New, weird, out-of-left-field, ideas-- we need them to stop HIV.
This one makes sense, in retrospect, but I wouldnt have thought to try what these folks did:
Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection
Background info: HIV loves to rip through CD4+ T-cells in gut-associated lymphoid tissue. Early in infection, HIV tears those cells up, and anything HIV doesnt kill, it digs in as a latent reservoir to pop out more babby viruses later. Doesnt matter if you ultimately take anti-retrovirals, the damage is done early in infection, and things never go back to 'normal'. (more info).
Maybe you can stop/limit HIV infection by keeping GALT CD4+ T-cells from running around like chickens with their heads cut off?
But how would you even go about doing that?
Some immune cells, like CD4+ T-cells, roll round your body. Where they are needed, cells will express integrins to slow down their rolling. The immune cell then smooshes itself through the cell barrier to get where it needs to go. Remember that animation from XVIVO a while back?
So, maybe stop CD4+ T-cells from moving around by blocking the interactions between the cell and the integrins.
It turns out there is already a drug in clinical trails that can do that: An anti-alpha4beta7 antibody, AMG 181/MEDI-7183, made by Astrazeneca (more info about these drugs here-- I think this is OA).
Astrazeneca is using it for Crohns disease and ulcerative colitis, but no reason it cant be tried with HIV, right?
Well, apparently, this idea kinda works.
When monkeys were given monkey-version of the anti-a4b7 antibody, then vaginally challenged with SIV, 10 of 12 control monkeys got infected, whereas 6 of 12 treated animals got infected. And the treated animals only got infected after repeated challenges-- early in the experiment (weak 5), only 1 of 12 got infected, whereas the 10 infected control animals were all infected by then. They had to keep exposing the animals to virus over and over to get the number up to 6 in the treated animals.
Furthermore, the treated infected animals were able to keep their CD4+ T-cell levels up, while the untreated animals had their numbers tank. As to what this could mean for disease prognosis if someone takes this treatment, but still becomes infected, they noted that in their previous work with this antibody for 'treating' SIV in monkeys:
Notably, whereas 10 of 12 controls died of AIDS within 2 years, all ten treated animals remained
healthy with CD4+ T cell counts >500/µl 5 years after infection.
So, maybe, if you take this treatment, but you still get infected, you might progress from HIV-->AIDS very slowly, if at all.
Remember, folks, these are studies in a few dozen monkeys!
We are a loooong way from this being in people, even with Phase 1 clinical trials already completed.
We have no clue *HOW* this therapy works. They have great ideas-- In the treated but infected animals, HIV was hanging out at the site of infection, and was found less frequently in the GALT. Maybe the treatment kept new targets from the site of infection? Maybe it kept infected CD4+ cells from creeping around and infecting other CD4+ T-cell hot-spots? Maybe the antibody straight-up interferes with SIV binding to target cells?
We dont know what dose to give people. We dont know whether it HAS to be injected, or whether it could work as a local gel. We dont know what potential side-effects there are (what if you are on this treatment, and get the flu?). We dont know whats up with the viruses that could overcome the treatment. We dont know how to give this treatment to people who are already infected (how do anti-retrovirals play into this? would PREP compliment this, or not?).
We dont know a lot.
But its something that seems to kinda work, it doesnt target the virus (a ticking time-bomb with HIV-- works for a while, then HIV figures out a way around it), and its passed Phase I clinical trials already.
We always need new weapons against HIV-- I hope this one pans out.
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Well, you can't treat HIV patients with natalizumab.
Because of the risk of PML (as it originally found in AIDS patients, but is commonly associated with natalizumab as it suppresses immunosurvellience of the brain), but vedolizumab doesn't cause it in more than 3000 patients in clinical trials for 6 years.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038524/ (safety and tolerability of vedolizumab)