We speculate that a potential mechanism through which Tat could precipitate HIVAN in HIV-Tg26 mice is by increasing the production and/or activity of TNF-α (Chen et al., 1997), given that high levels of TNF-α are detected in the circulation of HIV-Tg26 mice (De et al., 2002) and that TNF-α worsens the outcome of HIVAN in adult mice (Bruggeman et al., 2011). This evidence concerns the gene TNF and HIV-associated nephropathy.