Document Detail


Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy.
MedLine Citation:
PMID:  19133804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: We investigated whether there are long-lasting effects of exposure to single-dose nevirapine (sdNVP) treatment on virologic response to nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy among human immunodeficiency virus (HIV)-infected women.
METHODS: An observational epidemiologic study was conducted in Johannesburg, South Africa. Initial and sustained virologic response to NNRTI-based therapy was compared between 94 HIV-infected women who had received sdNVP 18-36 months earlier and 60 unexposed, HIV-infected women who had been pregnant 12-36 months earlier. Viral load was measured every 4 weeks up to week 24 and then every 12 weeks up to week 78. Time to viral suppression (viral load, <50 copies/mL) and confirmed rebound in the viral load (viral load, >400 copies/mL) were compared. Drug resistance was assessed using K103N allele-specific real-time polymerase chain reaction assay and population sequencing.
RESULTS: Almost all women (97.5% of sdNVP-exposed women and 91.3% of sdNVP-unexposed women; P = .21) achieved viral suppression by week 24, and similar percentages of sdNVP-exposed and -unexposed women (19.4% and 15.1%, respectively) experienced viral rebound within 78 weeks after treatment (P = .57). K103N was detected with the K103N allele-specific real-time polymerase chain reaction assay among sdNVP-exposed and -unexposed women before treatment; detection was strongly predictive of inadequate viral response: 60.9% of women for whom K103N was detected in either viral RNA or DNA did not experience viral suppression or experienced viral rebound, compared with 15.1% of women for whom K103N was not detected (P < .001). After treatment, the M184V mutation occurred less frequently among sdNVP-exposed women than among sdNVP-unexposed women, but the frequency of NNRTI-associated mutations was similar between these groups of women with inadequate virologic response.
CONCLUSIONS: Exposure to sdNVP in the prior 18-36 months was not associated with a reduced likelihood of achieving and sustaining viral suppression while receiving NNRTI-based therapy. However, women with minority K103N mutations before treatment had a reduced durability of virologic suppression.
Authors:
Ashraf Coovadia; Gillian Hunt; Elaine J Abrams; Gayle Sherman; Tammy Meyers; Gill Barry; Eloise Malan; Belinda Marais; Renate Stehlau; Johanna Ledwaba; Scott M Hammer; Lynn Morris; Louise Kuhn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America     Volume:  48     ISSN:  1537-6591     ISO Abbreviation:  Clin. Infect. Dis.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-07-09     Completed Date:  2009-08-31     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  9203213     Medline TA:  Clin Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  462-72     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/FJ348474;  FJ348475;  FJ348476;  FJ348477;  FJ348478;  FJ348479;  FJ348480;  FJ348481;  FJ348482;  FJ348483;  FJ348484;  FJ348485;  FJ348486;  FJ348487;  FJ348488;  FJ348489;  FJ348490;  FJ348491;  FJ348492;  FJ348493;  FJ348494;  FJ348495;  FJ348496;  FJ348497;  FJ348498;  FJ348499;  FJ348500;  FJ348501;  FJ348502;  FJ348503;  FJ348504;  FJ348505;  FJ348506;  FJ348507;  FJ348508;  FJ348509;  FJ348510;  FJ348511;  FJ348512;  FJ348513;  FJ348514;  FJ348515;  FJ348516;  FJ348517;  FJ348518;  FJ348519;  FJ348520;  FJ348521;  FJ348522;  FJ348523;  FJ348524;  FJ348525;  FJ348526;  FJ348527;  FJ348528;  FJ348529;  FJ348530;  FJ348531;  FJ348532;  FJ348533;  FJ348534;  FJ348535;  FJ348536;  FJ348537;  FJ348538;  FJ348539;  FJ348540;  FJ348541;  FJ348542;  FJ348543;  FJ348544;  FJ348545;  FJ348546;  FJ348547;  FJ348548;  FJ348549;  FJ348550;  FJ348551;  FJ348552;  FJ348553;  FJ348554;  FJ348555;  FJ348556;  FJ348557;  FJ348558;  FJ348559;  FJ348560;  FJ348561;  FJ348562;  FJ348563;  FJ348564;  FJ348565;  FJ348566;  FJ348567;  FJ348568;  FJ348569;  FJ348570;  FJ348571;  FJ348572
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Substitution / genetics
Anti-HIV Agents / therapeutic use*
Drug Resistance, Viral*
Female
HIV Infections / drug therapy*,  virology*
HIV Reverse Transcriptase / genetics*
HIV-1 / genetics*,  isolation & purification
Humans
Longitudinal Studies
Molecular Sequence Data
Mutation, Missense*
Nevirapine / therapeutic use*
Sequence Analysis, DNA
South Africa
Treatment Outcome
Viral Load
Grant Support
ID/Acronym/Agency:
AI 069470/AI/NIAID NIH HHS; HD 47177/HD/NICHD NIH HHS; R01 HD047177/HD/NICHD NIH HHS; R01 HD047177-01A1/HD/NICHD NIH HHS; R01 HD047177-02/HD/NICHD NIH HHS; R01 HD047177-03/HD/NICHD NIH HHS; R01 HD047177-04/HD/NICHD NIH HHS; R01 HD047177-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 99DK7FVK1H/Nevirapine; EC 2.7.7.49/HIV Reverse Transcriptase
Comments/Corrections
Comment In:
Clin Infect Dis. 2009 Feb 15;48(4):473-5   [PMID:  19133800 ]

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


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