Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

Autor: Roland R Regoes, Ira M Longini, Mark B Feinberg, Silvija I Staprans
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Zdroj: PLoS Medicine, Vol 2, Iss 8, p e249 (2005)
Druh dokumentu: article
ISSN: 1549-1277
1549-1676
DOI: 10.1371/journal.pmed.0020249
Popis: Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.
Databáze: Directory of Open Access Journals