Document Detail


Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission.
MedLine Citation:
PMID:  21241214     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nevirapine resistance mutations arise commonly following single or extended-dose nevirapine (ED-NVP) prophylaxis to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), but decay within 6-12 months of single-dose exposure. Use of ED-NVP prophylaxis in infants is expected to rise, but data on decay of nevirapine resistance mutations in infants in whom ED-NVP failed remain limited. We assessed, in Ethiopian infants participating in the Six-Week Extended Nevirapine (SWEN) Trial, the prevalence and persistence of nevirapine resistance mutations at 6 and 12 months following single-dose or up to 6 weeks of ED-NVP, and correlated their presence with the timing of infection and the type of resistance mutations. Standard population genotyping followed by high-throughput cloning were done on dried blood spot samples collected during the trial. More infants who received ED-NVP had nevirapine resistance detected by standard population genotyping (high frequencies) at age 6 months compared with those who received single-dose nevirapine (SD-NVP) (58% of 24 vs. 26% of 19, respectively; p = 0.06). Moreover, 56% of ED-NVP-exposed infants with nevirapine resistance at age 6 months still had nevirapine resistance mutations present at high frequencies at age 1 year. Infants infected before 6 weeks of age who received either SD- or ED-NVP were more likely to have Y181C or K103N; these mutations were also more likely to persist at high frequencies through 1 year of age. HIV-infected infants in whom ED-NVP prophylaxis fails are likely to experience delayed clearance of nevirapine-resistant virus in the first year of life, which in turn places them at risk for early selection of multidrug-resistant HIV after initial therapy with nonnucleoside reverse transcriptase inhibitor-based regimens.
Authors:
Deborah Persaud; Abubaker Bedri; Carrie Ziemniak; Anitha Moorthy; Berhanu Gudetta; Aida Abashawl; Yohannes Mengistu; Saad B Omer; Abdulhamid Isehak; Solomon Kumbi; Rahel Adamu; Sileshi Lulseged; Roxann Ashworth; Elham Hassen; Andrea Ruff;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-25
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  27     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-08     Completed Date:  2011-12-28     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  823-9     Citation Subset:  IM; X    
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. dpers@jhmi.edu
Data Bank Information
Bank Name/Acc. No.:
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Breast Feeding
Child
Drug Administration Schedule
Drug Resistance, Viral
Ethiopia
Female
Gene Frequency*
Genotype
HIV Infections* / drug therapy,  ethnology,  prevention & control,  transmission,  virology
HIV Reverse Transcriptase
HIV-1 / drug effects,  genetics*,  growth & development
Humans
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical / prevention & control*
Male
Molecular Sequence Data
Molecular Typing
Mutation
Nevirapine* / administration & dosage,  therapeutic use
Pregnancy
Pregnancy Complications, Infectious / drug therapy*,  prevention & control,  virology
Reverse Transcriptase Inhibitors / administration & dosage,  adverse effects*,  therapeutic use
Viral Load / drug effects
Grant Support
ID/Acronym/Agency:
R01 HD057784-01/HD/NICHD NIH HHS; R01 HD057784-02/HD/NICHD NIH HHS; R01 HD057784-03/HD/NICHD NIH HHS; R01 HD057784-04/HD/NICHD NIH HHS; R01-AI38576/AI/NIAID NIH HHS; R01HD057784/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Reverse Transcriptase Inhibitors; 129618-40-2/Nevirapine; EC 2.7.7.49/HIV Reverse Transcriptase
Comments/Corrections

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