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HIV Health and Treatment Issues >> Treatment & Side Effects

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ethan_hines
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Reged: 02/09/09
Posts: 17
Interferon and Hiv
      #244591 - 02/16/09 08:47 AM

Why doesn't pegylated Interferon work the same way with Hiv as it does with HVB/C?. Isn't Interferon very important in fighting RNA virus infections which Hiv is one of? How does Hiv get around its defence?

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sick_of_fuckwits
Master

Reged: 01/26/09
Posts: 145
Re: Interferon and Hiv new
      #244592 - 02/16/09 09:03 AM

HIV transcribes its RNA into DNA and is therefore a retrovirus - not a ribovirus, a subset of RNA viruses that specifically excludes retroviruses - which is why all anti-HIV drugs belong to a class of drugs known as antiretroviral drugs.

Retroviruses are part of a larger family of viruses known as reverse transcribing viruses, which also includes hepatitis B (explaining why some anti-HIV drugs can be more effective than interferon alfa when treating that one particular form of viral hepatitis).

Interferon alpha is a cytokine which stimulates cytotoxic / CD8 / killer T cells, but isn't effective against retroviruses because CD8 cell activation isn't generally the real problem when you are infected with a retrovirus such as HIV. That said, some other types of cytokines can be used to increase your CD4 / helper T cell count; but, as two papers presented at last week's Conference on Retroviruses and Opportunistic Infections showed, to little therapeutic effect and with a very heavy burden of side-effects.

And just to add to the confusion:
  • HIV is an RNA virus, a retrovirus and a reverse transcribing virus
  • Hepatitis B is an RNA virus, a ribovirus, a reverse transcribing virus and a hepacivirus
  • Hepatitis C is an RNA virus, a ribovirus and a hepacivirus
.. so they all share some traits and all mutate quickly, but are different enough that they respond to different treatment strategies. Interferon alpha is a treatment option for riboviruses, but not RNA viruses generally.

Congratulations if that makes sense .. but if your next question is why isn't hepatitis B a retrovirus? don't even dare to think that I am going to go there

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ethan_hines
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Reged: 02/09/09
Posts: 17
Re: Interferon and Hiv new
      #244627 - 02/17/09 03:11 PM

Thank You that was a great explanation. I do have a follow up question thou: If CD8+ Tcells are mainly responsible for killing those cells that are infected with HIV (and other viruses), if a person was virologically suppressed (<50cps/ml) and given Interferon Alpha to increase/stimulate cd8+ production, could that not allow the immune system to clear the infection?

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sick_of_fuckwits
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Reged: 01/26/09
Posts: 145
Re: Interferon and Hiv new
      #244628 - 02/17/09 03:51 PM

No. As I said, CD8 cell activation isn't generally the real problem - most of us here with HIV will have a disproportionately large number of CD8 cells as it is, but fewer CD4 cells to act as ringmasters .. besides with treatment target achieved the plasma level is already down to <50 copies/ml and the entire life-cycle of the little buggers is only 1.5 days or so, so there are plenty of CD8 cells to do what they have to do.

It is the vast reservoirs of dormant HIV scattered in around the body - which can stay in that state for up to 70 years - that are the problem. That dormant HIV is invisible to the human immune system until it re-activates; so you can pump as many CD8 cells in there as you like, but it just wont make any difference. That is why one of the most heavily researched areas of HIV is to do with finding a way to activate all the dormant HIV over a relatively short period of time.

Think of dormant HIV as a whole fleet of Klingon Birds of Prey with their cloaking devices engaged. CD8 cells are the photon torpedoes and you have a whole hold full of them. You have plenty of photon torpedoes, but you can't find your targets to fire them at. A few uncloak every so often and they are easily dealt with .. but you have to stay at battle stations all the time, so your crew starts getting tired and inefficient. What you need is a mass-uncloaking device, not more torpedoes, so you can get the battle over and done with and won.

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ethan_hines
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Reged: 02/09/09
Posts: 17
Re: Interferon and Hiv new
      #244636 - 02/17/09 06:55 PM

Of the regulatory proteins (Tat, Nef, and Vif) which one do you think contibutes to this "cloaking device"? And can proteins be inhibited? do they have active sites like the enzymes (RT,INT,PR) do?

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sick_of_fuckwits
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Re: Interferon and Hiv new
      #244642 - 02/18/09 02:07 AM

Dude, you really are pushing your luck now.

If you are informed enough to understand the determinants of HIV - which most doctors and people who have been living with HIV for many years don't even understand - then you certainly don't need me to explain the finer points of genes and proteins .. and you most certainly aren't someone who needs to be here asking am I infected type questions. Whatever game you are playing here, it has now run its course; because as far as I am concerned you really are taking the piss, have now strayed miles beyond the limits of my patience and are seriously abusing any worried well allowances I may mistakenly have chosen to afford you.

Doing some basic checking on you, I can see that you have been lurking in HIV forums since at least September of last year - by which time you were already banging the boring and utterly irrational big pharma conspiracy not being in the best interests of people living with HIV drum - so, whatever your issues are, either declare your hand honestly or stop abusing the generosity of people who are genuinely trying to help those in real distress and need.

For the benefit of anyone who doesn't understand what I am talking about, check out the comments on Uh, no at Paul's POZ Blog.

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ethan_hines
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Reged: 02/09/09
Posts: 17
Re: Interferon and Hiv new
      #244653 - 02/18/09 12:28 PM

I don't see anything wrong with asking pertinent questions in the right forum. I can't keep asking "the experts" and there is no other place to discuss the technical aspects of the virus. I'm not a virologist, or MD. I don't understand why people think I have malevolent attitude. It seems wherever I go I burn bridges, for doing nothing wrong. I ask intelligent questions in the right form mind you, and I get chastised. I started my questions in the "Am I infected" forum because I didn't want to offend anyone for posting in the wrong place as I'm sure you know are the rules and regulations at poz.com and I'm sure you know I was banned for simply for posting out of the "Am I infected form and for not continuing my questions in the same thread, I thought things would be different here. As for the comment I made on Paul's blog I was stating that I do see how pharmaceutical companies seem more interested in profit then genuinely bringing good drugs to market, TNX-355 is the only truly dual-tropic co-receptor inhibitor, and its development will be delayed from the takeover

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sick_of_fuckwits
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Reged: 01/26/09
Posts: 145
Re: Interferon and Hiv new
      #244654 - 02/18/09 01:46 PM

Well no I don't know that you were banned from AIDSmeds / POZ; because these days I have more sense than to hang out there - but yeah, I can well imagine that you wouldn't have gone down too well with their moderation Gestapo.

I am not suggesting that you have a malevolent attitude / agenda .. but I do want to know why you are asking. What exactly is your situation? Are you poz?. Are you worried about being infected? How many times have you tested? Over how long a period? Stuff like that. It is bloody hard work explaining some of the more technical stuff, and sometimes it is knowledge that can do far more harm than good. It can feed anxiety and paranoia .. and very often counselling is a much better option if you have already tested to excess. So much so that I will say here and now that the internet is the worst place you can be hanging out if you are worried about being infected with HIV. If people are trying to stop you going round in circles, it isn't necessarily that you have burnt bridges - they may just be worried that it isn't good for you.

If you have a good reason for wanting to understand this stuff, then I will happily spend the time explaining - it might be in private though - but I'm not seeing that at the moment. Yes your questions are intelligent. Too bloody intelligent and they look like they should be on some sort of exam paper - and with all due respect it isn't normal for someone who isn't even HIV-positive to be asking this sort of stuff - and you have to understand why that looks and feels a little strange .. to the point where I have even started looking for signs of Asperger's syndrome in your writing Try to understand that .. and that as much as anything I am thinking of you (and, to be fair, that probably goes for the people over at POZ too).

As for the drug thing: most drugs are developed by small laboratories and sold on up the food chain to companies that have the clout to take the risks and manoeuvre them through the regulatory hurdles and take them to market. The small companies need the cash flow to fund new projects and far from slowing anything down it actually keeps the small innovative labs working and increases a drug's chance of making it to market.

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hopefulone
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Reged: 12/05/08
Posts: 130
Loc: NY, NY
Re: Interferon and Hiv new
      #244655 - 02/18/09 02:16 PM

i am intrigued by his question now and the whole piece about how knowing might do more harm than good. i am confused.

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sick_of_fuckwits
Master

Reged: 01/26/09
Posts: 145
Re: Interferon and Hiv new
      #244656 - 02/18/09 02:39 PM

Hopeful,

It is just that it can feed obsessions and make you look for ever more obscure reasons not to trust antibody test results. If, by answering questions, you are feeding an obsession; then it is sometimes kinder just not to answer the questions. It isn't that there are deep and dark secrets about HIV that would scare you

Ethan has been hanging around HIV forums long enough that he should have a conclusive antibody test result and should be able to move on. I don't want to be responsible for feeding whatever is stopping him from doing moving on - yet he asking questions at a level that most people with HIV don't ever get around to asking. I just can't see that it is healthy.

--------------------
There's probably no God. Now stop worrying and enjoy your life.

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ethan_hines
Member

Reged: 02/09/09
Posts: 17
Re: Interferon and Hiv new
      #244695 - 02/19/09 12:53 PM

I will be the first to admit I have an unnatural obsession with this subject, and yes I have been spending a great amount of time researching this subject. Why? To get to the bottom of this virus. To understand how it differs from other viruses that the body can potentially clear (Hep B/C). Have I gotten physiological help? Sort of , I was being followed by a counselor while it was still up in the air. I tested negative on three separate occasions (6wks, 3mo, 6mo) however I took PEP 36hours after a percutanious exposure to a known positive. I was never offered RNA testing or another diagnostic test other then Antibody's (HIV and Hep B/C) no p24,no cd4, no esr, nothing. Do I think I am infected? About 90% sure I am not, I know it's almost unheard of seroconversion past 6mo but I truly feel unless I have that Proviral RNA test I can never be sure. The only symptom I am continuously having is night sweats every night. Yes I know they can be caused by a variety of things from antidepressants to panic attacks. I know it’s a "non-specific" symptom but tell me what symptom of HIV is specific; there are none. Seven days post exposure I had a low grade fever followed by a mononucleotic feeling. I just feel like the medical staff didn't take a vested effort to diagnose me, sure they did everything by the book, but I'm still left with this feeling that there is something left unsaid.

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sick_of_fuckwits
Master

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Posts: 145
Re: Interferon and Hiv new
      #244696 - 02/19/09 01:39 PM

I feel for you.

As you correctly observe; from a technical point of view, everything has been done by the book - but perhaps the reassuring human touch could have been missing.

I will try to take this stage by stage - but before I even start I will lay my cards on the table and say that I have never been surer of a negative result.

A P24 is pointless - you are months beyond the point at which that is of any use at all.

PCR is a possibility if, subject to the reservations I have expressed elsewhere, you genuinely feel it would help to put that remaining 10% of doubt behind you and not get freaked by a preliminary false-positive (although, in all honesty, you are probably far enough down the line that this becomes less of a likelihood).

Following any sort of intimacy (not necessarily sexual) - especially with someone who you already know was immunocompromised - it is not inconceivable that you would have picked up some sort of infection other than HIV. I am not necessarily talking about the sort of infections that we generally think of as being sexually transmitted - it could be anything and infectious mononucleosis (glandular fever) certainly wouldn't be an implausible candidate.

This is delving a lot deeper into the personal confessions stakes than I would generally go, but every time I have sex with someone I have never had sex with before, I will get a sore throat and a short mild flu-like illness. That is nothing new and goes back to before I became HIV-positive. It is just a part of the reality that we all walk around with all manner of mostly harmless viruses and infections, and when we come into contact with a new one, our immune system kicks in, gives us a reaction and clears whatever infection without any outside assistance. Most of the time in most people it isn't even noticeable; but in some of us it is .. and in my case it is every bloody time. One of those instances with me was Hepatitis B, which came and went completely unnoticed along with the pesky HIV thing .. and I only know about it because I have a natural immunity to it.

You also have to consider the impact of the PEP. For that not to have given you at least some symptoms would be a minor miracle. Is it not possible that could be responsible for some of your symptoms? Fever and fatigue - both also symptoms of ARS and mononucleosis - are definitely classic side-effects of PEP too.

And there is stress - I am sure I don't need to tell you what that can do.

Even if we rule all of those things out of the picture, if any of the symptoms you experienced were ARS related, then you would have seroconverted by now. You aren't going to experience ARS and not have seroconverted more than six months later - that is just a physical impossibility that doesn't even come with any of the qualifications which say that it is theoretically possible to seroconvert more than six months after exposure. It can not happen.

So we are down to two final options: PEP did what it does 70% of the time and stopped an infection dead in its tracks (very doubtful) .. or whatever you experienced was just an unrelated coincidence.

I will be honest and tell you that if you were one of my clients I would be arranging for you to take a PCR test - but I will also be honest and tell you that it would be for your peace of mind, knowing that there was no medical need to take one; because there is just no way on this earth that you could be HIV-positive.

I know that there is every probability that none of that helps you, but that is my take on your situation.

Ruairi x

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sick_of_fuckwits
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Reged: 01/26/09
Posts: 145
Re: Interferon and Hiv new
      #244702 - 02/19/09 03:22 PM

Quote:

Of the regulatory proteins (Tat, Nef, and Vif) which one do you think contibutes to this "cloaking device"? And can proteins be inhibited? do they have active sites like the enzymes (RT,INT,PR) do?



You are taking my analogy of a cloaked Bird of Prey a little too literally. There is no cloaking device. It is simply the inactivity of dormancy which means that the immune system doesn't recognise a cell as being infected with HIV.

Now, if you are thinking that you maybe aren't testing positive because all your HIV is dormant, then I can assure you that it doesn't work like that. You have to have a pretty massive invasion of HIV before it spreads to the tissues in which it can enter the dormant state - and when I say massive I really do mean so massive that you are way beyond the point of seroconversion and developing antibodies.

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ethan_hines
Member

Reged: 02/09/09
Posts: 17
Re: Interferon and Hiv new
      #244714 - 02/20/09 01:55 PM

Thank you Ruairi,You are the first person I've communicated with who truly appreciates my situation. I intend to press my GP for a pcr test (with all the risks of a false-positive). I'll keep you posted.

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allangering
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Reged: 07/04/09
Posts: 46
Re: Interferon and Hiv new
      #246597 - 07/17/09 03:32 AM

Interferons are naturally occurring proteins secreted by cells in response to infection, and they serve multiple roles as antiviral, antitumor, and immune stimulating agents. The three major classes of interferon have been synthesized, and each is being studied in various applications for the treatment of HIV and AIDS.
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