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Multisite comparison of anti-human immunodeficiency virus microbicide activity in explant assays using a novel endpoint analysis.
J Clin Microbiol ; 47(11): 3530-9, 2009 Nov.
Article en En | MEDLINE | ID: mdl-19726602
ABSTRACT
Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of human immunodeficiency virus type 1 (HIV-1), such as tonsil, cervical, or rectal tissue. To compare virus growth or the anti-HIV-1 efficacies of candidate microbicides in tissue explants, a novel soft-endpoint method was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, with the method performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft-endpoint method was compared to several other endpoint methods, including (i) the growth of virus on specific days after infection, (ii) the area under the virus growth curve, and (iii) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods, and experimental conditions, using nonparametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when (i) the soft endpoint or another standardized endpoint is used, (ii) drugs and/or virus reagents are centrally sourced, and (iii) the same explant tissue type and method are used. Application of the soft-endpoint method reduces the inherent variability in comparisons of preclinical assays used for microbicide development.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Pruebas de Sensibilidad Microbiana / VIH-1 / Antiinfecciosos Tipo de estudio: Clinical_trials / Evaluation_studies Límite: Female / Humans / Male Idioma: En Revista: J Clin Microbiol Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Pruebas de Sensibilidad Microbiana / VIH-1 / Antiinfecciosos Tipo de estudio: Clinical_trials / Evaluation_studies Límite: Female / Humans / Male Idioma: En Revista: J Clin Microbiol Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos