Animal models for microbicide studies

Abstract

There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.

Figure 1

Comparative histology of the vaginal mucosa of the rhesus macaque (top, A, B) and a naturally cycling women (bottom, C, D). A) Rhesus vagina in natural follicular phase; B) rhesus vagina 30 days after Depo-Provera administration; C) human vagina in follicular phase of the menstrual cycle; D) same vagina in the luteal phase. Since the epithelium of the rhesus vagina is normally thicker than that of women, Depo-Provera is administered to rhesus macaques to synchronize the menstrual cycle and produce a vaginal epithelium more closely resembling that of humans, especially during the luteal stage of the menstrual cycle.

Figure 2

The Kaplan-Meier plots show the remaining fraction of uninfected control animals (y axis) after the number of vaginal exposures to SHIV-162P3 (x axis). The infectious doses (TCID₅₀) used per inoculation in each study are given in the legends to the right of the diagram. DP= Depo-Provera used. Unpublished data (Veazey et al. and Pal et al.) are plotted together with results from the literature (Cheng-Mayer [62]; Lagenaur [63]; Hessell [73]; Bomsel [64]). In the Cheng-Mayer et al. study, doses higher than 300 TCID₅₀ were given after ten exposures, to infect the remaining control animals. They are not included in the diagram.