The Science of HIV (AL Landay, Section Editor)

Current HIV/AIDS Reports

, Volume 9, Issue 1, pp 81-90

First online:

Role of PD-1 in HIV Pathogenesis and as Target for Therapy

  • Filippos PorichisAffiliated withRagon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School
  • , Daniel E. KaufmannAffiliated withRagon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical SchoolDivision of Infectious Diseases, Massachusetts General HospitalMassachusetts General Hospital East, Ragon Institute of MGH, MIT, and Harvard Email author 

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Abstract

Major advances in Antiretroviral Therapy (ART) have resulted in a dramatic decline in HIV-related deaths. However, no current treatment regimen leads to viral eradication or restoration of HIV-specific immune responses capable of durable viral control after cessation of ART. Thus, there is a need for novel interventions that could complement ART in order to eliminate virus or reach a state of “functional cure.” It has been shown in murine models and humans that the negative co-signaling molecule programmed-death 1 (PD-1) plays an active and reversible role in mediating T-cell exhaustion in chronic infections. This review summarizes recent advances in our understanding of the PD-1 pathway in HIV infection, and the lessons learned from studies in the SIV model and cancer. We discuss the potential of immunotherapeutic interventions targeting PD-1 in order to augment immune responses or facilitate viral eradication. We also present the challenges to therapies targeting immunoregulatory networks.

Keywords

HIV AIDS Chronic viral infection T-cell exhaustion Programmed-death 1 (PD-1) Programmed death-ligand 1 (PD-L1) Programmed death-ligand 2 (PD-L2) CD4 T cell CD8 T cell Monocytes B cell Viral reservoirs Viral eradication Elite controllers Immunotherapy Mucosal immunity