Abstract:
:Highly active antiretroviral therapy (HAART) has improved the outlook for the HIV epidemic, but does not provide a cure. The proposed "shock-and-kill" strategy is directed at inducing latent HIV reservoirs, which may then be purged via boosted immune response or targeting infected cells. We describe five novel compounds that are capable of reversing HIV latency without affecting the general T-cell activation state. The new compounds exhibit synergy for reactivation of latent provirus with other latency-reversing agents (LRAs), in particular ingenol-3-angelate/PEP005. One compound, designated PH02, was efficient at reactivating viral transcription in several cell lines bearing reporter HIV-1 at different integration sites. Furthermore, it was capable of reversing latency in resting CD4+ T lymphocytes from latently infected aviremic patient cells on HAART, while producing minimal cellular toxicity. The combination of PH02 and PEP005 produces a strong synergistic effect for reactivation, as demonstrated through a quantitative viral outgrowth assay (qVOA), on CD4+ T lymphocytes from HIV-1-infected individuals. We propose that the PH02/PEP005 combination may represent an effective novel treatment for abrogating persistent HIV-1 infection.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Hashemi P,Barreto K,Bernhard W,Lomness A,Honson N,Pfeifer TA,Harrigan PR,Sadowski Idoi
10.15252/emmm.201708193subject
Has Abstractpub_date
2018-02-01 00:00:00pages
160-174issue
2eissn
1757-4676issn
1757-4684pii
emmm.201708193journal_volume
10pub_type
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