VIREAD..TENOFOVIR
Efficacy of 9-(2-Phosphonylmethoxypropyl) Adenine for Therapy of Acute Feline Immunodeficiency Virus Infection
E.A. Hooverl, M.H. Mylesl, J.P. Ebnerl, R.J. Black2, and N. Bischofberger3
1 Colorado Sate University, Fort Collins, CO, U.S.A.; 2 Division of AIDS, NIAID, Rockville, MD, U.S.A., 3 Gilead SWciences Inc., Foster City, CA U.S.A.
To determine the efficacy of 9-(2-phosphonomethoxypropyl)adenine (PMPA) against acute and established chronic feline immunodeficiency virus (FIV) infection, cats were treated with PMPA (30mg/kg/day subcutaneously or 60 mg/kg/day orally) vs placebo either; (1) beginning at the time of challenge with either 1 or 10 cat infectious doses (CID) of FIV isolate FIV-B-2542; or (2) beginning 8 weeks after infection with FIV-B-2542 when infection was well established. All cats that received parenteral PMPA at the time of infection remained free of evidence of FIV infection (as determined by dilutional blood mononuclear cell coculture, polymerase chain reaction, and antibody assays) in the absence of mhematologic or other toxicity. By contrast, 100% of placebo-treated cats challenged with 10 CID of FIV became persistently infected and developed CD4 T cell depletion and symptoms of immunodeficiency. Oral PMPA therapy, although less effective than subcutaneous administration, still produced a 40% level of protection. PMPA therapy in cats with established infection reduced circulating viral burden. In summary, prophylactic PMPA treatment blocked FIV infection and prevented FIV-related disease and short term PMPA therapy prevented FIV-related disease in animals with established FIV infection. PMPA provided superior antiretrovral with substantially less toxicity than either AZT or 9-(2-phosphonomethoxyethyl)adenine (PMEA) in the FIV model.
Presented at the International Conference for Antival Research San Diego, California, April 5-10, 1998
Note: In studies of acute and chronic FIV infection in cats, tenofovir (30mg/kg/day) reduced ciculating viral FIV RNA but not PBMC-associated, co-culture-detected virus burden
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NucleomaxX
Study done in Dublin
METHODS
20 patients with HAL under stavudine or zidovudine containing HAART were randomized to receive either NucleomaxX, a dietary supplement which increases uridine serum levels (36 grams NucleomaxX TID for 10 days/month or placebo for 3 months. Body composition was measured using DEXA and MRI; liver fat by proton spectroscopy.
RESULTS
18 patients completed the study. No virological failure was observed. 1 patient discontinued NucleomaxX due to taste and one patient died of myocardial infarction in the placebo group. There were no statistically significant differences between the groups at baseline.
CONCLUSIONS
Uridine increased the amount of subcutaneous and visceral fat, and also increased blood pH and base excess in lipodysatrophic patients with unchanged antiretroviral therapy HAART, but did not change liver fat content or markers of insulin resistance.
Can be pruchased at www.e-nutrient.com
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HIV drug failure may turn out to be a good thing as it creates a weakened virus. Should read:
"Novel Viral Markers Predict HIV Disease Progression" by Eric S. Daar
It seems that Replication Capacity is changed when using HIV drugs that create mutations. Mutation K65r + M184v created by Tenofovir and 3TC have a 29% replication capacity versus the normal wild HIV virus. This may explain what happened when a FIV cat was on 3TC/ABC/Vread failed and switched to supplements and had a drop of viral load from 54,000 to undetectable. Normally when failing and stopping treatment the mutated virus returns to wild type and there is a decrease in CD4 along with increase in viral load. In this case it seems that with supplements and a weakened virus there was no return to wild type and viral rebound.
I have the feeling that this method would work for human that wanted to get off using HIV drugs and use supplements to suppress HIV virus. This based on weakening virus.
See www.geocities.com/joelkehler for supplements.
HIV PROTEASE INHIBITORS
TL-3 rights assigned to Optimer Pharmaceuticals.. BioMed Central shows the following study http://www.retrovirology.com/content/1/1/38 19 November 2004
Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3...John H Elder Sohela de Rozieres, Christina H Swan, Dennis A Sheeter, etc
Conclusions: The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at weeks post infection is indicative of a therapeutic effect of the compound on virus infection.
All TL-3 treated animals received 20 mg TL-3 by capsules at eight hour intervals, for approx. the first 7.5 weeks of the experiment. Dosage was then doubled to 40 mg TL-3 per dose at eight hour intervals for an additional week for the two control animals and the eight surviving animals in the TL-3 treated, infected cohort. No adverse effects were noted in the uninfected, TL-3 treated controls.
Experimental testing of new protease inhibitors in cats has been of limited success due to the ineffectiveness of HIV-1 specific protease inhibitors against FIV. The promising development of the protease inhibitor TL-3, which inhibits FIV, HIV-1 and SIV infections in vitro with similar effectiveness led us to analyze its efficacy in the cat model.
Resolution and Prevention of Feline Immunodeficiency Virus-Induced Neurological Deficits by Treatment with the Protease Inhibitor TL-3
John H. Elder, Salvador Huitron-Resendiz etc Journal of Virology, May 2004, p. 4535-4532
In vivo tests were performed to assess the influence of the protease inhibitor TL-3 on feline immunodeficiency virus (FIV)-induced central nervous system (CNS) deficits. etc....The findings show that early TL-3 treatment can effectively eliminate FIV-induced changes in the CNS. Furthermore, TL-3 can counteract FIV effects on the CNS of infected cats, although continued treatment is required to maintain unimpaired CNS function.
Dose 2 X 20 mg of TL-3 orally at 8 a.m. and again at 4.30 p.m.
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HIV protease inhibitors inhibit proteasome.
Inhibited proteasome will not degrade IkB of NF-kB which activates replication of FIV virus. And because of inhibition of proteasome the FIV virus will not mature when it assembles and exists from cell. It has created faulty particles which will not work.
The HIV protease inhibitor will not show a decrease in viral load short term but you will see an increase in T-cells.
Proteasome inhibition strength follows: sequinavir>lopinavir>ritonavir>atazanavir>indinavir
A new cancer Velcade (bartezomib) has been designed to inhibit proteasome
None of the above drugs has been tested against a FIV cat. It should be noted that Green Tea inhibits proteasome.
NRTI INHIBITORS
AZT creates anemia so use Mitocnol (NucleomaxX) which contains Uridine. AZT/NucleomaxX not yet tried for FIV
Abacavir
Viread
You can use Agaricus, Glycyrrhizinate Forte, Green Tea Phytosome to give better inhibition to single NRTI
DDI/Hydrea..... Hydrea toxic to bone marrow
Abacavir/Hydrea
Better is dual
3TC/abacavir
3TC/Viread
add Green Tea Phytosome and Glycyrrhizinate Forte. Herbs entry inhibitors
3TC/Abacavir/Viread
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Omega Interferon-manufacturer Virbac
Make in Europe
Site: www.dierenziekenhuis.nl (in Dutch)..E-mail infor@dierenziekenhuis.nl
vet name Dr. Emil Visnjaric-oral version
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J Acquir Immune Defic Syndr 1993 Feb;6(2):127-34
Prophylactic ZDV therapy prevents early viremia and lymphocyte decline but not primary infection in feline immunodeficiency virus-inoculated cats.
Hayes KA, Lafrado LJ, Erickson JG, Marr JM, Mathes LE
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.
Prophylactic zidovudine (ZDV) therapy was evaluated in the feline immunodeficiency virus (FIV)-inoculated cat model for HIV-1 infection in humans. ZDV treatment (30mg/kg/day via contiinusous subcutaneous infusion) was initiated 48 h prior to virus inoculation and continued for 28 days. Transient plasma antigenemia evident in six of six untreated cats at week 2 post-inoculation (pi) was absent in the ZDV-treated cats although at 10 and 14 weeks pi (6 and 10 weeks after drug treatment), one of the ZDV-treated cats had low-level antigenemia. Both CD4 and CD8 lymphocyte numbers were consistently higher in the ZDV-treated cats when compared to both the FIV-inoculated untreated cats and the virus-naive, age-matched controls. CD4:CD8 ratios were lower for the ZDV treated cats than either the FIV-inoculated untreated or virus-naive, control cats. The decreased CD4:CD8 ratios were the result of an increase in CD8 lymphocytes in the ZDV-treated cats while decreased ratios in the FIV-inoculated untreated cats were due to cell loss. Both ZDV-treated and untreated cats showed nearly identical FIV-specific antibody responses beginning 2 weeks pi. Polymerase chain reaction (PCR) results from blood lymphocytes showed that six of six ZDV-treated and six of six untreated cats were positive for FIV-specific gag sequences. Although primary infection was not prevented, these results suggest that prophylactic ZDV therapy deterred early systemic spread of infection mediated by viremia and delayed absolute CD4 and CD8 lymphocyte decline.
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In study of early suppression of viremia by ZDV by Hayes that lasted 12 months it showed: While prophylatic ZDV treatment prevented detectable plasma antigenemia and FIV-induced CD8 lymphocyte decline, it did not slow infection of tissues and blood cells of FIV-inoculated cats. They did not have viral load tests at this time. But PCR was showing FIV DNA in blood, lymph node, bone marrow, spleen, thymus and brain from FIV-inoculated cats irrespective of ZDV treatment.
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Therapeutic Effects of Zidovudine on Cats Infected with Retrovirus
Gomez Nelida Virginia, etc
The main objective of this project was to assess the therapeutic effect of Zidovudine (AZT) on cats infected with either FIV or Felv at late but not terminal stages of the respective diseases.
10 FIV, 3 FeLV and 15 healthy. Treatment with AZT was attempted at an oral dose of 5 mg/Kg, TID during 5 weeks with resting intervals of 4 weeks.
RESULTS: Most of the patients (80%) underwent 2 years of treatment.
CONCLUSION: Controlling FIV or FeLV infections could be achieve by means of anti-retroviral therapies. The use of AZT at 5 mg/Kg TID proved to be effective and safe. However, a tight follow up on patient's conditions should be done including hemograms and determination of CD4/CD8 rates.
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Medline Abstract
Long-term treatment of diseased, FIV-seropositive field cats with azidothymidine (AZT).
Zentralbl Veterinarmed A 1995 Aug;42(6):397-409 (ISSN: 0514-7158)
Hart S; Nolte I
Clinic of Small Animals, Hanover School of Veterinary Medicine, Germany.
The long-term effectiveness of Azidothymidine (AZT, Zidovudine) was evaluated in FIV-seropositive cats with clinical symptoms (n=9; Group 1) compared with conventional symptomatical therapy (n=5; Group 2). The oral administration of Azidothymidine at a dosage of 5 mg/kg BW yielded a mean peak plasma concentration of 4.59 microM one hour after application (median: 3.74 microM). Elimination half time was 1.5 h. The permanent oral application of Azidothymidine at a dosage of 5 mg/kg BW TID led to a total recovery from clinical symptoms in six of nine FIV-serpositive cats (Group 1) 4-6 weeks after the onset of therapy. One cat clinically improved with only sporadical recurrence of disease; therapy with Azidothymidine was not effective in two cats. All the FIV-seropositive cats treated symptomatically responded well to antibiotics and immunomodulators within 10-14 days (n=5; Group 2). Recurrence of clinical symptoms was noticed in three of five patients within 2 years after therapy and one cat died. During the treatment with Azidothymidine hyperproteinemia and abnormal albumin-to-globulin ratio became normal within 6 months in four FIV positive cats (Group 1) whereas hyperproteinemia did not change in Group 2. The following adverse effects were noticed in Group 1: a transient decrease of red blood cell count (RBC), packed cell volume (PCV) and haemoglobin until the 4th week of application of Azidothymidine (5/8), but the haemogram was within the normal range after 3 months. In one cat with hyperglycemia the anaemia remained until the administration of Azidothymidine was terminated. Heinz (Schmauch) bodies in the erythrocytes appeared in two FIV-positive cats 2 weeks after the onset of the therapy.
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FROM ESSAY ON CAT PUSH THAT USED DDI PLUS HYDREA
Hydrea/ddI peaked at six months then returned to baseline on cat Push at 12 months.
Hydrea 1000 mg
20 =50mg ONCE daily per 3 kg cat.
Dosage (FOR HUMANS) on ddI.
The dosage of these drugs when used for treatment of humans is based on a 60 kg man as follows:
ddi. 200 mg twice daily (supplied as 100 tablets).
How to calculate dosage for your cat. Divide the weight of your cat into the weight of the 60 kg man to find out how many times smaller you need to make the cat's dosage. For example, if your cat weights 3 kilos, then the equation is...
60
3 - 20
Now divide the human dosage by twenty...
ddI 200mg
20 = 10 mg twice daily per 3 kg cat.
Doage - Important notes on the use of ddI.
DDI. Use only 100 mg tablets as the basis for treatment.!
DDI is available in a variety of sizes of dosage (25, 50, 100 & 150 mg). All are the same size tablet. All contain the same amount of magnesium/aluminium antacid. Only the amount of ddI varies and the number is clearly stamped on the tablet. The purpose of the magnesium/aluminum is to create an antacid condition in the stomach. The more antacid, the greater the absortion of ddI into the body. The higher the levels of ddI, the higher the toxicity. For example, a single 100 mg tablet is not the same as four 25 mg tablets, which would have four times the antacid.
After trial and error, it was discovered that the 100 mg tablets were effective with acceptable toxicity. It is easy to crush the tablet to a powder and divide it into the dosage required for your cat. Medication should be given on an empty stomach one hour before meals. (BMS now state that a minimum of 30 minutes before meals is sufficient). If the drug is given with food or on a full stomach, absorption will be reduced by 50%. DDI can be given at 12 hour intervals.
The easy way to get the drugs into your cat is to remove the plunger from a 10 ml syringe. Pour in the drug powder, replace the plunger and fill the syringe with about 1 ml of water. Shake it and then place the syringe (without needle!) into the side of the cat's mouth just behind the canine teeth and squrt it in, slowly, allowing the cat to swallow. Do not squirt it down its throat, or it will choke. This should be followed by perhaps another 10 ml of plain water.
Main side effects of DDI. (Always read the drug information leaflet supplied by the drug manufacturer).
The medications come with manufactuers' informtaion. However, it is necessary to discuss details of some of the main side effects and how to monitor these in your cat. DDI is manufactured by Bristol Myers Squibb. Amongst its side effects, you will need to be mostly concerned with:
1. Pancreatitis. This is a known complication which can be life threatening. Signs are pain in the upper abdomen, nausea and vomiting. Also, elevations in serum amylase levels, which can be measured in your vet's lab. Normal serum amylase levels for a cat are 0 to 2600 u/dl (u=milli-units). Push has been as high as 3600+ with no ill effects. Labs will vary and so will individual cats. (Lipase is another method used to assess this condition.) Once, Push recorded an amylase figure of 5800 when we originally used the 25mg size tablets of ddI! (Use ONLY the 100mg size). At this point, she experienced pain on palpitation of the abdomen and we ceased medication. Since we corrected the dose and type of tablet used, there has been no problem. The above dosages are from the benefit of experience, so you should be okay. But check regularly for any rise in amylase figures and check for side effects.
2. Peripheral neuropathy. Put simply, this is pain in the nerve ends and extremities such as the paws, for example. No problem here with Push.
3. Liver failure. Moderate elevations in ALT (SGPT) were noted in Push, though these were not thought to be significant. It is well to monitor them nevertheless.
4. Immune system suppression. Leucopenia and thromboctopenia.
A. Leucopenia. This is fewer than normal white blood cells, (leucocytes), usually due to bone marrow function being impaired by the drug. Note that this is also one of the major effects of FIV itself. White blood cells are responsible for fighting infections. Its important to commence treatment whilst this and other components of the immune system are still reasonably intact, as the antiviral drugs may suppress leucocyte numbers further. Though as already state, this effect was found to be transitory and temporary. Again, individual cats will vary.
B. Thrombocytopenia. The thrombocytes are basically platelets responsible for blood clotting. Insufficient numbers may result in hemorrhaging, (internal bleeding), obviously most serious. FIV suppresses thrombocyte numbers and the antiviral drugs is likely to make this worse. However, as you will see from Push's test results (look for complete essay on internet), she remains reasonably stable. You will need to assess the state of your cat's immune system prior to treatment and continue to monitor this until you are sure the blood picture is stable. Your vet can arrange the necessary blood tests. Clearly it is advantageous to commence treatment whilst the patient still has a resonably intact immune system.
C. Anemia. Fewer than normal numbers of red blood cells. The red blood cells are responsible for carrying oxygen around the body. Insufficient numbers result in weakness, shortness of breath and pale skin. (Check the skin colour inside the ears and also colour of the gums). In Push's case iron supplements were found to be effective, though this is only of help in certain types of anemia and will depend upon the root cause. Folinic acid supplements may also be of help. Erythropoeitin may help in cases where the anemia is caused by renal failure.
For full details of all side effects, read the drug information leaflet, supplied with the medications thoroughly and show it to your vet.
NOTES on Hydrea from Push article.
Hydrea 1000 mg
20 =50 mg ONCE daily per 3 kg cat.
Hydrea comes in 500 mg capsules, which you will need to open and then divide the contents to arrive at your required dosage. It is not so easy, since it is a slighly sticky crystalline substance and you will be dealing with tiny amounts.
Wear a mask! These drugs are toxic and carcinogenic, so you don't want to inhale the fine powder whilst you are working with it. Keep them safe and dry and away from heat. Always check the expiry dates before using. Overdose is dangerous!
Main side effects of Hydrea. (Always read the drug information leaflet supplied by th manufacturer)
Hydrea is also manufactured by Bristol Myers Squibb. Originally used in high doses to treat cancer, the significantly lower dose required to treat HIV or FIV is less toxic. The main side effect of Hydrea is that it is myelosuppressive. That is to say, it depresses the production of blood cells by the bond marrow. Notably this may cause leucopenia, thrombocytopenia or anemia. It is notable that FIV can also cause similar effects and you'll need to differentiate between immune suppression caused by the virus and immune suppression caused by the drugs! Your vet can help with this by doing blood tests to monitor the condition. Its most important to carry out a CBC (Complete Blood Count) prior to commencing treatment so you'll have baseline figures to refer to later. But apart from a transient effect during the first two weeks of therapy, we had no problems with Push. This is remarkable, considering that her immune system was already somewhat depressed due to the effects of FIV. There are those who suspect that Hyrea's suppession of the immune system may actually be of benefit as it leaves fewer target cells for the virus to attack. However, the other side of this is that fact that the immune system is less likely to rebuild whilst the patient is on Hyrea. Some other antivirals allow reconstruction of the immune system to take place to some extent, but they all appear to have unacceptable failings. Put simply, the less damage that has been done to the immune system and the sooner you commence treatment, then the better your chances of success.
If your cat's immune system is already very low and the patient is suffering from a variety of opportunistic infections which have already gone beyond the mild to the severe stage, it may be beneficial to commence treatment with antivirals like ddI, perhaps adding d4t too, possibly for the first month or so to allow the immune system a chance to recover prior to adding the immunosuppressive Hydrea. But remember, without Hydrea resistance to the antivirals will ocur. No one knows everything about this and my best suggestion to you is to discuss it with your vet and monitor the patient's blood test results as a guide. Remember that despite antiviral therapy you will continue to get opportunistic infections if the immune system is already damaged, and this situation is not likely to improve much whilst taking Hydrea. It should, however, improve whilst taking ddI and d4T.
Side effects: Lencopenia, Thombocytopenia, Anemia are shown above with DDI.
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COMMENT
Hydrea inhibits FIV dendritic but not activated lymphocytes cells.
Nevirapine does not work for cats.
HIV drugs after a year or two fail in 50% of the HIV cases because of mutations.
On the article on cat Push mention is made of D4T. I do not show any documentation on either D4T or 3TC for cat trials. Protease or NNRTI drugs developed so far do not work for a cat with FIV. Both AZT and Hydrea suppress bone marrow. AZT/3TC does not work for chronic FIV. Fatal hypersenitivity reactions are a described risk associate with use of abacavir (Ziagen). 3 to 5% hypersensitivity reactions. This is treated with glucocorticoids.
In one study for human HIV at 24 weeks DDI/Hydrea 500mg/Hydroxychloroquine 200mg N=23 undetectable n=6.
I don't know how safe or toxic D4T is for a cat.
NOTE: 3TC does not have the toxicity to mitochondrial that other NARTI have. It comes in 150 mg tablet. Have not found documentation on its use for cats, except vitro test. I did find dideoxycytidine 5'-triphosphate (DDC) documentation for cats but this was also vitro.
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Hydroxychloroquine...inhibiting posttranscriptional modification of HIV
Study on 2 patients with AIDS and inflammatory arthritis. dosage 600 mg a day. result at one year, there was a 1-log decrease in recoverable HIV-1 RNA, improved mitogen- and antigen-specific immune responses.
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PATENT WO9660988
COMBINATION THERAPY FOR TREATMENT OF FIV INFECTION
INVENTORS ARAI MAKI; DUNN BEN M; YAMAMOTO JANET K
EXAMPLE 2 PROPHYLACTIC EFFICACY OF AZT/3TC IN CATS
Four of the eight SPF cats (16-20 weeks of age) received oral administration of AZT and 3TC (75 mg/kg each) twice a day (BID), while remaining cats received placbo.....
At 4 weeks of treatment, severe anemia was observed in all challenged and unchallenged cats treated with AZT/3TC; therefore, the doses of each drug were lowered to 34 mg/kg each at 4 weeks of treatment and subsequently to 5-10 mg/kg each at 5 weeks of treatment. AZT/3TC treatment was terminated in one cat at 6 weeks of treatment, and the treatment was resumed 6 days later at 5 mg/kg each.... Both drug and placebo treatments were terminate at 11 weeks pi and all cats were monitored for additional 6-13 weeks....
All AZT/3TC treated cats remained negative for FIV in PBMC and anti-FIV antibodies throughout the 6-13 weeks after the withdrawal of the drug treatment. Virus isolation and PCR of bone marrow and lymph node cells performed at the termination of the study further confirmed the FIV-free status of these cats. Thus, complete protection of cats against experimental FIV infection was achieved with prophylactic AZT/3TC therapy.
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We have a year-old cat (found in a dumpster at months) that tested FIV+ after a series of high fevers every month for several months. After considerable research, our vet put her on 1.25 ml. of AZT for nine weeks during which she showed no clinical symptoms. Now, our vet has her on two weeks on/two weeks off 1.25 ml. of AZT with Vitamin B supplements. She has gained a pound, has a beautiful coat and is acting like a normal kitten after several months of being a very quiet kitten. Would it be helpful to add Vitamin E and C to her supplements? We will do ANYTHING for her-she is a wonderful little cat.
COMMENT
Cat getting 1.25 ml of retrovir syrup at 10Mg/ml = 12.5 ml of AZT twice per day
At first recommended Alpha Lipoic 50mg, Pet Tab, Laktoferrin with Colostrum. Then amino acid arginine and lysine which raises the level of thymulin and growth hormone to create more CD4 cells I also recommand the use of Glycyrrhizinate Forte (Jarrow) 1/5 capsule.
The problem with AZT alone is inflammation continues to destroy the thymus, so an anti-inflammatory drug is required which in this case is Glycyrrhizinate Forte
When a cat gets anemia using AZT and stops with a short break then starts again; many times the cat will adjust to the drug and can continue to use it
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Cat from Sri Lanka weight 3.2kg with diabetes and low lymph count
868 07/23/02,
1410 11/11/02,
4320 03/18/03 ..CD4 655 CD8 1078
HIV drugs used:
Tenofovir 30mg a day
3TC 6mg twice a day
Abacavir 24mg twice a day
omega interferon high dose
Herbs: Colostrum, L-Lysine, L-Carnitin, Gluthathion, Viola Clear Fire, Resveratrol synergy, Laktoferrin, Shitake, Alpha lipoic acid, Taurin, SAMe, Tym-Uvocal, Xobaline, Co-enzyme and ubichinon, bactisel, Ipakitine
Aspirin, insulin, antibiotics
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Abacavir Hypersensitivity
Symptoms reported in HIV in 20% of cases of this multiorgan reaction included fever, rash, malaise/fatigue, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea, among others. Respiratory symptoms occurred in 30% of cases and included dyspnea (12%), cough (10%), and pharyngitis (6%) In 90% of cases, hypersensitivity reaction occurred within the first 6 weeks after initiation of abacavir (median time, 11 days),after an initial reaction, rechalenge with abacavir resulted in the reappearance of symptoms within hours of reexposure....Hypersensitivity to abacavir is an absolute contraindication to subsequent treatment with any formulation that includes this agent.
Tenofovir may cause kidney damage
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RESTORATION OF IMPAIRED CELLULAR IMMUNE FUNCTION
John Fahey UCLA 1991
..The vast majority of lymphocytes demonstrate defective function. Drugs currently approved for treatment of HIV-infected subjects are all aimed at inhibiting viral replication and none are aimed at restoring the defective immune cell function.
The current invention discloses methods and compositions for the restoration of impaired immunity resulting from HIV infection. Significant increases in intracellular cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity have been quantified in T lymphocytes from HIV seropositive individuals. By lowering the intracellular levels of cAMP and, therefore, cAMP-dependent PKA, the specific immune function of T cells taken from HIV seropositive subjects can be restored in vitro assys. These data suggest that cAMP levels may be beneficial in the treatment of AIDS. Compounds that are effective in the assays of immune function are inhibitors of various steps of the cAMP/PKA pathway. Examples include 2,5-dideoxyadenosine and an extract from the Chinese herb dan-shen.
See Patent 6,429,208
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COX-2 creates Prostaglandin E2. There are two new drugs that inhibit COX-2. But better still Zyflamend that contain herbs does similar inhibition of COX-2.
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Neurotoxicity of B-Lactam ANTIBIOTIC
There is no research on toxicity of antibiotics for feline. Because of this many cats are killed without vets knowing why
IL-2
In order for drug IL-2 to replicate it must be cycled and not use all the time otherwise a switch is turned on which stops replication. This is not true with low dose IL-2.
