Novel Latency Reversal Agents for HIV-1 Cure - PubMed (original) (raw)

Review

Novel Latency Reversal Agents for HIV-1 Cure

Adam M Spivak et al. Annu Rev Med. 2018.

Abstract

Antiretroviral therapy (ART) has rendered HIV-1 infection a treatable illness; however, ART is not curative owing to the persistence of replication-competent, latent proviruses in long-lived resting T cells. Strategies that target these latently infected cells and allow immune recognition and clearance of this reservoir will be necessary to eradicate HIV-1 in infected individuals. This review describes current pharmacologic approaches to reactivate the latent reservoir so that infected cells can be recognized and targeted, with the ultimate goal of achieving an HIV-1 cure.

Keywords: HIV-1 reservoir; NF-κB; SMAC; STAT5; benzotriazole; disulfiram; ingenol; latency reversal agents; protein kinase C; shock and kill; viral latency.

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Figures

Figure

Figure. Signaling pathways leading to HIV-1 reactivation

Signaling steps involved in viral reactivation by SMAC mimetics, Disulfiram and Benzotriazole derivatives. For details, see main text. Adapted from references and .

References

    1. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997;94:13193–7. - PMC - PubMed
    1. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997;278:1295–300. - PubMed
    1. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997;278:1291–5. - PubMed
    1. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature medicine. 1999;5:512–7. - PubMed
    1. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nature medicine. 2003;9:727–8. - PubMed

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