| Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission. | |
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MedLine Citation:
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PMID: 21241214 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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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:
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Title: AIDS research and human retroviruses Volume: 27 ISSN: 1931-8405 ISO Abbreviation: AIDS Res. Hum. Retroviruses Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-08 Completed Date: 2011-12-28 Revised Date: 2012-09-25 |
Medline Journal Info:
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Nlm Unique ID: 8709376 Medline TA: AIDS Res Hum Retroviruses Country: United States |
Other Details:
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Languages: eng Pagination: 823-9 Citation Subset: IM; X |
Affiliation:
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Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. dpers@jhmi.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Reverse Transcriptase Inhibitors; 129618-40-2/Nevirapine; EC 2.7.7.49/HIV Reverse Transcriptase |
| Comments/Corrections | |
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