The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation
Braz. j. med. biol. res
;
40(12): 1605-1614, Dec. 2007. graf, tab
Article
Dans Anglais
| LILACS
| ID: lil-466741
ABSTRACT
Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 ± 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53 percent of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53 percent of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35 percent of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 ± 14 and 60 ± 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 ± 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Virus de l'hépatite B
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Inhibiteurs de la transcriptase inverse
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Lamivudine
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Hépatite B chronique
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Motifs d'acides aminés
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Résistance virale aux médicaments
Type d'étude:
Essai clinique contrôlé
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Étude observationnelle
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Étude pronostique
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Facteurs de risque
/
Étude de dépistage
Limites du sujet:
Adulte
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Adulte très âgé
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Femelle
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2007
Type:
Article
Pays d'affiliation:
Belgique
/
Brésil
Institution/Pays d'affiliation:
Fundação Faculdade Federal de Ciências Médicas de Porto Alegre/BR
/
Innogenetics NV/BE
/
Universidade Federal do Rio de Janeiro/BR
/
Universidade de São Paulo/BR
/
Universidade do Rio de Janeiro/BR
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