Fig. 1

Schematic Designs of Enhanced HIV Susceptibility Nonhuman Primate Models. Three potential study designs and analytic approaches for macaque models of enhanced susceptibility to HIV infection. In panels a and b, the dotted line depicts the experimental arm, subjected to the susceptibility enhancement factor tested in the study. The solid line depicts the control arm. When increased susceptibility is observed, a left-shift would occur in the plots along the x-axis. Note that in the absence of observed susceptibility enhancement, the graphical depiction of the experimental arm would be similar to that of the control arm. a Repeated low-dose exposure infection rates are depicted in Kaplan-Meier survival curves and analyzed by log-rank testing. Survival, or confirmed macaque infections, are plotted on the y-axis, relative to either the number of virus exposures or, in our experience with cycling pigtail macaques, menstrual cycles during exposures. b Dose variation models evaluate the probability of infection (y-axis) relative to decreasing virus dose dilutions (or increasing concentration of challenge virus dose; x-axis). Animal infectious doses required to infect 50 % of the cohorts (AID₅₀) are determined and analyzed by logistic regression statistical models. (*) Vishwanathan, et al. demonstrated lubricant-induced cytotoxicity, but not enhancement of SHIV acquisition risk. c Multiple study designs can use categorical measures of infection probability, such as Fisher’s exact or Chi-square outcome measures to analyze infection rates with and without the proposed enhancement factor