByBwe9TJO06HqaknUaBqMMWLVH341PAXX7jAgavJvQpY3GQ_Tuzng5opWHEJIHZCxaRzkvLDsPMoJGK9BGRm8UWuWtYGN4Wjwa5Bjg2fG8KLoPV91iWd58_Xi9uLwpVdWQWLZaaN5gwQelmaYbRiWnUjEOoh5UzTc83zcSiNBCblrFoaXDhlSVAt7UA7so3s6xO-9-JQixn0xQMI7SgkuhJw2jbUVFhq__gVuXvM1P6yllLaZNLU5pyrsQPAz9zptJ-n1PcH-orJ8ry_DlMS1tJtAnduwogzdHIPPXj4PPpZhwcozTijUH92p2Lu3-v-zFbLYhOn-vGCZMCMHzvJznuXv4fT-X_mfPBRN1v_xx239qF8tuzb_0HfsL1fTDcQ</recordid><startdate>20020415</startdate><enddate>20020415</enddate><creator>Maxeiner, Horst-Guenter</creator><creator>Keulen, Wilco</creator><creator>Schuurman, Rob</creator><creator>Bijen, Marc</creator><creator>Graaf, Loek de</creator><creator>van Wijk, Albert</creator><creator>Back, Nicole</creator><creator>Kline, Mark W.</creator><creator>Boucher, Charles A. 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B.</au><au>Nijhuis, Monique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selection of Zidovudine Resistance Mutations and Escape of Human Immunodeficiency Virus Type 1 from Antiretroviral Pressure in Stavudine-Treated Pediatric Patients</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>The Journal of Infectious Diseases</stitle><addtitle>The Journal of Infectious Diseases</addtitle><date>2002-04-15</date><risdate>2002</risdate><volume>185</volume><issue>8</issue><spage>1070</spage><epage>1076</epage><pages>1070-1076</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reductions in virus load, and all others had no detectable virologic response. In both the responders and nonresponders, no changes in stavudine susceptibility or specific baseline/emergent mutations in reverse transcriptase were observed. Only posttherapy HIV isolates from transient responders had elevated IC50 values for stavudine. In 2 of the 3 transient responders, substitutions at codons 41, 210, and 215 were selected. The significance of these mutations was confirmed in viral competition experiments, site-directed mutagenesis, and in vitro selection. Selection of mutations previously associated with zidovudine resistance can be an important mechanism through which HIV may escape stavudine. The effect of these mutations on phenotypic stavudine susceptibility is relatively small but apparently large enough to be clinically significant.</abstract><cop>Chicago, IL</cop><pub>University of Chicago Press</pub><pmid>11930317</pmid><doi>10.1086/339817</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of infectious diseases, 2002-04, Vol.185 (8), p.1070-1076 |
| issn | 0022-1899 1537-6613 |
| language | eng |
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| source | JSTOR Archival Journals and Primary Sources Collection【Remote access available】; Oxford Journals Online |
| subjects | Acquired Immunodeficiency Syndrome - drug therapy Acquired Immunodeficiency Syndrome - virology Anti-HIV Agents - therapeutic use Antiretrovirals Antivirals Biological and medical sciences Child Child, Preschool Drug Resistance, Viral Genetic mutation HIV HIV 1 HIV Reverse Transcriptase - genetics HIV-1 - drug effects Human immunodeficiency virus 1 Human viral diseases Humans Infant Infectious diseases Inhibitory concentration 50 Major Articles Medical sciences Mutagenesis, Site-Directed Mutation RNA RNA, Viral - blood Stavudine - therapeutic use Transponders Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load Virology Viruses Zidovudine - therapeutic use |
| title | Selection of Zidovudine Resistance Mutations and Escape of Human Immunodeficiency Virus Type 1 from Antiretroviral Pressure in Stavudine-Treated Pediatric Patients |
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