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


RESULTS
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.


CONCLUSIONS
Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.
Regoes
Roland R
RR
Department of Biology, Emory University, Atlanta, Georgia, USA. rregoes@emory.edu
Longini
Ira M
IM
Feinberg
Mark B
MB
Staprans
Silvija I
SI
D016915:AIDS Vaccines; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D008954:Models, Biological; D015233:Models, Statistical; D011292:Premedication; D012107:Research Design; D014611:Vaccination
D016915:AIDS Vaccines; D000890:Anti-Infective Agents