Document Detail


Low-frequency nevirapine resistance at multiple sites may predict treatment failure in infants on nevirapine-based treatment.
MedLine Citation:
PMID:  22395670     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
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:
Created Date:  2012-06-26     Completed Date:  2012-09-06     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  225-33     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
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:
AI076105/AI/NIAID NIH HHS; HD23412/HD/NICHD NIH HHS; K01 NS080637/NS/NINDS NIH HHS; P30 AI027757/AI/NIAID NIH HHS; P30 AI027757/AI/NIAID NIH HHS; P30 CA015704/CA/NCI NIH HHS; R01 AI076105/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:
0/Anti-HIV Agents; 99DK7FVK1H/Nevirapine; EC 2.7.7.-/reverse transcriptase, Human immunodeficiency virus 1; EC 2.7.7.49/HIV Reverse Transcriptase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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