HIV-1 sensitivity to zidovudine and clinical outcome in children
In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and cli...
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| Veröffentlicht in: | The Lancet (British edition) 1992-01, Vol.339 (8784), p.15-19 |
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| creator | Tudor-Williams, G. McKinney, R.E. Walter, E. Santacroce, S. O'Donnell, K. Wilfert, C.M. Rudoll, T. Tudor-Williams, G. St Clair, M.H. Maha, M. Vavro, C.L. Mintz, M. Connor, E.M. |
| description | In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and clinical outcome in children, in whom disease progression is more rapid than in adults. We studied 23 children with symptoms of HIV-1 disease during extended monotherapy with zidovudine. An in-vitro assay was used to determine the concentration of zidovudine required to inhibit by 50% the replication of viral isolates (IC
50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p |
| doi_str_mv | 10.1016/0140-6736(92)90140-X |
| format | Article |
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50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p<0·001) but no relation between IC
50 and age at start of therapy or length of time on treatment. Age-adjusted CD4 lymphocyte counts were lower at the start of treatment (p=0·02) and at the time of sampling (p=0·01) in children whose viral isolates had an increased zidovudine IC
50. Initial serum p24 antigen levels were not predictive of subsequent emergence of resistant virus, but at the time of sampling for viral sensitivity higher p24 antigen levels were associated with raised IC
50 (p=0·004). The findings suggest that most children who become unresponsive to monotherapy with zidovudine, as judged by clinical criteria, will have changes in in-vitro sensitivity to the drug. In these children, an alternative antiretroviral therapy should be considered.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/0140-6736(92)90140-X</identifier><identifier>PMID: 1345951</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Acquired immune deficiency syndrome ; Acquired Immunodeficiency Syndrome - drug therapy ; Acquired Immunodeficiency Syndrome - immunology ; Acquired Immunodeficiency Syndrome - mortality ; AIDS ; AIDS/HIV ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiretroviral agents ; Antiviral agents ; Biological and medical sciences ; CD4-Positive T-Lymphocytes ; Child ; Child, Preschool ; Children & youth ; Clinical outcomes ; Drug Resistance, Microbial ; Drugs ; Follow-Up Studies ; Health care ; HIV Core Protein p24 - analysis ; HIV-1 - drug effects ; HIV-1 - immunology ; Humans ; In Vitro Techniques ; Infant ; Leukocyte Count - drug effects ; Lymphocytes ; Medical research ; Medical sciences ; Pharmacology. Drug treatments ; Time Factors ; Treatment Outcome ; Virus Replication - drug effects ; Zidovudine - administration & dosage</subject><ispartof>The Lancet (British edition), 1992-01, Vol.339 (8784), p.15-19</ispartof><rights>1992</rights><rights>1992 INIST-CNRS</rights><rights>Copyright Lancet Ltd. Jan 4, 1992</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-ebeaabbab8ea3fbfe5cae57a77dd2e0d7ca501211a40b9659436a2a336942f4b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/198994470?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5149003$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1345951$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tudor-Williams, G.</creatorcontrib><creatorcontrib>McKinney, R.E.</creatorcontrib><creatorcontrib>Walter, E.</creatorcontrib><creatorcontrib>Santacroce, S.</creatorcontrib><creatorcontrib>O'Donnell, K.</creatorcontrib><creatorcontrib>Wilfert, C.M.</creatorcontrib><creatorcontrib>Rudoll, T.</creatorcontrib><creatorcontrib>Tudor-Williams, G.</creatorcontrib><creatorcontrib>St Clair, M.H.</creatorcontrib><creatorcontrib>Maha, M.</creatorcontrib><creatorcontrib>Vavro, C.L.</creatorcontrib><creatorcontrib>Mintz, M.</creatorcontrib><creatorcontrib>Connor, E.M.</creatorcontrib><title>HIV-1 sensitivity to zidovudine and clinical outcome in children</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and clinical outcome in children, in whom disease progression is more rapid than in adults. We studied 23 children with symptoms of HIV-1 disease during extended monotherapy with zidovudine. An in-vitro assay was used to determine the concentration of zidovudine required to inhibit by 50% the replication of viral isolates (IC
50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p<0·001) but no relation between IC
50 and age at start of therapy or length of time on treatment. Age-adjusted CD4 lymphocyte counts were lower at the start of treatment (p=0·02) and at the time of sampling (p=0·01) in children whose viral isolates had an increased zidovudine IC
50. Initial serum p24 antigen levels were not predictive of subsequent emergence of resistant virus, but at the time of sampling for viral sensitivity higher p24 antigen levels were associated with raised IC
50 (p=0·004). The findings suggest that most children who become unresponsive to monotherapy with zidovudine, as judged by clinical criteria, will have changes in in-vitro sensitivity to the drug. In these children, an alternative antiretroviral therapy should be considered.</description><subject>Acquired immune deficiency syndrome</subject><subject>Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>Acquired Immunodeficiency Syndrome - immunology</subject><subject>Acquired Immunodeficiency Syndrome - mortality</subject><subject>AIDS</subject><subject>AIDS/HIV</subject><subject>Antibiotics. Antiinfectious agents. 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Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tudor-Williams, G.</au><au>McKinney, R.E.</au><au>Walter, E.</au><au>Santacroce, S.</au><au>O'Donnell, K.</au><au>Wilfert, C.M.</au><au>Rudoll, T.</au><au>Tudor-Williams, G.</au><au>St Clair, M.H.</au><au>Maha, M.</au><au>Vavro, C.L.</au><au>Mintz, M.</au><au>Connor, E.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HIV-1 sensitivity to zidovudine and clinical outcome in children</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>1992-01-04</date><risdate>1992</risdate><volume>339</volume><issue>8784</issue><spage>15</spage><epage>19</epage><pages>15-19</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and clinical outcome in children, in whom disease progression is more rapid than in adults. We studied 23 children with symptoms of HIV-1 disease during extended monotherapy with zidovudine. An in-vitro assay was used to determine the concentration of zidovudine required to inhibit by 50% the replication of viral isolates (IC
50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p<0·001) but no relation between IC
50 and age at start of therapy or length of time on treatment. Age-adjusted CD4 lymphocyte counts were lower at the start of treatment (p=0·02) and at the time of sampling (p=0·01) in children whose viral isolates had an increased zidovudine IC
50. Initial serum p24 antigen levels were not predictive of subsequent emergence of resistant virus, but at the time of sampling for viral sensitivity higher p24 antigen levels were associated with raised IC
50 (p=0·004). The findings suggest that most children who become unresponsive to monotherapy with zidovudine, as judged by clinical criteria, will have changes in in-vitro sensitivity to the drug. In these children, an alternative antiretroviral therapy should be considered.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>1345951</pmid><doi>10.1016/0140-6736(92)90140-X</doi><tpages>5</tpages></addata></record> |
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| ispartof | The Lancet (British edition), 1992-01, Vol.339 (8784), p.15-19 |
| issn | 0140-6736 1474-547X |
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| subjects | Acquired immune deficiency syndrome Acquired Immunodeficiency Syndrome - drug therapy Acquired Immunodeficiency Syndrome - immunology Acquired Immunodeficiency Syndrome - mortality AIDS AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral agents Antiviral agents Biological and medical sciences CD4-Positive T-Lymphocytes Child Child, Preschool Children & youth Clinical outcomes Drug Resistance, Microbial Drugs Follow-Up Studies Health care HIV Core Protein p24 - analysis HIV-1 - drug effects HIV-1 - immunology Humans In Vitro Techniques Infant Leukocyte Count - drug effects Lymphocytes Medical research Medical sciences Pharmacology. Drug treatments Time Factors Treatment Outcome Virus Replication - drug effects Zidovudine - administration & dosage |
| title | HIV-1 sensitivity to zidovudine and clinical outcome in children |
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