Particular emphasis is placed on: (i) T regulatory cells (Tregs) as a major source of the cytokine; (ii) profibrotic destruction of the architecture of secondary lymphoid organs/tissues; (iii) pro-oxidative interactions with macrophages, all three of which drive disease progression; and (iv) the involvement of sustained elevations of TGF-β1 in the pathogenesis of profibrotic, HIV-associated, non-AIDS-defining conditions, specifically those of cardiovascular, hepatic, pulmonary, and renal origin, as well as the possible role of highly active antiretroviral therapy (HAART). This evidence concerns the gene TGFB1 and AIDS.