Author Topic: medications with unexpected antiretroviral properties  (Read 8977 times)

anciendaze

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medications with unexpected antiretroviral properties
« on: May 04, 2012, 06:07:50 PM »
This topic was sparked by a topic on PR claiming that "CFS is a bacterial disease" because some people treated long-term with doxycycline got better.  I posted the following there, and would like to extend my invitation to others to collect this information on a thread here: 
Quote
I've explored properties of a number of drugs people with ME are given in the hope of gaining insight into causes and treatments, without necessarily accepting the opinions which drive specific treatments. From painful experience over many years I have learned that few drugs are highly specific in their actions. (Psychoactive drugs are notorious for having multiple effects, so that the indications and side effects may swap places on pharmaceutical literature without changing the chemical at all.)

This has made me alert for evidence of effectiveness in cases which make no sense if you only consider the primary action of a drug. One of these showed up years ago in Japan when a patient was treated with minocycline for a urinary infection shortly after onset of acute schizophrenia, complete with hallucinations and delusions. The antibiotic appeared to not simply relieve the symptoms, but to cure the patient. This work was followed by trials in other countries which confirmed that sometime this antibiotic can head off the development of schizophrenia, if started early in the course of the disease. Note that some other patients treated in these studies had no apparent bacterial disease.

Further digging showed that Minocycline has some antiretroviral action. The chemical similarity between Minocycline and Doxycycline caused me to check the research on that. Doxycycline also has some antiretroviral action. Since many known retroviruses impair immune response, even specific activity of phagocytes dealing with bacteria, the correlation with bacterial infection could be a consequence of an undetected viral infection, not the primary cause of disease. This could have relevance to the use of long-term IV Doxycycline or Minocycline treatment for Lyme disease. The borelia spirochete could be part of a superinfection on top of an undetected slow viral infection. Parasites found in people with similar symptoms (babesia, giardia) could even be hyperinfections.

I'm still trying to track down evidence that other drugs given to patients with similar problems have weak antiretroviral properties. Acyclovir is sometimes used to treat patients with high titers of EBV, CMV or HHV-6. It has enough antiretroviral activity so that it has been proposed as a cheap generic which might be of use against HIV where more sophisticated and expensive drugs are unavailable. The interesting thing about this is that it only inhibits reverse transcription in cells dually-infected with HIV and EBV or another herpes virus. The conditions which produce antiretroviral activity are precisely the indications doctors using it to treat ME/CFS are looking for.

If anyone reading this has other reports of drugs given for any indication which surprisingly turn out to have antiretroviral properties I would like to hear about them. One example turned up in antiseizure medications, though the mechanism is more complicated. I recall hearing reports about antidepressant medications, but can't separate reports about improvements in the condition of AIDS patients taking them from the assumption that these improvements in proviral load are entirely the result of better patient compliance with other treatments. If you don't want to post here, send me a PM.

cath

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Wally

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Re: medications with unexpected antiretroviral properties
« Reply #2 on: May 04, 2012, 07:15:58 PM »
Just quickly scanning the latest posts on the Forum and saw this one.  I believe Ampligen is one of the drugs that some researchers/physicians believe may have anti-viral properties.  I have seen the hypothesis/research on several other drugs where it is believed they may also work as an antiviral even if not generally used for this reason.  Not feeling so great, so I will try to come back later and post any links I can find (unless this information is posted before I return from a reclining position).

:(  :-\   ???  :)

Wally
« Last Edit: May 05, 2012, 05:45:14 AM by Wally »

awol

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Re: medications with unexpected antiretroviral properties
« Reply #3 on: May 04, 2012, 07:39:22 PM »
there is already an outstanding thread on doxycycline's various advantages, including its anti-retroviral properties:

http://www.mecfsforums.com/index.php/topic,171.0.html
« Last Edit: May 04, 2012, 07:41:28 PM by awol »

anciendaze

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Re: medications with unexpected antiretroviral properties
« Reply #4 on: May 04, 2012, 09:28:04 PM »
Thank you, Cath!  Levamisol is one example of another kind of drug action I'm looking for. 
Quote
The key side toxic effect of the drug is agranulocytosis, a severe depletion of white blood cells that leaves patients vulnerable to infection.
One problem with reading medical literature is the variety of names you find describing essentially the same effect.  Depleting white blood cells is the mechanism of action of Rituximab, though it concentrates on CD20+ B cells. 

I've turned up another example, Clozapine (Clozaril), an atypical antipsychotic used to treat schizophrenia.  I had asked a doctor about drugs causing leukopenia or neutropenia, and discovered there was yet another term to search for.  He was not encouraging "agranulocytosis is a serious medical problem you are hardly interested in inducing for therapeutic effect."   He seemed to be missing the point that this some patients did experience marked improvement.  Like Rituximab it may be eliminating infected white blood cells.  The danger is obvious, you are dancing on a knife edge between eliminating infected immune cells and severely damaging the entire immune system, (if the hypothesis of infection is true.)  The problem is made worse because doctors don't know what is causing the patient's symptoms.  (This is one reason I have not rushed out to demand Rituximab treatment.) 

What this does give us is another way to look for reports of unexpected results.  Since schizophrenia, like ME/CFS, is of unknown etiology all existing drugs for it are very much the result of trial and error, even if some theory guided discovery.  It is possible the side effects were responsible for success in treatment.  If drugs which cause depletion of white blood cells can move the disease, and drugs which affect retroviruses can move the disease, the hypothesis of a retrovirus infecting white blood cells isn't completely nuts. 

Added:  I note yet again the curious relationship between drugs which affect viruses or cancer and drugs having an effect on "purely psychiatric" illnesses. 
« Last Edit: May 04, 2012, 09:36:59 PM by anciendaze »

cassea

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Re: medications with unexpected antiretroviral properties
« Reply #5 on: May 04, 2012, 09:30:06 PM »
Thanks Anciendaze, this is a good thread

since

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Re: medications with unexpected antiretroviral properties
« Reply #6 on: May 04, 2012, 09:50:02 PM »
I've turned up another example, Clozapine (Clozaril), an atypical antipsychotic used to treat schizophrenia.  I had asked a doctor about drugs causing leukopenia or neutropenia, and discovered there was yet another term to search for.  He was not encouraging "agranulocytosis is a serious medical problem you are hardly interested in inducing for therapeutic effect."   He seemed to be missing the point that this some patients did experience marked improvement.  Like Rituximab it may be eliminating infected white blood cells.  The danger is obvious, you are dancing on a knife edge between eliminating infected immune cells and severely damaging the entire immune system, (if the hypothesis of infection is true.)  The problem is made worse because doctors don't know what is causing the patient's symptoms.  (This is one reason I have not rushed out to demand Rituximab treatment.) 

I have read more than once that the ME/CFS patients that have had the most success with Valcyte also had the largest WBC drop.
Quality over quantity.

anciendaze

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Re: medications with unexpected antiretroviral properties
« Reply #7 on: May 04, 2012, 10:08:27 PM »
I have read more than once that the ME/CFS patients that have had the most success with Valcyte also had the largest WBC drop.
Another clue that the primary effect is tied to the side effect. 

I'm still hoping people will come up with examples of antidepressants with antiretroviral properties.  These are regularly prescribed for ME/CFS patients, and partial success is taken as proof the primary illness was depression.  I believe I've seen reports of antiretroviral activity, but I know better than to trust my memory. 

Several people have reported improvement on MAO inhibitors.  The problem here, besides the implication that the problem is depression, is that MAOIs have an incredible range of effects.  Isolating a particular biochemical pathway is difficult. 

Karin

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Re: medications with unexpected antiretroviral properties
« Reply #8 on: May 04, 2012, 10:16:37 PM »
Another clue that the primary effect is tied to the side effect. 

I'm still hoping people will come up with examples of antidepressants with antiretroviral properties.  These are regularly prescribed for ME/CFS patients, and partial success is taken as proof the primary illness was depression.  I believe I've seen reports of antiretroviral activity, but I know better than to trust my memory. 

Several people have reported improvement on MAO inhibitors.  The problem here, besides the implication that the problem is depression, is that MAOIs have an incredible range of effects.  Isolating a particular biochemical pathway is difficult.

Well ask and you shall receive!

J Neuroimmune Pharmacol. 2007 Mar;2(1):120-7. Epub 2007 Jan 3.
The role of cohort studies in drug development: clinical evidence of antiviral activity of serotonin reuptake inhibitors and HMG-CoA reductase inhibitors in the central nervous system.
http://www.ncbi.nlm.nih.gov/pubmed/18040835

"...
SRI users were less likely to have HIV RNA levels in CSF above 50 copies (c)/mL ... This association was most evident for three of the seven SRIs (citalopram, sertraline, and trazodone, or "antiviral" SRIs, ...) and was strongest in those not taking concomitant ART...
...
SRIs may reduce HIV replication in CSF and improve NP performance."

cath

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Re: medications with unexpected antiretroviral properties
« Reply #9 on: May 04, 2012, 10:19:44 PM »
Thank you, Cath!  Levamisol is one example of another kind of drug action I'm looking for.  One problem with reading medical literature is the variety of names you find describing essentially the same effect.  Depleting white blood cells is the mechanism of action of Rituximab, though it concentrates on CD20+ B cells.


I do not use levamisole because it can cause agranulocytosis.  I do it because it can restore T cell function and shift the Th2 to Th1.

Dosis is crucial. I can not bare high dosis but low dosis is very beneficial for me.

I am very much improved but I stilll need it every day. I think that is because it is an acetylcholine agonist and my acetylcholine system was significantly disturbed.



 

Karin

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Re: medications with unexpected antiretroviral properties
« Reply #10 on: May 04, 2012, 11:08:01 PM »
Chelating agents have anti-retroviral properties. This web site lists a bunch of references: http://autismcalciumchannelopathy.com/HIV_and_Autism.html

Disintegration of retroviruses by chelating agents - V. Wunderlich1 and G. Sydow1(1) April 1982. Central Institute for Cancer Research, Robert-Rössle-Institute, Academy of Sciences of the German Democratic Republic, Berlin, German Democratic Republic

Metal chelators as potential antiviral agents. Hutchinson DW. Antiviral Res. 1985 Aug;5(4):193-205 Klin Wochenschr. 1991 Oct 2;69(15):722-4.

Alpha-lipoic acid inhibits HIV replication - Grieb G. Med Monatsschr Pharm. 1992 Aug;15(8):243-4.

Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Baur A et al Klin Wochenschr. 1991 Oct 2;69(15):722-4.

Inhibition of Tat-mediated HIV-1-LTR transactivation and virus replication by sulfhydryl compounds with chelating properties - DEMIRHAN Ilhan et al. Anticancer Res. 2000 Jul-Aug;20(4):2513-7

Advances in two-metal chelation inhibitors of HIV integrase Authors: Johns, Brian A; Svolto, Angilique C Source: Expert Opinion on Therapeutic Patents, Volume 18, Number 11, November 2008 , pp. 1225-1237(13)

Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin. Georgiou NA et al J Infect Dis. 2000 Feb;181(2):484-90.

Thiamine disulfide as a potent inhibitor of human immunodeficiency virus (type-1) production - Shoji S et al, Biochem Biophys Res Commun. 1994 Nov 30;205(1):967-75.

For many years, chelation therapy ranked #1 in parent-rated effectiveness of biomedical intervention in autism (as evaluated by the Autism Research Institute based on parents' feedback), even though many in the mainstream world are strongly criticizing these methods.


anciendaze

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Re: medications with unexpected antiretroviral properties
« Reply #11 on: May 05, 2012, 02:35:03 AM »
Reports are coming in faster than I can follow up.  Don't feel neglected if I don't mention your contribution when you think I should.  I'm trying to give a variety of unexpected results a fair evaluation. 

Does anyone dare to claim they expected the one below? 
Quote
Life Sci. 1996;59(23):PL 365-70.

The effect of histamine type 2 receptor antagonists on human immunodeficiency virus (HIV) replication: identification of a new class of antiviral agents.

Bourinbaiar AS, Fruhstorfer EC. Metatron, Inc., New York, NY 10003, USA. emballon@usa.pipeline.com

The suppression of human immunodeficiency virus (HIV) replication by histamine type 2 (H2) receptor antagonists, cimetidine, ranitidine, and famotidine was examined in vitro. The 50% reduction (IC50) in p24 antigen expression caused by the anti-ulcer agent, cimetidine, was observed at 26.8 nM with IC100 at 10 microM. Unlike azidothymidine-a reverse transcriptase inhibitor-cimetidine blocked HIV infection without affecting cell growth, as no cytotoxicity was observed even at the highest 1 mM dose. Ranitidine and famotidine were less potent than cimetidine. H1 antagonists, cyproheptadine and diphenhydramine, had no effect on HIV replication. Although the activity of cimetidine was observed at concentrations attainable by oral administration, the mechanism of anti-HIV action is unknown. This is the first report on antiretroviral action of H2 blockers. Further studies are warranted to establish the potential of a new class of anti-HIV agents with immunomodulating properties.

BTW:  I'm old enough to remember the time when peptic ulcers were blamed on psychological problems. 

Levi

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Re: medications with unexpected antiretroviral properties
« Reply #12 on: May 05, 2012, 02:52:19 AM »
Quote
A Phase II study is currently underway comparing 48 weeks of Plaquenil against a placebo in HIV-positive people who have not yet started ARV therapy. The key research questions are whether Plaquenil is safe to use in these individuals and whether and to what degree it is able to suppress activation of CD8 cells.
http://www.aidsmeds.com/archive/Plaquenil_2578.shtml

Wally

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Re: medications with unexpected antiretroviral properties
« Reply #13 on: May 05, 2012, 06:45:44 AM »
Just quickly scanning the latest posts on the Forum and saw this one.  I believe Ampligen is one of the drugs that some researchers/physicians believe may have anti-viral properties.  I have seen the hypothesis/research on several other drugs where it is believed they may also work as an antiviral even if not generally used for this reason.  Not feeling so great, so I will try to come back later and post any links I can find (unless this information is posted before I return from a reclining position).

:(  :-\   ???  :)

Wally

Stopping by for a moment before I go back to hibernation mode under the covers.  I just did a quick goggle search on "Ampligen" and "Antiviral" and these are the links that popped up.

http://www.google.com/#hl=en&sclient=psy-ab&q=ampligen+antiviral&oq=Ampligen+Antivir&aq=0v&aqi=g-v1&aql=&gs_l=hp.1.0.0i15.541.16925.1.18974.36.18.15.3.3.1.631.3163.6j8j2j1j0j1.18.0...0.0.V0wxj4keRUc&pbx=1&bav=on.2,or.r_gc.r_pw.r_qf.,cf.osb&fp=b001bd3a40637c26&biw=1024&bih=599

Here is one of the links to an interview with Dr. Lapp. http://phoenixrising.me/cfs-chronic-fatigue-syndrome-me/immune/antivirals-and-immunemodulators/ampligen-rintatolimod/interview-with-dr-lapp-a-pioneer-and-patriarch-by-kelvin-lord

Wally

Karin

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Re: medications with unexpected antiretroviral properties
« Reply #14 on: May 05, 2012, 02:25:01 PM »
Thiamine disulfide is one of the chelating agents I listed above that also has an anti-HIV action. I had a closer look at this and found some interesting stuff:

1. A form of thiamine disulfide, Sulbutiamine, was found effective to treat 'astenia', which is a condition of chronic fatigue that is cerebral rather than neuromuscular in origin. It was found to cross the BBB and act on regions of the brain known to be involved in astenia. Sulbutiamine is available OTC.

http://en.wikipedia.org/wiki/Sulbutiamine
"In a study of 1772 patients with an infectious disease and asthenic symptoms, sulbutiamine was administered in addition to specific anti-infective treatment for 15 days.[12] The number of patients with complete resolution of all asthenic symptoms was 916..."

J Assoc Physicians India. 2003 Sep;51:891-5.
Adjuvant role of vitamin B analogue (sulbutiamine) with anti-infective treatment in infection associated asthenia.
https://www.ncbi.nlm.nih.gov/pubmed/14710977

Drugs Today (Barc). 1999 Mar;35(3):187-92.
Pharmacologic and therapeutic features of sulbutiamine.
https://www.ncbi.nlm.nih.gov/pubmed/12973384
"Sulbutiamine, a highly lipophilic thiamine derivative, is the only antiasthenic compound known to cross the blood-brain barrier and to be selectively active on specific brain structures directly involved in asthenia."


2. Some forms of thiamine disulfide have an anti-HIV action:

Biochem Biophys Res Commun. 1998 Aug 28;249(3):745-53.
An allosteric drug, o,o'-bismyristoyl thiamine disulfide, suppresses HIV-1 replication through prevention of nuclear translocation of both HIV-1 Tat and NF-kappa B.
http://www.ncbi.nlm.nih.gov/pubmed/9731208
"BMT inhibits nuclear translocation of both HIV-1 transactivator (TAT) and the cellular transcriptional nuclear factor-KB (NF-kappa B), resulting in the suppression of HIV-1 replication."

Biochem Biophys Res Commun. 1994 Nov 30;205(1):967-75.
Thiamine disulfide as a potent inhibitor of human immunodeficiency virus (type-1) production.
http://www.ncbi.nlm.nih.gov/pubmed/7999140
"The results suggest that thiamine disulfide may be important for AIDS chemotherapy."

I am not sure what exact form of tiamine disulfide is used in the above article...


3. Several forms of thiamine disulfide are available OTC:

- Sulbutiamine = O-isobutyrylthiamine disulfide: http://www.amazon.com/Grams-1-06-Sulbutiamine-Powder-Arcalion/dp/B005XOPLUW

- Fursultiamine = thiamine tetrahydrofurfuryl disulfide = TTFD: http://www.iherb.com/Cardiovascular-Research-Ltd-Lipothiamine-60-Enteric-Coated-Tablets/37107

- Allitiamine = thiamine allyl disulfide: found in garlic : http://www.iherb.com/Cardiovascular-Research-Ltd-Ecological-Formulas-Allithiamine-Vitamin-B1-50-mg-250-Capsules/25831
(Not sure here why TTFD is listed as ingredient in this allithiamine supplement, since those are supposed to be different forms)

Benfothiamine is not a disulfide form and it does not cross the BBB.

BMC Pharmacol. 2008; 8: 10
Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435522/?tool=pubmed

I have been taking benfothiamine for a few years, but I am thinking I might try to switch to a disulfide form of thiamine, might try all three of the above, especially since raw garlic has always been miraculous for me, but I rarely use it since it is so strong and corrosive for the upper GI.. One problem is I heard oral availability is very poor for TTFD...