Talk:Zidovudine/Archive 1

Confusion
Attention: I'm a bit confused about the following paragraph in the article: "When used as a preventative treatment, AZT has proven to be particularly effective. If treatment is started before the total amount of virus, known as the viral load, reaches a critical point of 50 million parts per millilitre of blood serum, the chance of AIDS developing is effectively zero. This is widely used with medical practitioners who receive accidental infections."

Aren't two things being confused here? I'm not a doctor, but from what I've heard, antivirals given shortly after exposure (preferably within a few hours) to HIV virus can decrease the risk of becoming infected by about 80%. If succesful, the person would test negative on HIV tests. This treatment type is known as PEP. However, the article talks about treatment starting af 80 million copies/mL and claims this will decrease risk of getting full-blown AIDS to 0%. 80 million copies/mL seems like a fairly high number so I doubt that it can be PEP the paragraph is referring to (additionally, PEP doesn't decrease the risk to 0%). Rather, it seems the article is talking about the possibility that therapy initiation in the first weeks/months after infection (ususally when symptoms of acute HIV develops) will lower the viral set-point and improve long-term prognosis even after treatment is stopped (in this scenario the patient would still test positive on HIV tests). However, from what I've read, this is currently being researched and there's no solid evidence of this. So how could the risk be practically 0% as the paragraph claims? The best we can say that it delays onset by, say, 15 years because that is the longset people receiving early treatment has lived until now.

AIDS was actually considerably more widespread in Africa is rather presumptive. The criteria for labelling a case "AIDS" are much weaker (broader) in Africa than they are in North America. And it was not suggested AZT was the cause of AIDS, but a cause, under the substance-abuse rubric. Malnutrition and starvation -- long a problem in Africa, worse after "First World" and IMF resource stripping -- can also resemble the AID syndrome, and doubtless compound the effects of pollutants. -- Kwantus

Do they actually still prescribe this poison? I thought the 1993 Concorde study -- one of the only ones not funded by the manufacturers -- put an end to it when it showed AZT had a statistically higher death rate than placebo. 142.177.24.141 03:46, 27 Jul 2004 (UTC)
 * Yes, it's still being used, but nowadays usually not as monotherapy, and in smaller doses than in the Concorde study. The main finding of the Concorde study was, that they could find no benefit in taking the drug before the symptoms appear, ie. the progression to advanced disease wasn't affected.

I wouldn't call the difference in death rate (176/171) statistically higher (bad luck?). After all that was just one study, there are others that contradict. Here's a couple of sites on AZT safety: a WHO study, NIAID site and AEGiS. Daevatgl 18:22, Jul 27, 2004 (UTC)

Not sure how to post here... but AZT is the phased out name for ZDV, why not call it that? Sophronesis (talk) 11:13, 7 October 2008 (UTC)

In accordance with WikiProject_Drugs naming policy, I propose we move this page to the INN zidovudine. If you have any concern with this proposal, please discuss it on this page. Matt 18:09, 23 Dec 2004 (UTC)

Patent issues section
That the Greg Palast book is cited in this article at all is reason enough to question its accuracy. First of all, the lawsuit to which the section presumably refers may have been aided by Public Citizen, but the actual title was Burroughs Wellcome Co. v. Barr Labs., Inc.,. Secondly, the line about the taxpayer footing the entire bill for the drug development is probably nonsense -- I assume that BW paid for the clinical trials (which are another massively expensive part of drug development) and the chemical engineering needed to scale up production (yet another oft-overlooked part). Since the case isn't online, I'll have to check back before changing anything. But it is cited in a few opinions that are online: search this opinion for 'AZT' to find one. jdb &#x274b; (talk) 06:45, 26 Mar 2005 (UTC)

Hungarian word "azt"
I cut this recent anonymous addition from the article, as it seems unlikely that an English-language encyclopedia would need an entry on the Hungarian word for "that":
 * Azt also means 'that' in Hungarian.

If an Englsh-language entry is desired for that word, it may be better to put it at azt instead. There is no entry in [hu.wiktionary.org The Hungarian Wiktionary] for it, though, and I don't speak Hungarian, so I'll let someone else write azt and azt if they're important. The Rod 21:21, 9 January 2006 (UTC)

Martinez reference
I've cut the reference to this paper by M. Martinez. You can dispute anything you want if you cite Medical Hypotheses, which is not a peer reviewed journal. In any case the article is out of date. Trezatium 19:52, 5 April 2006 (UTC)


 * Just a quick reply I don't want to get into a debate. Medical Hypotheses isn't peer reviewed, but there are occassionally some good articles there. This particular citation is a good paper, and still valid despite being several years old. The article discusses the genetics of mutation and drug resistance as it relates to nucleoside analogs. These genetics don't change through the years, so still valid. The article points out a lack of laboratory evidence for drug resistance by nucleoside analog drugs. For example, lack of correlation between reverse transcriptase activity and drug resistance. Keep in mind the standard AIDS articles from the peer reviewed journals from the 1980s are still cited.mwtzz 15 June 2006


 * I'm afraid I don't have access to the full text of the article, but the abstract claims that, "laboratory techniques which test for viral sensitivity to the drugs fail to provide direct evidence for the existence of [drug resistance]." More recent studies of phenotypic and genotypic resistance tests appear to contradict this claim. Trezatium 18:54, 15 June 2006 (UTC)


 * Yeah but putting the cart before the horse isn't good science and puts into doubt the original theory. In other words, claiming HIV develops drug resistance, then providing the evidence years later ... mwtzz


 * What matters here is the current state of knowledge, not when that knowledge was acquired. Evidence of NRTI resistance is abundant. Trezatium 19:29, 15 June 2006 (UTC)

Does anyone have a bottle of AZT? I have read on a wiki talk page that AZT's included pamphlet gives a list of warnings - one of which is AIDS like symptoms. Worth a picture or link or confirmation. Duesberg may already have this on his site - funny how long it takes anyone to bother to read one of those warning blurbs.159.105.80.141 19:45, 25 May 2007 (UTC)

My understanding - maybe incorrect but in the literature as they say - is that AZT is known to harm/kill the immune system. How could you tell if it was AZT or HIV or if HIV was just around for the ride? Taking a drug that kills your immune system sounds like a chaser when you are already drunk(ie not likely to help much).159.105.80.141 20:00, 25 May 2007 (UTC)


 * Read the Wikipedia articles on AIDS reappraisal and follow some of the source links there. Short answer - AZT doesn't cause AIDS. MastCell Talk 19:12, 26 May 2007 (UTC)


 * That's a rather deceptive response considering that the definition of AIDS includes a "positive result on an HIV antibody test". Pneumonia + HIV negative = Pneumonia.  Pneumonia + HIV positive = AIDS.  A more useful question would be, to what degree do the unwanted side effects of AZT mirror the symptoms of AIDS? Loundry 18:21, 5 November 2007 (UTC)

My understanding from the "reappraisal" article and others is that AZT was a shot in the dark that doesn't seem to cure AIDS either. It seems that destroying the immune system would have little benefit to someone with a weaken immune system - but then Duesberg seems to rely on logic. Is AZT still used or has it been replace/supplanted?159.105.80.141 11:20, 29 May 2007 (UTC)


 * Read the Wikipedia articles on HIV and AIDS, specifically the section on treatment. MastCell Talk 19:26, 29 May 2007 (UTC)

Interesting articles - it used to be too deadly but all they had. Now they give a smaller dose combined with other stuff ( all made by Glaxco it seemed ). They mentioned using vitamis and mineral supplements and small dose of poison - sounds like homeopathy ( very similar to the witnesses that were not allowed to testify in the S African AIDS trial - Andre Pan*** ). 159.105.80.141 16:31, 30 May 2007 (UTC)

Skull and bones label debate
Besides the AIDS warning in the included pamphlet there also seems to be a skull and crossbones on the outside label - not a reassuring symbol on a medicine bottle.159.105.80.141 16:33, 30 May 2007 (UTC)


 * This is because AZT has an FDA "black box" label. If my understanding is correct, a "black box" label is given to a drug if it has caused permanent damage or death during regular use.  I think this information should be included in the article. Loundry 18:21, 5 November 2007 (UTC)


 * Not exactly. A "black box warning" (more accurately, a boxed warning) is used by the FDA for a variety of reasons, including to highlight potentially serious or important side effects, to draw attention to important monitoring requirements, or to communicate any information deemed of great importance to a prescriber. A fairly large number of widely used medications carry black box warnings (for example, the anticoagulant warfarin). Given the level of, to put it kindly, uninformed commentary (for instance, there is no skull and crossbones on any package insert in the US, much less on that of AZT), I'd prefer that we're very scrupulous about how we present a boxed warning and what context we give. MastCell Talk 22:20, 5 November 2007 (UTC)


 * Thank you for the information. According to the site you listed, a black box warning is issued when one of the following happens: * There is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life-threatening or permanently disabling adverse reaction) that it is essential that it be considered in assessing the risks and benefits of using a drug OR * There is a serious adverse reaction that can be prevented or reduced in frequency or severity by appropriate use of the drug (e.g., patient selection, careful monitoring, avoiding certain concomitant therapy, addition of another drug or managing patients in a specific manner, avoiding use in a specific clinical situation) OR * FDA approved the drug with restrictions to assure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted (e.g., under 21 CFR part 314, subpart H, § 314.520 “Approval with restrictions to assure safe use”).  In the case of AZT, which of the three listed reasons caused it to be given a black box warning?  I think this information should be included in the article, ESPECIALLY if it is the first of the three cases (namely, "a fatal, life-threatening or permanently disabling adverse reaction").  I also reject your "helpful correction" with the sanitized "boxed warning" term considering that both black box warning and black box label are commonly-used terms to warn against the demonstrated harm done by regular usage of prescription drugs. Loundry (talk) 22:54, 20 November 2007 (UTC)


 * The side effects of AZT are covered in this article. If you feel they should be covered differently, then please propose alternate wording with appropriate reliable sources. My point above (beyond a relatively pedantic one about proper terminology) was that you seem to placing quite a bit of weight on the boxed warning; in fact, many commonly used medications bear boxed warnings and are used effectively with a good risk/benefit ratio. Rather than saying "OMG it has a black box!" we should be accurately and neutrally presenting what's known about this medication's side effects. MastCell Talk 23:05, 20 November 2007 (UTC)

Regarding MastCell’s statement above that “there is no skull and crossbones on any package insert in the US, much less on that of AZT”, follow this link:

http://images.google.com/images?hl=en&q=AZT+label&gbv=2

Loundry: you needn't "propose alternate wording" to MastCell nor anyone else. Wikipedia encourages bold editing. Eye.earth 21:44, 3 December 2007 (UTC)
 * Yes. Wikipedia also encourages the insertion only of information verifiable in a reliable source (though that's more often overlooked than WP:BOLD). Google image searches are not a reliable source. MastCell Talk 16:54, 4 December 2007 (UTC)
 * Erm—excuse me, but that's a label of research-grade AZT (apparently from Sigma-Aldrich). It is not a package insert, and it is not a drug label. The toxicity described on the label (blood and bone marrow, i.e. bone marrow suppression) is indeed a side effect of AZT, and is mentioned in the article. Fvasconcellos (t·c) 22:20, 3 December 2007 (UTC)
 * Erm-exucse me, you IDIOT, the AMOUNT of AZT in the research-grade AZT container is LESS than that prescribed in medication dosages. How can "X" amount of "research grade" AZT warrant a cross bones label, when 25 times the "X" amount in prescription is just a "package insert"??? 69.44.242.118 04:44, 4 December 2007 (UTC)
 * Calm down, take a deep breath, and try to avoid personal attacks (you'll be taken more seriously). The issue is, of course, not the relative amounts of the drug. Research-grade chemicals are not intended for human use and have not met the rigorous standards expected of pharmaceutical formulations. I feel fairly confident, from my days in the lab, that if you found a bottle of research-grade ethanol it would have a skull and crossbones on it. Yet the bottle of Tanqueray in my liquor cabinet doesn't have a skull and crossbones. Again, no pharmaceutical product is labeled with a skull and crossbones, citing Google images is hardly going to convince anyone of your correctness, and the whole skull-and-crossbones thing is an AIDS-denialist canard which thrives on misinformation. MastCell Talk 16:52, 4 December 2007 (UTC)
 * MastCell, how is "research-grade" AZT any different in chemical composition from "pharmaceutical" AZT?? Both are chemically and physically identical. AZT must be synthesized in the laboratory, it is not a naturally occurring substance. If I held one bottle of "research-grade" AZT in one hand, one bottle of the same amount of "pharmaceutical" AZT in the other, then mixed them up behind my back and asked you to tell which was which, how would you tell?? YOU CAN'T. Your canard about research-grade chemicals not being "intended for human use" because they have not "met the rigorous standards expected of pharmaceutical formulations" leaves me flabbergasted. If you read the research-grade AZT label, the reasons justifying the toxicity claims are spelled in plain English, and they have absolutely nothing to do with "rigorous standards expected of pharmaceutical formulations" they have to do with the direct biochemical consequences of ingesting AZT. And yes, the issue *IS* the relative amounts of the drugs. Water is toxic at a high enough dosage. So, there is no way to tell "research-grade" AZT from "pharmaceutical" AZT, they are chemically indistinguishable, the research label has a skull and crossbones, advising you to seek "medical help" if you happen to ingest the ENTIRE bottle's contents, yet if you are an HIV patient and happen to ingest 10 times that amount each and every day of your life, for the rest of your life, you are not in NEED of "medical help" you are FOLLOWING "medical help". Black is white. Left is right. Up is down. Unbelievable. 69.44.242.118 (talk) 00:46, 5 December 2007 (UTC)


 * I'm not very interested in continuing this argument. You do understand the idea of a risk-benefit ratio? That cisplatin, for instance, is "poisonous" - it makes you vomit and lose your hair, it can easily kill you, and if it's lying around a laboratory in a bottle it should definitely have a skull and crossbones on it? But that if you have testicular cancer, it will save your life if used judiciously? These are not particularly sophisticated concepts. MastCell Talk 01:39, 5 December 2007 (UTC)

Readers: notice that MastCell:

1) failed to explain why Google images are inherently different from any other images that appear in Wikipedia;

2) implied they are unsuitable even for the discussion page;

3) concluded from them that “ . . . no pharmaceutical product is labeled with a skull and crossbones” !

4) advised one commenter to "Calm down, take a deep breath, and try to avoid personal attacks (you'll be taken more seriously)."

5) then wrote: “the whole skull-and-crossbones thing is an AIDS-denialist canard which thrives on misinformation.”

Eye.earth (talk) 00:47, 9 January 2008 (UTC)


 * This page is not a discussion forum. If you seriously believe that Google Images is a reliable source, then I invite you to ask for a third opinion or take it to the reliable sources noticeboard for more input. Otherwise, please step down from your soapbox and take the grandstanding elsewhere. MastCell Talk 02:09, 9 January 2008 (UTC)

6) presumed I was the poster (IP address 69.44.242.118, above), who called Fvasconcellos an idiot (see User_talk:Eye.earth, 4th paragraph).

Eye.earth (talk) 00:47, 30 January 2008 (UTC)


 * M'kay. Anything else that might actually be useful for the article? The side effects of AZT are covered. If you'd like to propose alternate wording, drawing from reliable sources, then please do so. MastCell Talk 04:55, 30 January 2008 (UTC)


 * The AZT label with the skull and bones, in the personal webpage of a National Academy of Science member . Is this source good enough, sir? Randroide (talk) 17:25, 26 April 2008 (UTC)


 * Looks to me like a label for a laboratory chemical (i.e. not the label on the pharmaceutical). The fact that AZT is toxic is not under debate (and is presumably discussed by the prescribing physician), only the appearance of the label and associated materials sent to patients. There are different labeling requirements for the same chemicals depending on intended use. I can confirm MastCell's recollection above for at least my lab - the ethanol is labeled as poisonous and flammable, and everyone expected to be using it is required to read the MSDS.
 * Further, Deusberg is pretty iffy as a reliable source. - Eldereft ~(s)talk~ 19:43, 26 April 2008 (UTC)


 * Of course is a bottle of AZT intended for laboratory use. That´s just Duesberg´s point.


 * Could you please tell me why Peter Duesberg is iffy as a reliable source?. Please take a look at his cualifications. Randroide (talk) 20:17, 26 April 2008 (UTC)
 * His qualifications on HIV/AIDS? He's conducted no research on the virus, and his views on it are universally considered wrong-headed and incorrect by the scientific community. This is a non-starter, for the reasons that have been discussed ad nauseum above. Bottom line: this page is not a platform for AIDS denialism. Duesberg's views on HIV/AIDS are those of an extreme minority; they are given well more than their due weight at AIDS reappraisal, but the effort to metastasize a fringe AIDS-denialist viewpoint to all vaguely related articles is fundamentally at odds with the basic policies and purpose of Wikipedia, which is to accurately summarize the current state of human knowledge and to provide overviews of scientific topics which are in line with respected scientific thought. You're welcome to seek outside input on this, but the skull-and-crossbones thing is a fairly obvious attempt to play on ignorance and, more importantly, not appropriate for this article. MastCell Talk 22:01, 26 April 2008 (UTC)

History Section
I've removed the reference to Marty St. Clair's involvement in the discovery of AZT's effectiveness on HIV as I find it hard to believe that for over 20 years nobody said a word. Further research has shown that her name appears very sparingly with AZT while the other researchers have numerous references. Finally, I'm in the process of Reading The Truth About Drug Companies by Marcia Angell and I will take the word of the former Editor of The New England Journal of Medicine over a BBC article posted less than three months ago.75.111.51.215 (talk) 08:54, 13 February 2008 (UTC)

Fallout between government/Duke scientists and Burroughs Wellcome.
Please edit the page to reflect the conflict between the pharm company and government/Duke researchers. This article does a great job to leave out the issues between them which is unfortunate because readers might assume that Burroughs Wellcome actually contributed significatnly to the inception and discovery of its use for AIDS treatment.

to quote from a letter to the NYtimes in 1989 by some of those researchers "Indeed, one of the key obstacles to the development of AZT was that Burroughs Wellcome did not work with live AIDS virus nor wish to receive samples from AIDS patients."

"- The company did not conceive or provide the first demonstration of an effect against animal retroviruses. This  was done by Wolfram Ostertag at the Max Planck Institute in  1974, using a mouse retrovirus in a test tube. Mr. Haigler's  implication that his staff  discovered" the antiretroviral potential of AZT in 1984 is noteworthy. What he did not say was that his staff repeated the Ostertag mouse experiments. You cannot discover" something published by someone else 10  years earlier.

- The company specifically did not develop or provide the first application of the technology for determining whether a drug like AZT can suppress live AIDS virus in human cells, nor did it develop the technology to determine at what concentration such an effect might be achieved in humans. Moreover, it was not first to administer AZT to a human being with AIDS, nor did it perform the first clinical pharmacology studies in patients. It also did not perform the immunological and virological studies necessary to infer that the drug might work, and was therefore worth pursuing in further studies."

http://lists.essential.org/pharm-policy/msg00106.html

I hope the changes are made accordingly to provide insight into the actual work some of these scientists did.

Bassixx (talk) 07:41, 21 May 2008 (UTC)Bassixx