Zack et al.
] proposed a new way to deliver anti-latency agents, like bryostatin, to cells. Following their previous success at incorporating this activator together with Nelfinavir into nanoparticles [34
], they proposed to use vaults, which are cellular organelles, as transporters. Consequently, they engineered vaults to include Bryostatin and found a positive effect in vitro
on reactivation of latent HIV.
Margolis et al.
] presented the first set of results of a trial testing Vorinostat, an HDAC inhibitor. Four patients are currently enrolled in this study which needed a long process of several years for administrative approval. It involves a single 400 mg dose of Vorinostat and looks at HIV expression in resting cells. Initially, the 4 patients were selected as their resting CD4+
cells showed increased viral RNA expression in vitro
following the presence of Vorinostat. From oncologic studies, it is known that the peak of Vorinostat in plasma occurs between 4 and 8 hours after a single administration. A mean increase in vivo
of 4.4 fold of resting CD4+
T cell associated full-length RNA was observed after the administration of 400 mg of Vorinostat and sampling patients at around 6 hours post administration.
Provocative data were presented by Hernandez et al.
] suggesting that, beyond its antiretroviral effect, Maraviroc could activate NF-kB in patients regardless of the tropism of their infecting virus. The protocol "TROPISMCV" (NCT01060618) included naïve HIV-infected patients with CCR5-tropic and non-CCR5 tropic viruses, who received a 10 day monotherapy period of Maraviroc. Activity of NF-kB was detected in 4/6 patients with R5 tropic viruses and in 2/3 patients with D/M tropic viruses. This effect may persist in resting cells after withdrawal of the drug in some patients.
Chen et al.
] showed that the daphnane diterpene Gnidimacrin activated HIV-1 replication and killed persistently-infected cells at picomolar concentrations in vitro
in ACH-1 and U1 cells. In these models, Gnidimacrin was at least 2,000-fold more potent than Prostratin.