Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

Table 1

Reagents to reactivate HIV-1 from latency.

Latency reactivating reagents	Mechanism	Model	Advantage or disadvantage	Reference
Valproic acid (VPA)	HDAC inhibitors	Clinical	Weak and nonspecific	[87]
Butyric acid	HDAC inhibitors	Clinical	Approved by the FDA	[88]
Vorinostat (SAHA/MK0683)	HDAC inhibitors	ACH-2/U1/J-LAT/resting CD4^+ cells	Approved by the FDA	[39, 89]
Givinostat	HDAC inhibitors	HIV-infected cell lines/Clinical	Superior to VPA	[90]
Panobinostat	HDAC inhibitors	Clinical/HIV-infected cell lines	Lower toxicity	[39, 91]
Apicidin	Histone modification	A10.6 cell line	Synergize with trichostatin A	[92]
Scriptaid	Increasing the acetylation level of histones H3 and H4	Jurkat T cell line	Lower toxicity	[93]
MC1293	HDAC inhibitor	Latency cell lines	Lower toxicity compared to trichostatin A	[47]
M344	HDAC inhibitor	Jurkat T cell	An important role for histone modifications	[94]
As2O3	Affecting the transcription factors and pathways	Jurkat T cell	Synergistically with prostratin or VPA	[48]
OTX015	Activating NF-kappaB	Cell	EC50 value lower than JQ1	[42]
Entinostat (MS275)	Inhibiting HDAC1 and HDAC3	A7 cell	Cytotoxicity lower than SAHA	[95]
Romidepsin	HDAC inhibitor	Clinical/HIV-infected cell lines	Safe	[96]
JQ1	BET inhibitor	Cell lines	A versatile chemical scaffold, binding to its bromodomains	[40]
I-BET151	BET inhibitor	T cells from cART aviremic patients	P-TEFb-releasing agents	[97]
MS417	BET inhibitor	J-Lat cell lines, primary CD4^+ T cells	Releasing BRD4 from the 5′LTR	[97]
Interleukin (IL)-2	Cytokines and chemokines	HIV-1-infected CD4^+ T cells	With limited success
Interleukin (IL)-7	Cytokines and chemokines	Peripheral blood mononuclear cells	Increasing viral production in productively infecting cells without disrupting the latency	[98, 99]
Aza-CdR	DNMT inhibitors	Latently infected cells	An FDA approved drug	[43]
Chaetocin	DNMT inhibitors	Jurkat T cells	Increasing HIV expression without significant toxicity	[100]
HMTi 3-deazaneplanocin A	DNMT inhibitors	Resting CD4^+ T cells or Jurkat T cells	Targeting HKMT enhancer of Zeste 2	[101]
BIX-01294	DNMT inhibitors	Resting CD4^+ T cells or Jurkat T cells	Synergistic action, the first HMT inhibitor used to reactivate HIV-1 in vitro	[102]
Ingenol B	PKC activators	J-Lat A1 cell	More potent than prostratin, SAHA and JQ1	[44]
HMBA	P-TEFb activators	Resting CD4^+ cells	Overcoming barriers to LTR expression	[103]
Disulfiram	Unclassified agents	CD4^+ cells	Clinical trial
ZF-VP64	Specific binding to the 5′-LTR promoter	Latently infected cells	Without altering cell proliferation or cell cycle progression	[45]
TALE1-VP64	Transcription activator-like effector	C11 and A10.6 cells	No distribution of cell proliferation or cell cycle	[46]
Dilazep	Nucleoside transport inhibitor	Jurkat T cell	Synergistically reactivated transcription with valproic acid	[49]