New Billion Dollar Drug Deal, page-24

My recent comments about my scepticism towards viroporin inhibitors in dealing to HIV reservoirs relate to the fact that the term 'HIV reservoirs' gets bandied about without a full understanding of what it actually means. Listening to Biotron pronouncements one might think it was a number of non-lymphocyte cell types that happily happened to have viroporins in their cell membranes and therefore could be a target for BIT225. However, 'HIV reservoirs' is a broader concept than that, and those cell types are only one (small) part of it. Another aspect is that HIV can hang out in the gut lymphatics, which being constantly exposed to antigens from the gut is an area that has to have a certain tolerance to things foreign, and therefore a predilection for shutting down immune responses, which HIV seems to take advantage of. Another aspect is that like many other viruses (CMV, EBV, VZV, HSV being notable examples) HIV can go into a dormant state inside various cell types including memory lymphocytes (very long living cells) and become impervious to all current medications which target viral replication. These viruses can lie dormant for years before popping out and restarting the infection. So 'HIV reservoirs' is a complex concept, and devilishly difficult to defeat. It is likely that viroporin inhibitors would only affect one aspect of this, and with a reasonably low potency in the trials to date I wonder if that is enough.

With regards to Gilead's new drug, that's more of a patent renewal process than a big step forward in treatment - they've simply altered the tenofovir prodrug slightly so that when Truvada goes off patent this version can take over for several more years. I do wonder how much less toxicity there truly is - probably more hype than substance.