| Low-frequency nevirapine resistance at multiple sites may predict treatment failure in infants on nevirapine-based treatment. | |
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MedLine Citation:
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PMID: 22395670 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Resistance commonly arises in infants exposed to single-dose nevirapine (sdNVP) for prevention of mother to child transmission. Although K103N and Y181C are common following sdNVP, multiple other mutations also confer NVP resistance. It remains unclear whether specific NVP resistance mutations or combinations of mutations predict virologic failure in infants when present at low frequencies before NVP-based treatment. METHODS: Twenty sdNVP-exposed infants who were subsequently treated with NVP-based highly active antiretroviral therapy were examined. Pretreatment plasma samples were tested for the presence of NVP resistance mutations by allele-specific polymerase chain reaction for K103N and Y181C and ultradeep pyrosequencing (UDPS) for all primary NVP mutations. Viral levels were determined every 3 months for up to 24 months on NVP-highly active antiretroviral therapy. Cox proportional hazard models were used to determine correlates of viral failure. RESULTS: The NVP resistance mutations K103N or Y181C were detected in pretreatment plasma samples in 6 infants by allele-specific polymerase chain reaction. NVP resistance at these or other sites was detectable by UDPS in 10 of 20 infants tested. Virologic failure occurred in 50% of infants with any NVP resistance mutations detected, whereas only 20% of infants without resistance experienced viral failure, but the difference was not significant (P = 0.19). An increase in the number of NVP resistance mutations detectable by UDPS in an infant was significantly associated with an increased risk of virologic failure [HR = 1.79 (95% confidence interval: 1.07 to 2.99), P = 0.027]. CONCLUSIONS: Low frequencies of multiple NVP resistance mutations, in addition to K103N and Y181C, present in infants before NVP-based treatment may predict treatment outcome. |
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Authors:
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Dara A Lehman; Dalton C Wamalwa; Connor O McCoy; Frederick A Matsen; Agnes Langat; Bhavna H Chohan; Sarah Benki-Nugent; Rebecca Custers-Allen; Frederic D Bushman; Grace C John-Stewart; Julie Overbaugh |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of acquired immune deficiency syndromes (1999) Volume: 60 ISSN: 1944-7884 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-26 Completed Date: 2012-09-06 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: United States |
Other Details:
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Languages: eng Pagination: 225-33 Citation Subset: IM; X |
Affiliation:
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Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Anti-HIV Agents / administration & dosage*, adverse effects Antiretroviral Therapy, Highly Active Child, Preschool Drug Resistance, Viral / genetics Female HIV Infections / drug therapy, prevention & control*, transmission, virology HIV Reverse Transcriptase / genetics HIV-1 / drug effects, enzymology, genetics Humans Infant Infectious Disease Transmission, Vertical / prevention & control* Kenya Mutation Nevirapine / administration & dosage*, adverse effects Pregnancy Treatment Failure |
| Grant Support | |
ID/Acronym/Agency:
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AI076105/AI/NIAID NIH HHS; HD23412/HD/NICHD NIH HHS; P30 AI027757/AI/NIAID NIH HHS; P30 AI027757/AI/NIAID NIH HHS; R01 AI076105-04/AI/NIAID NIH HHS; R01 HD023412/HD/NICHD NIH HHS; R01 HD023412-18/HD/NICHD NIH HHS; R01 HD023412-19/HD/NICHD NIH HHS; R01 HD023412-20/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 129618-40-2/Nevirapine; EC 2.7.7.-/reverse transcriptase, Human immunodeficiency virus 1; EC 2.7.7.49/HIV Reverse Transcriptase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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