Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

Vijayakumar Velu, Dyavar D. Shetty, Marie Larsson, Esaki M. Shankar

Research output: Contribution to journalReview articlepeer-review

114 Scopus citations


Virus-specific CD8+ T cells play an important role in controlling viral infections including human immunodeficiency virus (HIV) infection. However, during chronic HIV infection, virus-specific CD8+ T cells undergo functional exhaustion, lose effector functions and fail to control viral infection. HIV-specific CD8 T cells expressing high levels of co-inhibitory molecule programmed death-1 (PD-1) during the chronic infection and are characterized by lower proliferation, cytokine production, and cytotoxic abilities. Although, antiretroviral therapy has resulted in dramatic decline in HIV replication, there is no effective treatment currently available to eradicate viral reservoirs or restore virus-specific T or B-cell functions thatmay complement ART in order to eliminate the virus. In recent years, studies in mice and non-human primate models of HIV infection demonstrated the functional exhaustion of virus-specific T and B cells could be reversed by blockade of interaction between PD-1 and its cognate ligands (PD-L1 and PD-L2). In this review, we discuss recent advances in our understanding of PD-1 pathway in HIV/SIV infection and discuss the beneficial effects of PD-1 blockade during chronic HIV/SIV infection and its potential role as immunotherapy for HIV/AIDS.

Original languageEnglish (US)
Article number14
Issue number1
StatePublished - Feb 8 2015


  • B-cell dysfunction
  • HIV disease
  • PD-1 blockade
  • PD-1 pathway
  • PD-L1 and PD-L2
  • SIV infection
  • T-cell dysfunction

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases


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