title: Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation.
abstract: Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proviruses without inducing global T cell activation. However, the killing of the infected cells after virus reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4(+) T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Shan
authors.forename: Kai
authors.initials: K
authors.lastname: Deng
authors.forename: Neeta S
authors.initials: NS
authors.lastname: Shroff
authors.forename: Christine M
authors.initials: CM
authors.lastname: Durand
authors.forename: S Alireza
authors.initials: SA
authors.lastname: Rabi
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Joel N
authors.initials: JN
authors.lastname: Blankson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018920:Coculture Techniques; D003588:Cytopathogenic Effect, Viral; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D011533:Proviruses / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology; D014779:Virus Replication