RiaX
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- Jul 2, 2012
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NO NO you need a vaccine per strain not per mutation.
Uhm to be honest I dont have an exact answer for you. One of my professors abandoned his HIV project he works in SA and John Hopikins and the TB HIV research centre (very intelligent guy, I still barely understand his work LOL). He gave a long complex explaination I didnt quite understand fully (difference between professor and bachelor, plus he was showing of that bastid).
But basically the compounds become either too large for protein carriers so they not absorbed orally. The body sees the compound as a threat so it flushes the GIT. Its too polar thus cant absorb across cell membranes. Also the molecules become too large to enter the HIV viron capsid or the CD4+ cell. There are 100s of possibilities though because its an in vitro test its hard to say exactly depends on what they were testing. They use computational chemistry now so they dont have to make compounds over and over and manually test compounds on living things. A computer now has the power to simulate chemical testing, thus only those that are acceptable are actually formulated. The liver also tends to filter out molecules of this nature via enzyme degradation and doesnt allow an active compound to enter the bloodstream. (If you watched the new spiderman movie and they were testing the compound its something like that but not so efficient and perfect and NO WAY as quick lol, just stops living testing and shuts up hippies and yes you can flame me for this but i'd gladly torture millions of mice and bunnies for this cause say what you want - medical calculus let a million die so billions can live, nothing is free even knowledge)
I must go back and ask him when I have the time. I think he made it past the computational stage but not to in vivo testing not sure. Also the compounds become too toxic. See to stop HIV you have to target the following points:
- membrane fusion
- Reverse transcriptase
- Protease
- Block site of infection
As it stands we cant prevent HIV being infectious unless a barrier is used like a condom.
Reverse transcriptase is done by chain termination or steric hinderence (NRTI vs NNRTI) unfortunately the rate at which generations pass they develop resistance to ARVs very fast. Resistance can develop in a matter of days of defaulting. Also making these more potent has too many side-effects the body doesnt like it when you interfere with the DNA and its modalities
Protease inhibitors are very poor, they stop the HIV viron using this enzyme to release its enzymes from the basic proteins found in the capsid however their molecules are fairly large and complex and thus have a poor bioavailablity (saquinavir has about 2% when used alone), thus an extreme dose is required orally or it must be used in combination. Now you have 2 drugs instead of 1 (Alluvia).
You cant block cell fusion on white cells because that would render white cells useless because you stop the entire immunocassade by occupying those specific glycoproteins. Its very complex, just to explain the immune system with a brief synopsis would take you almost 20 pages and you would be very vague in that explaination, thats how complex the immune system is (and why there is no such thing as real immuneboosters). If you consider the target HIV virus the glycoproteins 120 and 41 (which allow cellular fusion) are also extremely complex and SMALL so to fit a ligand there and inhibit it is no simple task (its like building a boeing jet in your garage thats the best way I can make you imagine the difficulty - Hell antivirals cranked me in my university days its no simple task to just understand the science of todays stuff), there are only 2 fusion inhibitors available ATM enfuvirtide and maraviroc. Im not sure if the latter is available in SA yet but I havent encountered enfuvirtide much in the field either so I wont comment on it though I believe its availble as an injection only not sure, and they not very friendly with HAART. An injection twice a day for the rest of one's life, that is not feasable hence the next issue of patient ease and compliance. For HIV infection the real solution HAS to be oral. You cant chemically cure viral infections either, usually the virus is blocked up replicating and it dies on its own or the body developes antibodies that signal the immune system to kill any infected cells via cytokines. We cant kill viruses effectively in real practice like how we kill bacteria with antibiotics. If we had a vaccine then maybe we would have a chance like polio. There isnt a cure for rabbies as well, should you get full blown rabies you are a dead person there is a 0 survival rate for active rabies.
Finally the BIGGEST problem is toxicity, when you increase the efficacy of these agents their toxic effects become more potent hence why you have to have a lot of blood tests before you can start ARVs. I once saw a patient going in to kidney failure WITH ONE SINGLE DOSE OF TENOFOVIR, they didnt do blood tests and initiated therapy blindly which was correct because his CD4+ cell count was "0" diagnosed class 4 WHO HIV postive, no time to wait. So you have to balance the safety with the efficacy, a monumental task considering the agent its going to bind to the subject's DNA (LD50 vs ED50).
sjoe you okes making me revise all this theory LOL least it will keep me sharp. Also keep in mind im trying to be simple and informative at the same time, there is no point giving you these complex explainations that would make you google and wikipedia for a week just to understand, you can do that on your own if you really interested, so dont nit pick.
Also we going too far of topic you welcome to start a thread so we can all discuss the matter, I will try my best to answer them, I got till 2013 before I go back into the field
... unless the world ends on 12/12/12 ROFL 
EDIT
I did say curing HIV isnt that hard above but i meant that in an in vitro setting, in the field of practice with patients thats a whole different story
Uhm to be honest I dont have an exact answer for you. One of my professors abandoned his HIV project he works in SA and John Hopikins and the TB HIV research centre (very intelligent guy, I still barely understand his work LOL). He gave a long complex explaination I didnt quite understand fully (difference between professor and bachelor, plus he was showing of that bastid).
But basically the compounds become either too large for protein carriers so they not absorbed orally. The body sees the compound as a threat so it flushes the GIT. Its too polar thus cant absorb across cell membranes. Also the molecules become too large to enter the HIV viron capsid or the CD4+ cell. There are 100s of possibilities though because its an in vitro test its hard to say exactly depends on what they were testing. They use computational chemistry now so they dont have to make compounds over and over and manually test compounds on living things. A computer now has the power to simulate chemical testing, thus only those that are acceptable are actually formulated. The liver also tends to filter out molecules of this nature via enzyme degradation and doesnt allow an active compound to enter the bloodstream. (If you watched the new spiderman movie and they were testing the compound its something like that but not so efficient and perfect and NO WAY as quick lol, just stops living testing and shuts up hippies and yes you can flame me for this but i'd gladly torture millions of mice and bunnies for this cause say what you want - medical calculus let a million die so billions can live, nothing is free even knowledge)
I must go back and ask him when I have the time. I think he made it past the computational stage but not to in vivo testing not sure. Also the compounds become too toxic. See to stop HIV you have to target the following points:
- membrane fusion
- Reverse transcriptase
- Protease
- Block site of infection
As it stands we cant prevent HIV being infectious unless a barrier is used like a condom.
Reverse transcriptase is done by chain termination or steric hinderence (NRTI vs NNRTI) unfortunately the rate at which generations pass they develop resistance to ARVs very fast. Resistance can develop in a matter of days of defaulting. Also making these more potent has too many side-effects the body doesnt like it when you interfere with the DNA and its modalities
Protease inhibitors are very poor, they stop the HIV viron using this enzyme to release its enzymes from the basic proteins found in the capsid however their molecules are fairly large and complex and thus have a poor bioavailablity (saquinavir has about 2% when used alone), thus an extreme dose is required orally or it must be used in combination. Now you have 2 drugs instead of 1 (Alluvia).
You cant block cell fusion on white cells because that would render white cells useless because you stop the entire immunocassade by occupying those specific glycoproteins. Its very complex, just to explain the immune system with a brief synopsis would take you almost 20 pages and you would be very vague in that explaination, thats how complex the immune system is (and why there is no such thing as real immuneboosters). If you consider the target HIV virus the glycoproteins 120 and 41 (which allow cellular fusion) are also extremely complex and SMALL so to fit a ligand there and inhibit it is no simple task (its like building a boeing jet in your garage thats the best way I can make you imagine the difficulty - Hell antivirals cranked me in my university days its no simple task to just understand the science of todays stuff), there are only 2 fusion inhibitors available ATM enfuvirtide and maraviroc. Im not sure if the latter is available in SA yet but I havent encountered enfuvirtide much in the field either so I wont comment on it though I believe its availble as an injection only not sure, and they not very friendly with HAART. An injection twice a day for the rest of one's life, that is not feasable hence the next issue of patient ease and compliance. For HIV infection the real solution HAS to be oral. You cant chemically cure viral infections either, usually the virus is blocked up replicating and it dies on its own or the body developes antibodies that signal the immune system to kill any infected cells via cytokines. We cant kill viruses effectively in real practice like how we kill bacteria with antibiotics. If we had a vaccine then maybe we would have a chance like polio. There isnt a cure for rabbies as well, should you get full blown rabies you are a dead person there is a 0 survival rate for active rabies.
Finally the BIGGEST problem is toxicity, when you increase the efficacy of these agents their toxic effects become more potent hence why you have to have a lot of blood tests before you can start ARVs. I once saw a patient going in to kidney failure WITH ONE SINGLE DOSE OF TENOFOVIR, they didnt do blood tests and initiated therapy blindly which was correct because his CD4+ cell count was "0" diagnosed class 4 WHO HIV postive, no time to wait. So you have to balance the safety with the efficacy, a monumental task considering the agent its going to bind to the subject's DNA (LD50 vs ED50).
sjoe you okes making me revise all this theory LOL least it will keep me sharp. Also keep in mind im trying to be simple and informative at the same time, there is no point giving you these complex explainations that would make you google and wikipedia for a week just to understand, you can do that on your own if you really interested, so dont nit pick.
Also we going too far of topic you welcome to start a thread so we can all discuss the matter, I will try my best to answer them, I got till 2013 before I go back into the field
... unless the world ends on 12/12/12 ROFL EDIT
I did say curing HIV isnt that hard above but i meant that in an in vitro setting, in the field of practice with patients thats a whole different story
