Theron, Annette J.Anderson, RonaldRossouw, Theresa M.Steel, Helen Carolyn2017-11-302017-11-302017-11-02Theron, A.J., Anderson, R., Rossouw, T.M. and Steel, H.C. (2017) The Role of Transforming Growth Factor Beta-1 in the Progression of HIV/AIDS and Development of Non-AIDS-Defining Fibrotic Disorders. Front. Immunol. 8:1461. DOI: 10.3389/fimmu.2017.01461.1664-3224 (online)10.3389/fimmu.2017.01461http://hdl.handle.net/2263/63388Even after attainment of sustained viral suppression following implementation of highly active antiretroviral therapy, HIV-infected persons continue to experience persistent, low-grade, systemic inflammation. Among other mechanisms, this appears to result from ongoing microbial translocation from a damaged gastrointestinal tract. This HIV-related chronic inflammatory response is paralleled by counteracting, but only partially effective, biological anti-inflammatory processes. Paradoxically, however, this anti-inflammatory response not only exacerbates immunosuppression but also predisposes for development of non-AIDS-related, non-communicable disorders. With respect to the pathogenesis of both sustained immunosuppression and the increased frequency of non-AIDS-related disorders, the anti-inflammatory/profibrotic cytokine, transforming growth factor-β1 (TGF-β1), which remains persistently elevated in both untreated and virally suppressed HIV-infected persons, may provide a common link. In this context, the current review is focused on two different, albeit related, harmful activities of TGF-β1 in HIV infection. First, on the spectrum of anti-inflammatory/immunosuppressive activities of TGF-β1 and the involvement of this cytokine, derived predominantly from T regulatory cells, in driving disease progression in HIV-infected persons via both non-fibrotic and profibrotic mechanisms. Second, the possible involvement of sustained elevations in circulating and tissue TGF-β1 in the pathogenesis of non-AIDS-defining cardiovascular, hepatic, pulmonary and renal disorders, together with a brief comment on potential TGF-β1-targeted therapeutic strategies.en© 2017 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Highly active antiretroviral therapyImmunosuppressionLymphoid fibrosisMacrophagesNon-AIDSdefining defining disordersNon-AIDS defining disordersOrgan fibrosisT Regulatory cellsAntiretroviral therapy (ART)Myocardial infarctionMicrobial translocationTransforming growth factor-β1 (TGF-β1)Obstructive pulmonary diseaseHepatitis-C virusChronic kidney diseaseHIV infected patientsHuman immunodeficiency virus (HIV)Regulatory T-cellsArticle