Talk:Zidovudine/Archive 2

Archive 1

Archive 2

Archive 3

In vitro

I've reverted this edit, which belabored the fact that the relative binding affinities of AZT for HIV and human cells are based on in vitro data. Of course, all affinity measurements are made in vitro, so it seems redundant to belabor the point. I'm not aware of any scientific data indicating that the affinity models for AZT don't hold up in vivo, again suggesting that this is an irrelevant distinction. I'd welcome other opinions on the matter. MastCell ^Talk 03:38, 25 March 2009 (UTC)

I have reverted this same edit, by this same point-making editor, in the past. Keepcalmandcarryon (talk) 23:29, 25 March 2009 (UTC)

I now suggest the following and welcome reader comment:

Superscripted footnote-tags should be created for each of the following six scientific classifications, all of them found in Wikipedia: in vitro, in vivo, in situ, ex vivo, in utero, and even in silico. Need: to uniformly and concisely impart to the reader the specific nature of the experiment being referenced by footnote. Implementing this change would also probably effect a needed review of references.Eye.earth (talk) 03:24, 26 March 2009 (UTC)

That information is already contained in the footnoted reference, where any modestly enterprising reader can find it just as easily as they can click a wikilink. Of course, you're free to take up that suggestion at the Medicine WikiProject, or the Village Pump, or any number of appropriate areas. In the meantime, please stop edit-warring. MastCell ^Talk 05:05, 26 March 2009 (UTC)

OK. In the meantime, please stop edit-warring. Readers, the sentence in question has two footnotes. The one claiming a 100-fold affinity doesn't contain in vitro in its title. Inserting in vitro in the text simply emphasizes the in vitro nature of the 100-fold affinity. It is hardly a "nonsensical descriptor" as MastCell claimed, and that an administrator could make such a claim makes me shudder.

It's obvious that MastCell wants inattentive readers to assume that the 100-fold affinity exists in vivo. The affinity of course doesn't hold in vivo and I don't know why this shouldn't be clear in the text. —Preceding unsigned comment added by Eye.earth (talk • contribs)

According to whom doesn't the affinity hold in vivo? According to conjecture by AIDS denialists, who of course haven't researched the matter. No reliable sources have been presented to support the idea that the relatively greater measured affinity of AZT for HIV RT than for cellular enzymes is magically reversed in a patient's body. As I note in my edit summary, Eye.earth's edits are like claiming that the mass of a water molecule is 18 daltons only in vitro. Keepcalmandcarryon (talk) 14:16, 26 March 2009 (UTC)

AZT does not destroy the HIV infection, but only delays the progression of the disease and the replication of virus, even at very high doses. During prolonged AZT treatment HIV has the ability to gain an increased resistance to AZT by mutation of the reverse transcriptase. A study showed that AZT could not impede the resumption of virus production, and eventually cells treated with AZT produced viruses as much as the untreated cells. To slow the development of resistance, physicians generally recommend that AZT be given in combination with another reverse transcriptase inhibitor and an antiretroviral from another group, such as a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.

That was fun. If you agree that I've made my point, please reinstate my edit. If not, this AIDS denialist who of course hasn't researched the matter awaits your reply. Eye.earth (talk) 03:24, 27 March 2009 (UTC)

And that's exactly what this talk page is not: a forum for denialism, supported by synthesis. When you present a reliable source with evidence that in vitro comparisons of AZT affinity for HIV RT and cellular enzymes do not hold in vivo, we can change the article. Until then, no amount of conjecture on your part will suffice. Keepcalmandcarryon (talk) 14:16, 27 March 2009 (UTC)

Feeling as you do about it, I'm surprised you haven't changed it. Perhaps my edit will help. —Preceding unsigned comment added by Eye.earth (talk • contribs) 16:38, 27 March 2009 (UTC)

In the interests of clarity, I've reposted the substance of my above reply (at 03:24, 27 March 2009 (UTC)), this time with the hypertext formatting left in.

"AZT does not destroy the HIV infection, but only delays the progression of the disease and the replication of virus, even at very high doses. During prolonged AZT treatment HIV has the ability to gain an increased resistance to AZT by mutation of its reverse transcriptase. A study showed that AZT could not impede the resumption of virus production, and eventually cells treated with AZT produced viruses as much as the untreated cells. To slow the development of resistance, physicians generally recommend that AZT be given in combination with another reverse transcriptase inhibitor and an antiretroviral from another group, such as a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor."

So AZT has no therapeutic in vivo affinity for the viral RT. The affinity is strictly in vitro, which is to say, temporary. By inserting in vitro into the text, this critical point is clarified for the casual reader. However, if anyone has good reason to disagree with the above paragraph, they should feel free to rewrite it. It's in the article itself, under "Viral resistance". Eye.earth (talk) 14:56, 31 March 2009 (UTC)

One of the reasons that we require verifiable material from reliable sources is that individual, pseudonymous editors are a mixed bag. In this case, you are basing your edits on an incorrect understanding, which may explain why you've (apparently) been unable to find any independent, reliable sources backing the distinction you'd like to draw. You also seem to be confused about the meaning of the term in vitro - it does not mean, nor imply, "temporary".

You state that "AZT has no therapeutic in vivo affinity for the viral RT." That's incorrect (and oddly phrased). Of course AZT binds to viral reverse transcriptase in vivo - that's the mechanism of its well-documented efficacy against HIV. Rather than debat this point endlessly, I'll go back to requesting that you a) stop edit-warring to insert material unsupported by the other editors of this article, and b) produce an actual reliable source making the point you'd like to advance. MastCell ^Talk 19:18, 31 March 2009 (UTC)

Mastcell, simply insert in vivo in place of my in vitro. After all, the stated affinity is either: 1) in vitro, 2) in vivo, or 3) both. State explicitly which of the three it is and then cite a reference justifying your conclusion. I've done my part by stating in vitro. My justification is in the two footnotes found at the end of the sentence in question referencing two in vitro experiments. If the therapeutic mechanism is as "well-documented" as you say it is, just cite one of those documents. I'm curious as to whether it will address the matter of viral resistance. I predict that it won't. Eye.earth (talk) 15:38, 1 April 2009 (UTC)

I hate to be circular, but I don't think you're hearing me. All affinity measurements are in vitro. That's assumed when you talk about affinity in a quantitative sense. It doesn't really make sense to stick the phrase in here, any more than it makes sense to say that the mass of a water molecule is 18D "in vitro". I'll admit I'm a bit jaundiced by your obviously fuzzy grasp of the relevant material, as well as by the fact that virtually your entire Wikipedia career has been devoted to inappropriate advocacy of AIDS denialism, so maybe I'm making a mountain out of a molehill here. Still, it seems unecessarily redundant at best, and misleading at worst - hence my objection. MastCell ^Talk 21:26, 1 April 2009 (UTC)

Are you saying now that the affinity doesn't necessarily hold in vivo? The whole point of my inserting in vitro is to emphasize to casual readers (who don't necessarily know the clinical definition of "affinity") that the asserted affinity of AZT for HIV's RT is derived from in vitro experiments and doesn't necessarily apply in vivo. The issue is clarity for a general readership, which you described above as a "mixed bag." It is indeed a mixed bag, which is why elementary clarity is good practice.

On the other hand, if you are continuing to imply an in vivo affinity, then don't imply it anymore. State it as fact in the disputed sentence and include a reference asserting such an affinity. Eye.earth (talk) 05:02, 2 April 2009 (UTC)

I'm not really interested in a semantic debate, and I'm particularly not interested in rewarding your editing behavior, which seems to consist of slow edit-warring to try to force a change with which multiple other editors disagree. The article makes clear that resistance develops with prolonged use; that is a separate issue from the relative affinities of zidovudine for mammalian and viral enzymes. All reliable sources treat these issues separately. I'm not sure why you're so insistent on synthesizing this distinction, but a) your arguments haven't been particularly convincing as they are based on editorial semantics rather than reliable sources, and b) your editing conduct is a direct barrier to convincing anyone to collaborate with you, as the numerous warnings and admonitions on your talk page should probably make clear. MastCell ^Talk 20:24, 2 April 2009 (UTC)

This entire discussion is about my insert of the phrase in vitro into the disputed sentence. I did so to emphasize to casual readers that the asserted 100-fold affinity of AZT for HIV RT is derived from in vitro experiments, specifically the two referenced as footnotes. As these are reliable sources directly referenced, my edit is hardly an act of synthesis. Note that I don't say in the article that the asserted affinity doesn't hold in vivo. You are free to make such an in vivo assertion as long as you back it up with a good-source reference. Why haven't you done so if you feel the affinity holds in vivo?

That's a rhetorical question. There are no studies asserting an in vivo affinity for HIV RT. AZT's affinity in vivo or in vitro is to substitute for thymine and nothing else. That's how it was designed in 1964 and that's what it does today, true to form. If it can replace thymine in viral RT, fine. When mutation in that RT makes the substitution too difficult (which is what happens) those thymine analogues are free to substitute for natural thymine found in cellular DNA, which they would be doing anyway in cells not infected by HIV, i.e., the majority of cells in the body. Engineering any degree of affinity for viral RT in vitro is a task dependent on the ingenuity of the experimenter and (no doubt) certain practical limitations. Both are inapplicable in vivo, where doctors can only watch as the AZT chemotherapy does exactly what it is supposed to do: kill any replicating cell it comes into contact with, HIV-infected or not, period.

None of which changes the fact that inserting in vitro in the disputed sentence simply emphasizes that the conclusion of AZT's 100-fold affinity for HIV RT is based on the two footnoted, in vitro experiments (only one of which contains the phrase in vitro in its title). My edit prevents an unconscious, false synthesis on the part of the casual reader who otherwise could be deceived into assuming an in vivo affinity not supported by documentation.

Feel free to refer this matter to conflict-resolution. I'm confident that enough other editors will support my position. —Preceding unsigned comment added by Eye.earth (talk • contribs) 01:29, 3 April 2009 (UTC)

The sentence as written is completely clear: AZT has an approximately 100-fold greater affinity for HIV RT as for mammalian enzymes. I know of no reputable source which disputes the fact that AZT is similarly selective in vivo, nor of any that draw the distinctions that you're basing your argument on (though I'm always willing to be educated). MastCell ^Talk 04:28, 3 April 2009 (UTC)

The sentence as written in completely clear with in vitro added. Otherwise it clearly implies an in vivo affinity not supported by any documentation.

"I know of no reliable source . . . " You're arguing from authority. If you know of no reliable source that disputes the in vivo affinity, then to make your assertion you must logically know of reliable sources that afffirm the in vivo affinity. If you didn't, then you'd be guilty of something much worse than the synthesis you and KeepCalm accuse me of. Right? Cite one of those affirming sources, and don't forget "reliable": the building-blocks of proteins are the same, whether for HIV RT or "mammalian enzymes." One of those building blocks is thymine. AZT is designed specifically as a substitute for thymine. That's what it does wherever it encounters an opportunity, and whether it's in a cell or a virus can make absolutely no difference to the analog itself. Eye.earth (talk) 17:49, 3 April 2009 (UTC)

I'm not arguing from authority. I'm arguing from Wikipedia's policies. I do not know of a reliable source which supports your conjecture. I'm asking you to provide one. That's the basis of verifiability. Instead, you're talking in circles. You will notice that I'm not inserting any claims about in vivo behavior for which I lack sources.

As to AZT, you are incorrect: AZT has a much higher affinity for viral RT than for mammalian DNA polymerase, so it will much more readily incorporate into viral nucleic acid. In other words, it does make a difference to AZT whether it's interacting with HIV or a mammalian cell. That's a basic, well-supported biological fact which I have no desire to argue further.

I'm not really interested in enabling your editing behavior, which I find highly inappropriate. If you'd like to have a serious discussion, then I'd suggest abandoning your campaign to force this disputed material into the article over the objections of multiple other editors as a first step. Beyond that, soliciting outside opinions might be useful. MastCell ^Talk 18:33, 3 April 2009 (UTC)

This has gone on long enough. Eye.earth, if you have a reliable source, provide it. If not, ask for comment. You are edit warring against consensus and, as you have admitted, in the interests of a fringe belief you cultivate. This sort of behaviour isn't going to get you anywhere good. Keepcalmandcarryon (talk) 23:25, 3 April 2009 (UTC)

My conjecture? You mean that the affinity is in vitro? My reliable sources are the two footnotes at the end of the sentence referencing two in vitro experiments. The one study specifically asserting a 100-fold affinity in vitro doesn't have in vitro in its title. To be as clear as possible as to what the asserted affinity really is, I inserted in vitro into the sentence.

You are indeed not inserting any claims about in vivo behavior (affinity) for which you apparently do lack sources. Instead, you're deleting a claim of in vitro behavior for which I do have sources -- the two footnotes at the end of the sentence in question. And I wonder about that. Your initial claim that inserting in vitro "belabored" the point seems odd. At worst, the phrase is merely redundant, but most readers are unlikely to know or remember from a chemistry class that all affinity is measured in vitro and that therefore affinity is by definition a strictly in vitro classification. Inserting in vitro is patently not misleading. But deleting it is. I ask readers to consider the statement without in vitro added to it:

"However, AZT has a 100-fold greater affinity for the HIV reverse transcriptase than for the human DNA polymerase alpha, accounting for its selective antiviral activity.[15][17]"

(The two footnotes, again, reference two in vitro experiments.) It sounds like AZT has an unqualified affinity for HIV RT. That's my whole point and that's why I am inserting in vitro into that statement, as follows:

"However, in vitro AZT has a 100-fold greater affinity for the HIV reverse transcriptase than for the human DNA polymerase alpha, accounting for its selective antiviral activity.[15][17]"

And again, for readers just tuning in, the two footnotes reference two in vitro experiments.

You wrote: "As to AZT, you are incorrect: AZT has a much higher affinity for viral RT than for mammalian DNA polymerase, so it will much more readily incorporate into viral nucleic acid . . . That's a basic, well-supported biological fact which I have no desire to argue further."

You actually haven't argued that "biological fact" at all because you refuse to cite a source for it. If you did, you could delete my in vitro edit and insert in vivo in its place. Why don't you do that? Instead, you simply tell me that I should accept your statement at face value. If that's not arguing from authority, what is?

It's not too late to cite a source for in vivo affinity. Lacking such a source, there is no reasonable argument for deleting the phrase in vitro from a sentence that references two in vitro experiments.

The Mode of Action section needs a rewrite anyway. After all, a 100-fold affinity for HIV RT merely assures incorporation of the thymine analog into an infected cell's DNA, resulting in cell death. But exactly the same thing would be accomplished without that affinity because AZT, a thymine analog, was designed specifically to halt DNA replication. RT hadn't even been discovered yet. Surely not even you would argue that AZT's asserted affinity holds outside an infected cell, attracting the AZT like a magnet in order to bypass uninfected cells. Or perhaps you would argue that. If you do, please cite a source. Regardless, AZT's working affinity is towards replicating entities -- whatever they are --- that contain thymine. Once assimilated the entity dies. Eye.earth (talk) 21:05, 6 April 2009 (UTC)

MastCell is the one who needs to cite a reliable source. My reliable sources are the two footnotes at the end of the disputed statement. As for the rest, I've opened an RfC.Eye.earth (talk) 21:05, 6 April 2009 (UTC)

Again, I have no desire to argue about how AZT works with you, particularly since you are repeating somewhat idiosyncratic arguments most common to AIDS-denialist websites and thus seem unlikely to seriously consider the mainstream scientific understanding of AZT. I'll await input from your request for comment rather than repeating myself on why in vitro is redundant and/or misleading here. MastCell ^Talk 00:02, 7 April 2009 (UTC)

Again, you haven't argued it at all. But I'll wait for comment, for now. You're right that I am unlikely to seriously consider the mainstream scientific understanding of AZT, a chemotherapeutic drug now presented as a "smart" virus fighter, homing in on HIV RT. But you might explain to new readers, led here by the RfC, how AZT's implied in vivo virus-centric affinity makes any difference. Affinity or not, the cell dies. The asserted affinity (described specifically as in vitro in the two footnotes at the end of the disputed sentence) doesn't rule out the mass death of uninfected replicating cells. It's not as if AZT's original function as a thymine substitute for cellular DNA fails when it can't find enough HIV RT to keep it occupied. As I say, you might explain this to any new readers, presumably more likely to seriously consider the mainstream scientific understanding of AZT. But it's my impression that the mainstream scientific understanding of AZT was established when it was synthesized, in 1964. —Preceding unsigned comment added by Eye.earth (talk • contribs) 16:43, 7 April 2009 (UTC)

OK. AZT is a thymine analogue. It competes with thymine nucleosides for incorporation into DNA, and if incorporated it will terminate DNA synthesis. AZT has a strong molecular attraction to HIV reverse transcriptase, and a poorer attraction to human DNA polymerase. Therefore, AZT can inhibit viral DNA synthesis at low concentrations (~ 0.005 micromolar), while much higher concentrations (~ 100-230 micromolar) are required to inhibit human DNA synthesis. Thus, if AZT is present in concentrations somewhere between those two numbers, it will inhibit HIV DNA synthesis without inhibiting human DNA synthesis. That's called a therapeutic window, a basic concept in pharmacology. (The numbers I've cited are approximations as I don't have the data right in front of me, but can be confirmed with reference to, for example, PMID 2671731).

Obviously, there are complicating factors: human mitochondrial DNA synthesis is sensitive to AZT, accounting for some of its toxicity, and bioavailability and pharmcokinetics complicate the seemingly straightfoward goal of obtaining a therapeutic tissue level. But I don't really understand your rhetoric, which seems highly anthropomorphised. Sure, AZT is "smart" in the sense that it's fairly selective - virtually any antimicrobial drug in existence is similarly "smart", but your usage implies skepticism, as if this were somehow suspect or exceptional. Yes, AZT was originally developed as an anticancer drug - again, it's quite common for drugs developed for one indication to prove more useful for another - witness thalidomide as a treatment for multiple myeloma, or amantadine for Parkinson disease, or MAO inhibitors, etc etc. You're again suggesting there's something odd about this, which I assume is just a lack of familiarity with the relevant basic concepts.

I don't expect to convince someone who's capable of denying the existence of AIDS and asserting that HIV is harmless, but perhaps, as you say, others will find that elaboration useful. MastCell ^Talk 21:17, 7 April 2009 (UTC)

Bravo. So why are you removing my in vitro edit from a sentence referencing two in vitro experiments?

". . . and if incorporated [AZT] will terminate DNA synthesis." You mean when incorporated. Not if. When a cell replicates, it has to copy thousands of times more DNA than the tiny amount in a virus. That's thousands of times more natural thymine for an analog to replace. And that's not even counting the mitochondrial DNA, which even you admit is sensitive to AZT. Even the presence of thymine analogs within the in vitro therapeutic window you describe (and the size of which is disputed, to say the least) won't stop at least one of them from being incorporated into a cellular DNA chain in vivo, killing the cell. Your implied in vivo affinity is swamped by a larger opportunity.

In light of the above, please explain the therapeutic value of any AZT in vivo affinity for HIV RT. If the analog is incorporated into HIV's DNA by the virus' RT, then wouldn't that defective chain then be incorporated into cellular DNA, killing it during replication anyway? What's the difference if the cell is killed directly by the analog (as it was designed to do) or indirectly via viral DNA? On the other hand, if the defective viral DNA isn't incorporated into cellular DNA, is that going to stop another analog from stopping cellular DNA synthesis directly, again as it was designed to do?

The link you provided doesn't lead to the article itself, but the numbers you cite, lacking any references, must be assumed as being derived from in vitro experiments. Which means that your therapeutic window is in vitro. In vitro experiments use live viruses. But in asymptomatic HIV+ patients the virus is dormant, as it can also be in symptomatic Aids patients (indeed it's possible to be an at-all-appearances classic Aids patient without HIV at all). The virus isn't actively replicating as an infectious entity in those people. The body has suppressed it (thus the antibodies to HIV in the first place) as it suppresses the myriad potentially harmful parasites, bacteria, and other viruses that can and do inhabit a healthy human body. So there is no RT for AZT to be attracted to, is there? And even in patients with an active infection in progress, the number of infected cells is a small fraction of the uninfected ones. So that leaves an awful lot of uninfected cellular DNA at the mercy of the thymine analog called AZT.

Regarding "smart". I'm aware that antimicrobial drugs can be "smart" -- because they are designed to be smart. AZT wasn't so designed, but I know that drugs invented for one purpose often work better for some unintended purpose. But efficacy at an unintended purpose doesn't change its efficacy or lack thereof for its original purpose. AZT's original function is chemotherapeutic. An in vivo affinity for HIV RT doesn't change that and doesn't even hinder it in any serious way.

Aids denialists don't deny the existence of Aids. We deny the importance of HIV as the cause of Aids. Readers, if any! Are you beginning to see why?

Again, why remove my in vitro edit from a sentence referencing two in vitro experiments? You've never really answered that question. —Preceding unsigned comment added by Eye.earth (talk • contribs) 00:43, 8 April 2009 (UTC)

There is no need for "in vitro" in this context - that's inherent in enzyme affinity measurement, and does not clarify the point being made. This enzyme affinity has been measured using widely-accepted methods. By the way, regarding the comment a few paragraphs above this one, it is very clear that HIV is not dormant in asymptomatic HIV+ persons; rather, it's been convincingly demonstrated over and over since 1995 that the replication rate of HIV is quite high except in the context of combination antiretroviral therapy. --Scray (talk) 03:03, 8 April 2009 (UTC)

". . . does not clarify the point being made." What exactly is the point being made then? If it's that the affinity is in vitro, it surely does no harm to emphasize that fact to casual readers unfamiliar with the clinical meaning of "affinity". You couldn't call it contradictory to do so. On the other hand, if the point is to imply an in vivo affinity, why imply when you can come right out and say it -- with sources, of course. My sources are the two footnotes at the end of the sentence -- two in vitro experiments.

"This enzyme affinity has been measured using widely-accepted methods." Sure it has -- using widely-accepted methods with active viruses in vitro.

". . . replication rate of HIV is quite high . . ." Please explain how a "quite high" viral replication-rate could persist without any symptoms of infection for the latent interval period of -- what is it now, ten or twenty years? A bout of flu-like symptoms is a common report after initial HIV infection, after which the virus is suppressed by antibodies. Just like any other virus. Eye.earth (talk) 05:48, 8 April 2009 (UTC)

The affinity of HIV RT for zidovudine has been determined using standard methods for measuring affinity; this approach is widely-accepted, so it can simply be described as "affinity" without "in vitro". In response to your direct questions, it is clear that a virus can replicate at high levels during chronic infection in a human without causing symptoms (TTV, GBV-C, and HBV are just a few examples]]). It is also clear that anti-HIV antibodies generally fail to suppress replication (as is also the case with hepatitis C virus, among others); however, this is drawing the discussion off-topic. There is no need for addition of "in vitro" to standard measures of enzyme affinity assays. --Scray (talk) 12:11, 8 April 2009 (UTC)

Do we have an article on the affinity assays in general? I don't see one, but I'd be surprised if it isn't out there somewhere. Wikilinking that would be a much better to deal with the issue than cluttering this article with qualifiers that don't add much to the reader's understanding of the topic. People who want to know more about the methodology could follow through there, explaining how those tests work here seems inadvisable. SDY (talk) 22:00, 8 April 2009 (UTC)

Dissociation constant#Protein-Ligand binding is the closest I've found. Affinity is a disambiguation which mentions the pharmacologic/biochemical usage, but it might be worth at least a stub on the topic. MastCell ^Talk 22:51, 8 April 2009 (UTC)

Just a quick note to say I support what MastCell and Scray have said. Keepcalmandcarryon (talk) 17:48, 10 April 2009 (UTC)

"The affinity of HIV RT for zidovudine has been determined using standard methods for measuring affinity." Sure, in vitro using live viruses. The use of the word "affinity" doesn't necessarily imply or specifically refer to an in vitro environment by default. The use of the word "affinity" means exactly what Webster's says it means: "an attractive force between substances or particles that causes them to enter into and remain in chemical combination." The matter of how it was measured is unstated. It describes what exists. Affinity may indeed always be measured in vitro. But due to the nature of the disputed statement, the question is whether an affinity measured in vitro can be implied without comment or clarification to exist in vivo. Consider again the sentence in question: "However, AZT has a 100-fold greater affinity for the HIV reverse transcriptase than for the human DNA polymerase alpha, accounting for its selective antiviral activity." That sure sounds like in vivo to me.

"Wikilinking that would be a much better to deal with the issue than cluttering this article with qualifiers that don't add much to the reader's understanding of the topic." At least SDY is admitting that there are going to be readers out there who will need further understanding. But adding in vitro doesn't clutter anything. Indeed, adding a Wikilink would add clutter by sending the reader away from the page in search of information that could be perfectly summarized by the phrase in vitro. Again, the whole point of adding in vitro is simply to refer to the two in vitro footnotes at the end of the sentence.

"People who want to know more about the methodology could follow through there . . ." The whole point of my insert of the phrase in vitro is that casual readers aren't necessarily going to know that "affinity" refers to a specific methodology at all. They're going to attribute to it nothing more than its dictionary definition.

Regarding the three viruses with allegedly high yet asymptomatic rates of viral reproduction, TTV,GBV-C, and HBV. According to their respective articles, neither TTV nor GBV-C are known to cause disease, and in the former example its reported exposure is 100% in some areas. If they were truly replicating at a high rate, they would eventually cause problems. Those problems would eventually manifest themselves as symptoms to the infected individual. But they don't cause problems, at least none discovered yet. As for HBV, "More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus." Presumably those are the people who weren't vaccinated. Both sets of people would of course have antibodies to the virus, like people infected by HIV. Also, I notice that HepB doesn't have a stipulated latent period like HIV is said to have. Basically, you can get HepB, never show symptoms, and eventually die later of anything else. Also like HIV. I thought this was good: "Patients who undergo chemotherapy are at risk for HBV reactivation. The current views are that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver." AZT, of course, is chemotherapy.

All this talk over my adding in vitro to the following sentence: "However, in vitro AZT has a 100-fold greater affinity for the HIV reverse transcriptase than for the human DNA polymerase alpha, accounting for its selective antiviral activity.[15][17]" (And once again, the two footnotes refer to in vitro experiments.) So according to various editors this phrase is misleading, unnecessary, and adds clutter. Actually, it's clarifying, essential, and concise. —Preceding unsigned comment added by Eye.earth (talk • contribs) 14:45, 11 April 2009 (UTC)

I think the concern is that saying it that way implies there's a difference between in vitro and in vivo activity and that other editors believe that this is misleading since there is no evidence of a substantial difference, and the technique in question is widely used with the assumption that there is no substantial difference. As the old yarn goes "do not write to be understood, write so that you cannot be misunderstood" and this is something that could be misunderstood. SDY (talk) 17:10, 11 April 2009 (UTC)

Perhaps my latest edit will not be misunderstood. —Preceding unsigned comment added by Eye.earth (talk • contribs) 01:35, 12 April 2009 (UTC)

"In vitro", continued

Enough nonsense. If you aren't willing to listen to the feedback which you yourself solicited - all of which has deemed this edit unecessary and potentially misleading - then I think we're done here. MastCell ^Talk 03:00, 12 April 2009 (UTC)

I concur - consensus is clear. --Scray (talk) 03:17, 12 April 2009 (UTC)

“Enough nonsense.” As if all the previous points I’ve made, none of which you have successfully refuted head on, can be dismissed like that. A persistent lack of integrity shines like Rudolf’s nose. As for the feedback, the RfC isn’t closed yet. Feel free to pursue arbitration. I’d love to see your presentation of the dispute.

“The consensus is clear”: Consensus means general agreement. Mere numerical majority doesn’t create it. You have to convince, refute, educate the opposition. You’ll never do that until you cite a good source backing your position. That position seems to be represented by SDY’s comment above, namely, that the real issue is in vivo affinity. If so, why revert my last edit? It comes right out and states an ‘’in vivo’’ affinity, and then leaves the door open for anyone to cite a reliable source. Can’t even one of you come up with a reliable source addressing the issue of a therapeutic in vivo affinity? The distinction between in vivo and in vitro is surely one of the most fundamental tenets of medical science. It will have to be addressed, not taken for granted like it was before this dispute began.

I’m going to try another compromise and stick with it for awhile. But eventually a source will have to be cited or I'll go back to my original in vitro edit. —Preceding unsigned comment added by Eye.earth (talk • contribs) 19:24, 12 April 2009 (UTC)

This "compromise" is just more of the same as above, and is unnecessary. Binding affinities are measured in vitro as a standard approach. Asking for a citation for this in this article would be a distraction - perhaps you'll want to take that up on the Talk page for the page cited previously (a few paragraphs up) for binding affinity. --Scray (talk) 20:32, 12 April 2009 (UTC)

Just as a global FYI, given the lengthy and unrewarding experience of interacting with Eye.earth on these topics, I've posted the situation at WP:AN/I for feedback. This is well beyond the point of WP:IDIDNTHEARTHAT. MastCell ^Talk 04:30, 13 April 2009 (UTC)

Eye.earth, the time has come for you to choose your course of action. You must have noticed that the article does not contain your preferred form of words. Continued repetition of your arguments here is not going to change that, and continued block evasion on your part is going to be counter-productive. Avenues open to you include (1) accepting that consensus is against you and that you are unlikely to convince anyone here that your preferred content is best, or (2) using our dispute resolution guidelines to seek input from further editors. SHEFFIELDSTEEL^TALK 19:37, 15 April 2009 (UTC)

Responding to the request for comment: I completely agree with Mast-Cell on this one. While it is true the information is from in vitro studies, this is a distinction without a difference. You might as well note that these measurements were all collected during solar flares or odd numbered Tuesdays. It simply doesn't matter that they are in vitro measurements unless there is an identifiable bias in these measurements. As an aside, is there any way to get access to my account which I never set up an email address for, and the pass-word of which I have forgotten ;) Matthew S. Ackerman —Preceding unsigned comment added by 75.13.227.135 (talk) 17:43, 21 April 2009 (UTC)

"...this is a distinction without a difference..." I'm afraid there is a difference. In vitro uses an abundance of live viruses in a concentration that simply can't be found in a human body, even in cases of active infection. But most people who score positive on an HIV test simply have antibodies. The virus itself is dormant. Anyway, the affinity isn't therapeutic for long, contrary to what the sentence dishonestly implies without my in vitro edit: see the paragraph entitled Viral resistance.

"You might as well note that these measurements were all collected during solar flares or odd numbered Tuesdays." Let's suppose there existed a tradition of using, in scientific-literature, specific phrases in Latin for periods of solar-flares, and odd-numbered Tuesdays. And the measurements were collected during solar flares or on odd-numbered Tuesdays. However, one of the footnote references detailing the measurements taken during solar-flares or on odd-numbered Tuesdays failed to contain the appropriate Latin phrase in its title or abstract. It would hardly be deceptive of someone to insert that phrase into the sentence. Right?

But suppose you wanted to imply that the measurements weren't taken during solar flares or on odd-numbered Tuesdays. Removing the phrase would be the way to do that, wouldn't it? Eye.earth (talk) 03:34, 23 April 2009 (UTC)

Your first statement is factually incorrect - the vast majority of people who are positive for anti-HIV antibodies also have evidence of the virus in their blood. I think it is important to note that raising this point (the one I am refuting) in this context underscores the link between this discussion and AIDS denialism. --Scray (talk) 04:13, 23 April 2009 (UTC)

If you believe the concentration of viruses in vivo makes the affinity therapeutic, why don't you insert the phrase in vivo into the disputed sentence -- and then cite a study justifying your edit? Could it be that the study doesn't exist because the concentration necessary can't possibly exist in vivo? And so you are reduced to dishonestly implying an in vivo affinity by deleting the phrase in vitro from a sentence referencing two in vitro experiments?

In opposition to the catch-all demonizing phrase "Aids denialist", I propose the phrase "pharmasock". A pharmasock is someone who uses Wikipedia to advance positions that can only be explained by that person deriving financial sustenance from the HIV/AIDS academic-governmental-pharmaceutical complex. —Preceding unsigned comment added by Eye.earth (talk • contribs) 18:43, 23 April 2009 (UTC)

Look Eye.earth by now it should be abundantly clear to you that literally no one agrees with you. You are resorting to paranoid-conspiracy theories to explain this disagreement, which should be a major red flag for you. Seriously, I have absolutely no dog in this fight. But, I would honestly really like to convince you that the science is sound, because I like you. However, wikipeidia talk pages are not the place to have long debates about the validity of a point. The consensus is clear, and if you wish to have a discussion about the science in another forum, I would love to, but it is time for you to move on. Matthew Ackerman (talk) 12:59, 24 April 2009 (UTC)

Now you say that "the science is sound." Exactly what science are you referring to? Remember, the whole issue here is nothing more nor less than my attempt to insert in vitro into a sentence referencing two in vitro studies. The study explicitly claiming a 100-fold affinity doesn't happen to contain the phrase in vitro in its title or abstract (it's found in the text where you would expect to find it, as in: "The thymidine analog 3'-azido-3'-deoxythymidine is a potent inhibitor of HIV replication in vitro . . . "). Inserting in vitro into the disputed sentence makes specific for casual readers the fundamental nature of the asserted 100-fold affinity. That's it. It isn't deceptive. It's not bad science. To the contrary, its deceptive and bad science to leave the phrase out, because doing so implies to casual readers a therapeutic in vivo affinity not supported by the references.

You say that "wikipeidia talk pages are not the place to have long debates about the validity of a point." They aren't? I really would have thought that they were. If not here, where? It's not as if space is rationed. And anyway, there's a simple way to end this discussion right here: stop responding to my comments.

With that hopeful prospect in mind, I will summarize the dispute:

I inserted the phrase in vitro into the following sentence: "However, in vitro AZT has a 100-fold greater affinity for the HIV reverse transcriptase than for the human DNA polymerase alpha, accounting for its selective antiviral activity.[16][18]"

The two footnotes reference two in vitro experiments. The conclusions drawn from them are necessarily in vitro. But one of them lacks the phrase in vitro in its title. Adding in vitro to the sentence simply ensures that casual readers will not mistakenly assume a therapeutic in vivo affinity not supported or asserted by the references. That's it! That's the whole dispute.

I encourage you to pursue arbitration if you find this outcome unsatisfactory. In your presentation of the dispute, don't forget to use the phrase "Aids denialist propaganda" when describing my "paranoid-conspiracy theories." —Preceding unsigned comment added by Eye.earth (talk • contribs) 17:18, 24 April 2009 (UTC)

MacMed^talk_stalk 02:53, 19 June 2009 (UTC)

I had actually started an RFC earlier but it evidently expired from lack of interest too.

Let it be noted as well that "AZT was credited with saving over 50,000 years of life for AIDS sufferers between 1994 and 1999 in the USA" is down the memory hole. Its persistent tag was a neon example of auto-reversion. Not to worry. Its replacement, . . . "significantly altered the course of the illness" is doublespeak worthy of George Orwell or John Cleese. Eye.earth (talk) 21:58, 9 July 2009 (UTC)

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