Despite the rapid progress of the AIDS pandemic, HIV is a surprisingly weak pathogen in vitro. The large difference between in vitro and in vivo infection rates suggests that cofactors absent in vitro but essential for the natural transmission of the virus may be responsible for this discrepancy. A recently identified peptide in human semen, PAP248-286, has emerged as a candidate for the missing cofactor as it dramatically enhances the infectivity of HIV by up to five orders of magnitude. The PAP248-286 peptide fragment has been shown to only induce its synergistic effect with HIV infection when in the form of amyloid fibers. Amyloid formation by PAP248-286 into the active SEVI form is a slow process during which it is susceptible to being degraded and inactivated. Therefore, initiators of this fibrillization process would be an indirect cause of the increase in viral infectivity. For this reason, we have searched for possible inhibitors and enhancers of SEVI amyloid formation including metals, lipids, other amyloids, and polyphenolic inhibitors. The effects of the metals are metal specific, with some enhancing kinetics, while others either inhibit or have little effect. High resolution structures of PAP248-286 and the green tea extract compound epigallocatechin gallate (EGCG) show binding to the monomer subunit through the lysine side-chains and inhibiting fiber growth, which could prove as an effective preventative measure for HIV infection. In contrast, amyloidogenic fibers produced by E. coli are seen to strongly enhance the kinetics of SEVI formation and HIV infectivity, indicating that bacterial infection could enhance the probability of HIV transmission. This phenomenon appears to be quite general and could be an important seeding mechanism for other amyloid proteins.1) Biophysical. Journal (2009), 97(9), 2474-2483.2) Biochemica et Biophysica Acta, Biomembranes (2011), 1808(4), 1161-1169.