July 21, 2015
Written by Gus Cairns
This post originally appeared on the NAM website.
The Towards an HIV Cure two-day symposium has become a fixture in advance of the International AIDS Society conferences and this one featured a more varied range of experimental approaches than ever in the search for ways of eliminating HIV infection from the body.
Dr Daniel Kuritzkes of Harvard Medical School, in his opening talk, told the delegates that to some extent the proliferation of different approaches was due to early disappointments in the cure field. We still only have one person, Timothy Ray Brown, who has been cured of HIV and six other cancer patients in whom the same stem-cell transplant therapy had been tried had all died – a reminder that a procedure as exacting as a bone-marrow transplant is never going to be an approach that can be used generally.
The main approach that cure researchers are still working on is the so-called ‘Shock and Kill’ strategy. This uses immune stimulants to induce the cells in which dormant HIV lies hidden – the so-called reservoir cells – to come out of hiding. The hope is then that their activation will in itself lead to their death through natural immune exhaustion; if not, the aim is to target them with directed cell-killing drugs. Without eliminating this reservoir, a small minority of cells capable of spitting out new HIV will remain in the body; experiments have shown that HIV can reappear even when undetectable with the most sensitive viral load tests, as in the case of the ‘Mississippi Baby’.
Since the ‘shock and kill’ strategy has gained wide currency, there have been disappointments: the experimental agents used to reverse so-called ‘latency’ have certainly stimulated virus production by cells – but without resulting in any decrease in the size of the viral reservoir. This appears to be because the drugs chosen – HDAC inhibitors like panobinostat or romidepsin – have other, unforeseen immune effects, including suppressing activity in the very CD8 cells that might be central to the ‘kill’ part of the process.
Nonetheless, Kuritzkes said, for the time being “latency reversal is a necessary, if not sufficient condition in reducing the reservoir of HIV-infected cells”.
He told aidsmap.com: “Most of the interventions that are likely to eliminate infected cells require that the virus is visible to the immune system. The alternative idea, that of permanently suppressing viral production by reservoir cells” (as in the study published last week of a tat inhibitor) “at the moment would seem to involve taking a latency suppressor pill every day instead of antiretroviral therapy. That’s not really a cure.”