The prevalence of reduced zidovudine susceptibility in zidovudine-naive, antiretroviral-experienced HIV-1-infected patients.
HIV Med
; 4(4): 305-10, 2003 Oct.
Article
en En
| MEDLINE
| ID: mdl-14525540
ABSTRACT
OBJECTIVES:
There is increasing in vitro and in vivo evidence that reduced zidovudine (ZDV) susceptibility is generated by the selective pressure conferred by other nucleoside reverse transcriptase inhibitors (NRTIs). However, the degree to which this occurs in clinical practice remains unclear. We assessed phenotypic and genotypic resistance in ZDV-naive patients with virological failure on stavudine (d4T)-containing regimens, with particular reference to potential cross-resistance between d4T and ZDV.METHODS:
Patients were identified from a clinical database. Treatment history was confirmed by case note evaluation and discussion with patients. Genotypic and phenotypic analyses were undertaken by Virco (Virco BVBA, Mechelen, Belgium).RESULTS:
Sixty-seven drug-experienced, ZDV-naive patients who underwent a resistance test while failing a d4T-containing regimen were identified. Of these patients, 23% had received three or more NRTIs and 42% at least one non-nucleoside reverse transcriptase (RT) inhibitor; 22% had viruses with reduced d4T susceptibility (>1.8-fold resistance), and 25% had viruses with reduced ZDV susceptibility (>4-fold). The most frequently observed RT mutations were identified. A significant correlation was found between susceptibility to d4T and susceptibility to ZDV (r=0.36; P=0.003), and also between virtual resistance to d4T and that to ZDV (r=0.38; P=0.002).CONCLUSIONS:
A significant minority of d4T-treated, ZDV-naive patients were found to have viruses with reduced ZDV susceptibility, with a variable association with classical ZDV resistance mutations. These data suggest that cross-resistance between d4T and ZDV may involve novel constellations of mutations. Correlations between d4T and ZDV susceptibilities and resistances further support cross-resistance between NRTIs.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Zidovudina
/
Infecciones por VIH
/
Estavudina
/
Inhibidores de la Transcriptasa Inversa
/
Fármacos Anti-VIH
Tipo de estudio:
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
HIV Med
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2003
Tipo del documento:
Article
País de afiliación:
Reino Unido