TY - JOUR
T1 - Targeting the Latent Reservoir for HIV-1
AU - Sengupta, Srona
AU - Siliciano, Robert F.
N1 - Funding Information:
We thank Janet Siliciano, Kevin Shenderov, and Andrew Timmons for advice on the manuscript. This work was supported by the NIH Martin Delaney I4C ( UM1 AI126603 ), Beat-HIV ( UM1 AI126620 ), and DARE ( UM1 AI12661 ) collaboratories, by the Johns Hopkins Center for AIDS Research ( P30AI094189 ), and by the Howard Hughes Medical Institute and the Bill and Melinda Gates Foundation ( OPP1115715 ).
Publisher Copyright:
© 2018
PY - 2018/5/15
Y1 - 2018/5/15
N2 - Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir. The development of a successful cure strategy will most likely require understanding the mechanisms that maintain HIV-1 proviruses in a latent state and pathways that drive the proliferation of infected cells, which slows reservoir decay. In addition, a cure will require the development of effective immunologic approaches to eliminating infected cells. There is renewed optimism about the prospect of a cure, and the interventions discussed here could pave the way. Developing a cure for HIV-1 requires understanding the mechanisms of HIV-1 persistence in the latent reservoir. In this review, we discuss historical and recent paradigms in the HIV-1 persistence field as well as novel immunologic and pharmacologic strategies for eliminating this reservoir.
AB - Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir. The development of a successful cure strategy will most likely require understanding the mechanisms that maintain HIV-1 proviruses in a latent state and pathways that drive the proliferation of infected cells, which slows reservoir decay. In addition, a cure will require the development of effective immunologic approaches to eliminating infected cells. There is renewed optimism about the prospect of a cure, and the interventions discussed here could pave the way. Developing a cure for HIV-1 requires understanding the mechanisms of HIV-1 persistence in the latent reservoir. In this review, we discuss historical and recent paradigms in the HIV-1 persistence field as well as novel immunologic and pharmacologic strategies for eliminating this reservoir.
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U2 - 10.1016/j.immuni.2018.04.030
DO - 10.1016/j.immuni.2018.04.030
M3 - Review article
C2 - 29768175
AN - SCOPUS:85046654695
SN - 1074-7613
VL - 48
SP - 872
EP - 895
JO - Immunity
JF - Immunity
IS - 5
ER -