Prime, boost, kick and kill; a functional cure for HIV?

In a study of fifteen HIV-infected patients, a vaccine/drug therapy combo has enabled five participants to bring the virus under control with their own immune systems.

Since its discovery in the 1980s, the road to an HIV cure has been a long and tortuous one. HIV stitches its genome into the chromosomes of T helper lymphocytes, the cells usually in charge of tailoring the immune response towards a particular pathogen. If the T helper cells go into resting mode, transcription of the HIV genome is suppressed by enzymes such as the histone deacetylase. Although stopping replication, this allows HIV to remain undetected by the immune system and to be resistant to anti-retroviral drugs, yet allowing it to emerge later if conditions become favorable.

Another roadblock is the staggering rate at which HIV surface proteins mutate; the genetic variation of HIV in a single person rivals that of the influenza virus in the entire human population in a year. This makes developing vaccines, which equip the immune system with protective antibodies against a certain pathogen, a very hard challenge.

An ongoing study, run by Beatriz Mothe at the IrsiCaixa AIDS Research Institute in Barcelona, is aiming to overcome both of these limitations. During one of their studies HIV patients were given an adenoviral-vectored vaccine containing regions of the HIV proteome known to be conserved in all HIV strains: the ‘prime’.  Patients were then given a ‘boost’, in the form of an MVA-vectored vaccine containing the same components. This regimen aimed to activate T-killer cells specific to the conserved regions of HIV, allowing them to kill infected cells.

However, T-killer cells can only recognize infected cells if HIV is actively replicating inside them. Participants were therefore given romidepsin, an inhibitor of the histone deacetylases which keep HIV in its latent state. This ‘kick and kill’ strategy activates HIV in the resting cells, allowing the T-killer cells to identify and kill them.

Although in most patients the virus rapidly returned after coming off conventional antiretroviral therapy, five have so far been capable of keeping the virus under control without further drugs; one for seven months so far. While encouraging, functional cures in highly publicized cases such as the ‘Mississippi baby’ and ‘Boston patients’ have so far proven to only be temporary.  Therefore it will be quite a long while before the effectiveness of this new treatment can be determined.

(featured image courtesy of NIAID on Flickr)