TESTING
In order to monitor the condition and progress of your cat there is a need to have diagnostic exams and laboratory work.
SCREENING TESTS
Viral load and CD4 counts are the present statistics that are used to measure the progress of the virus.
RT-PCR is used for viral load. Branch chain DNA assay for quantitative HIV plasma RNA levels. These test are also used to detect other organisms such as cytomegalovirus (CMV) and mycobacterium avium complex.
FIV-1 Quantitative RNA testing is useful in determining "viral load"-sensitive to 50 RNA copies/ml. After the first test the second viral load test should be done about four weeks later. If there is not a drop in viral load in using the formula, increase the amount or number on times formula is given. Test for maintenance of viral load should be given every four months.
CBC with Differential test is used for CD4 count and percent. Test for CD4:CD8 lymphocyte ratios, white and red blood counts.
This type of testing is expensive and should only be given when the cat is in an advanced state of AIDS. The DNA test cost presently about $110. A asymptomatic cat should be tested once a year for both viral load and CD4 counts.
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The following tests are also recommended:
Chemistry (Chem) Screen
Typically, 24 of these values are included in a Chem 24 Report also known as a SMAC or a SMA20. Chemistry Panel(SMA12, SMA14 or SMA20) test will reveal inflammation of the liver.
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Toxoplasma serolgy (IgG antibody)
Measure levels of vitamin B12, folate, magnesium and testosterone. Use supplements if deficiencies are found.
KITTENS
Some problems occur when testing. A negative test result indicates that the cat is not infected. However, it takes 8 to 12 weeks after infection (and sometimes even longer) before detectable levels of antibody appear. If the test is performed during this interval, inaccurate results might be obtained.
Another problem; Kittens with positive antibody tests must be retested when they are 6 to 8 months of age to determine their true infection status; as young kittens may have positive test results for 12 to 16 weeks after birth, without actually being infected with FIV, because of passive transfer of FIV antibodies from the mother. Only a small percentage of these kittens actually are or will become infected.
In a cat the antibodies gotten from mother disappear between 4-6 months, It is recommended retesting in three months both for positive and negative results for kittens.
The normal testing for FIV is to use ELISA followed by Western Blot test. The estern blot will confirm that the circulating antibodies are specific to FIV structural proteins. VITA-TECH Canada Inc announced that after several test trials they can confidently replace western blot confirmatory test for FIV ELISA positives with the more sensitive and highly specific FIV DNA test. DNA from feline blood cells can be extracted and tested to determine if any of these cells have been successful infected with FIV.
The information VITA-TECH puts out on ELISA follows:
First, Antibody levels must be above a certain threshold to generate a positive result. Second, antibody specificity may vary, and non-specific binding to non-FIV antigens may occur, producing a false positive. It is not known if cats can clear FIV once exposed. Therefore, a positive antibody test is not necessarily diagnostic of FIV infection. It is only diagnostic of exposure. Finally, passive transfer of maternal antibodies may result in a positive test in a kitten which is not infected.
In my medical immunology book is listed under testing children the following: Neonatal Diagnosis: Neonates with HIV infection pose a difficult serodiagnostic problem because maternal IgG antibody crosses the placenta. Thus, the infant passively acquires anti-HIV antibody, which may persist for up to 15 months. The predictive value of specific IgM antibodies in the diagnosis of neonatal and perinatal infection awaits clarification. Culture of the virus from peripheral blood or tissue or demonstration of HIV antigen is therefore necessary to be confident of the diagnosis of HIV infection in asymptomatic infants born to HIV-infected mothers, The PCR, which amplifies HIV genome present in cells or serum, provides a useful adjunct to diagnosis.
In general PCR must be performed at well-equipped laboratories by well-trained technicians. Poor sample handling can give mis-leading results. It is also important to remember that no test is 100% perfect all the time.
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COMPLETE BLOOD COUNTS (CBC)...normal range
Hematocrit (PCV) .............%................. 29-50
Hemoglobin .........,,,,.,,.g/dl.................... 9-15.6
Red Blood cell count x10(6)/u 1.............. 6.1-11.9
White Blood cell count..... /u 1................ 4,900-20,000
Neutrophils................./u 1.......................2,500-12,000
Lymphocytes................./u 1................... 1,500-7,000
Monocytes....................../u 1................... 0-850
Eosinophils..................../u 1..................... 0-1,500
Basophils....................../u 1..................... less than 100
Platelets....................../u 1....................... 190-800
Lymphocyte numbers, anemia, and emaciation are significant prognostic factors in analysis of FIV.
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T-4/T-8 (CD4/CD8) RATIO TEST
In HIV and FIV AIDS measurements of T-4/T-8 ratio are commonly used to monitor the progress of the disease. T-4 helper cels experience a decline , while T-8 suppressor cells generally increase early in the disease and decrease to normal levels later. As the disease progresses, the T-4/T-8 ratio declines. The ratio in normal persons is 1.8 to 2.3. For a moderately ill AIDS patient, the ratio ranges from 0.2 to 0.7, a level at which the patient can begin therapies with some expectation of improving the ratio. The closer the ratio approaches 0.01, the more difficult it becomes for the reserve capacity of the immune system to rebound.
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TESTING COMPLICATION
I had the experience recently where my cat Midnight that does not have FIV or Felv had a 105 temperature and could not identify what the virus was. Since there maybe 100 or more different viruses, some without names, I had to guess what treatment was best. The problem was it could have been bacteria since the blood counts were only a little below normal. When a blood count is less than normal it is a virus, above normal a bacteria infection.
The veterinarian give Baytril antibiotic that is used against bacteria to use for 10 days and I added Alpha Lipoic acid to treat the virus. The antibiotic also kills the flora which causes an imbalance in the stomach. I got nervous and went out and purchased a large bottle of Colostrum from the neighborhood GNC store. I couldn't wait for the order I placed on the internet to arrive through the mail.
I put a teaspoon full of Colostrum in a glass and added some water. I then used a syringe to put the mixed liquid into his mouth. To my surprise he liked the Colostrum. But it is something you have to force, as he is not going to voluntary drink it. I tried tasting it and didn't like it.
Midnights temperature went down after four days. I will never know where he got the infection from or what it was. Fortunately when a cat has a good immune system, the system deals with the infection. The problem with AIDS is there is a weak immune system to fight off infection and the more information you know, the better chance of fighting the infection. The problem with FIV is the blood count will be below normal because of the virus but will not indicate what the opportunistic infection is which complicates diagnosis and more special tests are needed. In the case of weight loss a gastroenterological specialist may be needed. In the case of Midnight I chose to treat the cat in a non-specific fashion. The veterinarian generally does not treat a virus which is why I had to add to the treatment given.
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In an e-mail I received on a four year old cat, the vet performed an in-office FIV/leukemia test and it had shown a very slight possibility of being afflicted with FIV. Then vet did a full blood screening and it showed that the cat red blood cell count was 8,(30 is normal) and his white blood cell count was 1.4 (10 is normal). This resulted in a blood transfusion and antibiotics treatment.
I had questioned whether the cat could be tested at a medical college but the owner lived in a small town, so retesting never took place and it was assumed the cat had FIV. I don't have much faith in the in-office test kit. I thought ELISA test should be confirmed.
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MEASUREMENT OF ANTIBODY LEVELS
... 2-6 yr senior 10-14 ranges(Plechner)
IgG 1600 1900 1000-2000MG
IgM 180 225 100-200MG
IgA 75 205 70-170MG
IMMUNE BASED DIAGNOSTIC TESTS
Cats respond poorly and unreliably to skin tests
Three most important immune based diagnostic tests that will indicate natural immunity against opportunistic infactions are the following:
1. Natural Killer Cell Function
2. Multitest CMI
3. B and T cell Function
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Multitest CMI
Connaught Labs in Swiftwater, PA
800-822-2463 or 717-839-7187
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Natural Killer Cell Function
Specialty Labs
Santa Monica, CA
800-421-7110....also does B cell Function test
or
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Immunosciences Labs in Beverly Hills, CA
800-950-4686 or 310-657-1077
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Multitest is a skin patch with several antigens like tetanus, candidine, diphtheria and others that prick the surface of the skin and insert a small amount of inactivated antigens. The skin patch test is read 48 to 72 hours later. This is used on HIV patients, whether a patch test for a cat is a good idea I don't know, but its available. Multitest is used to determine how a patients immune system is functioning. CD4 counts or PCR viral load are meaningless unless they correlate to improved immune function. As a surrogate marker, Multitest and other immune function tests are unsurpassed as a marker to determine the efficacy of any AIDS treatment protocol. A protocol that reduces FIV viral load but does not improve immune function treats FIV infection, butndoes not treat AIDS. An improvement in immune function is an indication that the protocol is working. Nice looking numbers, without function, will not protect patient from PCP, CMV, MAC. Improvements in immune function, even without nice looking numbers, will protect patient from opportunistic infections.
Anergy is an immunologically unresponsive state in which lymphocytes are presented but not functionally active. This is usually due to incomplete activation signals and may be an important regulatory mechanism in the immune system. e.g. tolerance of 'self' antigens. In AIDS, anergy could be induced due to HIV infection, e.g. interference with cytokine expression. There is experimental in vitro evidence that gp120-CD4 interactions result in anergy due to interference with signal transduction. Many AIDS patients are anergic, i.e. fail to mount a delayed-type hypsensitivity (DTH) response to skin-test antigens. Impaired DTH responses are directly related to decreasing CD4+ T-lymphocyte counts. However, there is no strong evidence that this phenomenon is directly related to any aspect of HIV infection in vivo rather than to general depletion of immune functions.
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HLA-DR+ is another "serum activation marker" for CD8 and CD4 cells (and other immune cells) which indicates their ability to respond to infections and to stimulate an immune response.
A protocol that reduces FIV viral load but does not improve immune function treats FIV infection, but does not treat AIDS. Nice looking numbers, without function, will not protect patient from PCP, CMV, MAC. Improvements in immune function, even without nice looking numbers, will protect patient from opportunistic infections.
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DNCB (dinitrochlorobenzene) is a chemical used to develop colour film. It has also been used in air conditiioning and refrigeration equipment. Medically, DNCB has been used as a crude test of CMI (cell-mediated immunity). For this purpose DNCB is usually dissolved in acetone and then put onto the skin. There the compound causes a minor allergic reaction, restricted to the small area where DNCB was applied. DNCB rapidly penetrates the skin and comes into contact with the cells of the immune system which carry the compound to the lymph nodes. Four hours after applying DNCB to the skin, the body has processed it and 53% of the chemical has been released into urine. About 48 hours after applying the chemical, CD4+ cells are thought to leave the lymph nodes producing chemical messengers such as IL-2, 12 and interferon-gamma that boost CMI. It is also thought that these CD4+ cells set off a similar reaction amongst some of the cells they encounter.
NOTE: Nguyen NL. Predicting the CD4 count from the result of dinitrochlorobenzen skin test using linear regression analysis. Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. B10437
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Tuberculin test will work for CMI response test
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WASTING
HIV related weight loss, often referred to as HIV wasting syndrome, is a common manifastation of advanced HIV infection. Wasting in HIV involves the preferential loss of lean body mass with a paradoxical preservation of body fat. The etiology of wasting appears to be the result of many factors, which may include decreased caloric intake, malabsorption, alterations in energy expenditure and metabolism, cytokine effects, and endocrine dysfunction. Pharmacologic treatment options include appetite stimulants (e.g., dronabinol, megestrol acetate), cytokine inhibitors (e.g., thalidomide, cyproheptadine, ketotifen, pentoxifylline, fish oil, N-acetylcysteine), and anabolic agents (e.g., testosterone, nandrolone, oxandrolone, recombinant human growth hormone)....Wasting associated with HIV was a high morbidity and mortality rate if not adequately managed. Therapeutic strategies include appetite stimulants, cytokine inhibitors, and growth-promoting agents. Selection of the appropriate agent(s) depends on the underlying cause for weight loss, adverse effects, and cost of therapy,
Weight loss is often a harbinger of secondary infection. In one study, rapid weight loss was accompanied by secondary infection 82% of the time. Slower weight loss was more associated with gastrointestinal disease (62% of cases). Therefore, careful workup for treatable OIs and GI disease is a priority when patients present with weight loss. Weight loss in AIDS patients may also directly correlated with decreased food intake, which must be addressed early and often in the course of treatment. Malabsorption may also play a role in weight loss.
Another cause of weight loss may be altered lipid metabolism. Free fatty acids released from the periphery are not oxidized and used for energy, but instead are resynthesized into triglycerides and stored again as fat. Energy is wasted each time fatty acids are re-synthesized, and skeletal muscle protein becomes the primary source of calories. Use L-carnitine to help with this problem. Carnitine acts as a shuttle, transporting fatty acids into mitochondria, the furnace of the cell, ultimately producing energy and clearing toxic wastes out of the cell.
A specific nutrient supplement, glutamine, was shown to improve body weight and restore body cell mass in pateints with AIDS wasting in a randomized, double-blind, placebo-controlled trial.
Some veterinarians are using "Winstrol" an anabolic steriod in dealing with wasting. They are also using "Immunoregulin" to strengthen immune system, but I don't recommand it. Don't use Winstrol which is immunosuppressive and long-term has bad side effects on cat. Try AndroGel
AndroGel developed by Unimed Pharmaceuticals
Blood serum (without cells) should be sampled for testosterone levels approximately 14 days after starting AndroGel.
AndroGel avoids potential liver toxicity
Testosterone patches are available as Testoderm and Androderm.
Deca Durabolin (Nandrolone Decanoate) for treatment of anorexia and anemia secondary to renal failure. 0.45 mg/ lb q 7 days IM.
Durabolin (Nandrolone phenpropionate) 10-20 mg/2 wk IM or subcut ..very expensive. Little less toxic than Deca Durabolin.
More toxic steroid is Oxymethalone (Androl 50) for anemia 0.05 -0.5 mg/lb sid PO.
All anabolic steroids have some potential for liver toxicity, especially with higher doses (except AndroGel), so your doctor should monitor liver function tests.
Supplements can help to protect the liver when taking oral anabolic steroids such as silymarin, Evening primrose oil, Omega 3 fatty acids NAC 600 mg Glycyrrhizinate Forte (Jarrow) 1/5 capsule, Alpha lipoic acid 50mg, glutamine powder, Denosyl, Lecithin, Liverite, Lung Tan Xie Gan Chinese herb formula - as directed.
Deer Antler is used for wasting and contains IGF-1
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I noted from one vet..Anabolic steroids
Laurabolin injection 2-5mg/kg every 21 days
Nandrolin injection 2-5mg/kg as a weekly injection
Nandoral tablets - one a day either whole or crushed into food
Retarbolin injection 1mg/kg every 21 days
Orandrone tablets 0.5mg/kg daily (the tablets are 5mg)
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Medline
"Effects of tapering doses of oral prednisone on viral load among HIV-infected patients with unexplained weight loss."
Given tapering does of prednisone over a 2-month period showed mean weight gain of 3.4 kg
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I have noticed that once veterinarians have tested for FIV and found the cat positive they don't test for opportunistic infections when the cat shows symptoms. You should get the veterinarian to test further to find what is getting the cat sick. FIV may destroy the immune system but it is another infection that is making the cat sick.
Tests for wasting are complete blood count (CBC) and a blood chemistry. You may want to do these tests quarterly so have a baseline for comparison. Test for AFB and fungal blood cultures and serum testosterone level.
Endocrine dysfunction - Disturbances in a variety of endocrine systems have been documented in patients with AIDS. A reduction in serum testosterone hormone concentration, adrenal dysfunction, and an alteration in thyroid hormone levels have been documented, especially in patients with severe wasting, although not consistently. Thyroid function may be "overstimulated" for the degree of wasting, thus potentially contributing to weight loss.
Chronic Diarrhea - A noninvasive evalution, including stool test results (bacterial culture, parasite examination), should be initially performed. Specific stool tests for cryptosporidia and microsporidia should be performed In patients with advanced AIDS. Testing for Clostridium difficile stool toxin should be performed in the appropriate setting. Blood cultures should be obtained in feverish patients and this should include mycobacterial culture. In patients with nonbloody diarrhea and negative stool test result, flexible sigmoidoscopy is a reseasonable next step. This is a direct examination of the interior of the sigmoid collon. Patients are at risk for cytomegalovirus colitis. Patients are also at risk for small bowel Mycobacterium avium complex infection. Chronic diarrhea is frequently accompanied by weight loss and fat malabsorption producing vitamin B12 deficiency.
Colostrum has been used to treat Cryptosporidia.
Hepatobiliary Disease - The liver is generally involved as part of a systemic opportunistic infection due to M. avium complex, fungi, or cytomegalovirus. Initial evaluation of blood or bone marrow specimens may provide an inferential diagnosis of liver disease.
MALNUTRITION
In a study with anorexia nervosa patients without HIV infection showed immunodeficiency. There was spontaneous high levels of circulating interleukin-1B (IL-1B) and tumor necrosis factor (TNF-a). It showed CD4+ reduction and cytotoxic CD8 increase and T-cell activation status (mainly the down-regulation of the CD2 and CD69 activation pathways). This finally leads to an impairment, not only in T-cell function but also in T-cell to B-cell co-operation. These immune alterations improve after refeeding and when nutritional status becomes less critical.
Malnutrition - Metabolic rate is typically measured by indirect calorimetry.
Cytokines - Tumor necrosis factor (TNF) has been suggested as a potential etiologic factor in FIV wasting syndrome. Studies using improved bioassays show elevated tumor necrosis factor levels in FIV-infected patients, which progressively increase with increasing immunodeficiency regardless of concurrent illness.
Amino acids are available in liquid form designed for IV/SQ use as total parental nutrition. CoQ10 will help in energy expenditure.
DE NOVO LIPOGENESIS (DNL) MEASUREMENTS
Using DNL to distinguish between starvation and metabolic dysregulation may be important. It has been demonstrated that body cell mass replenishment is possible in patients whose weight loss was due to malabsorption (starvation); in contrast, body cell mass replenishment is not possible in patients with systemic illness, Systemic illnesses, especially those due to an opportunistic infection or malignancy, cause metabolic dysregulation.
Unfortunately, DNL meassurement is not widely available and certainly not for a cat.
You are going to have to consider whether the wasting problem is from opportunistic infection and treat that infection in order to control wasting that is not simply a matter of starvation.
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Monitor for Malabsortion
The most commonly recognized micronutrient deficiency in HIV infection is Vitamin B12. This appears to be caused by defective intestinal absorption in many cases. Thus, replacement therapy often is ineffective. Productive HIV infection has nutritional consequences.
The use of L-glutamine may help to maintain absorptive capacity.
D-Xylose test measures ability to absorb sugars. Sudan Bluse Stein tests for statorrhea, or excess fat in bowel movements due to fat malabsorption.
As diagnostic techniques improved, sources of wasting were pinpointed in a number of clinical settings. Included were malabsorption caused by cytomegalovirus, cryptosporidium, and microsporidium as well as profound catabolic states caused by systemic illnesses, such as disseminated Mycobacterium avium complex infection and FIV-associated malignancies. With a loss of 34 percent of weight the feline is close to death. Treatments for opportunistic infections are clearly associated with improved survival and have also been linked to weight gain. Weight loss is a strong predictor of mortality.
Intestinal Permeability test.. Measures "Malabsorption" and "Leaky Gut syndrome".
Great Smokey Diagnostics 63 Aillicoa St. Asheville, NC 28801 800-522-4762
LEAKY GUT SYNDROME
Leaky gut syndrome is the name given to a very common health disorder in which the intestinal lining is more permeable than normal. The abnormally large spaces present between the cells of the gut wall allow the entry of viruses, bacteria, fungi and other toxic material into the bloodstream. In healthy circumstances the toxic material would be repelled and eliminated. In addition, undigested protein and fat also pass through the "leaky" intestinal wall where, instead of being used to aid the body, they now present a health risk.
Leaky gut syndrome is at least as common as all the immune system diseases put together. Basically, it is caused by inflammation of the gut lining.
Leaky gut syndrome creates a long list of mineral deficiencies.
Colostrum is effective in combating leaky gut syndrome. Its anti-inflammatory action plays a huge role in treating a leaky gut and it also repairs damaged cells, keeps the mucous layer of the intestines sealed and impermeable to toxin's
Acidophilus with Bifidum may help leaky gut syndrome.
I find that alternative medicine calls problem leaky gut syndrome, but looking at conventional medicine I am finding the term Crohn's disease used. This maybe a different disease with some similar problems. One treatment shown to improve Crohn's disease was intravenious immunoglobulin injection.
Crohn's disease is an inflammatory bowel disease (IBD), the general name for disease that cause inflammation in the intestines. Those herbs and drugs that are anti-TNF will be helpful in treating the disease.
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APPETITE STIMULANT
Cyproheptadine...Antihistamine, piperidine-type
Use: appetite stimulant in underweight clients and those with anorexia nervosa.
Inhibits excess cortisol created by FIV.
My veterinarian used Oxazepam when my cat Max stopped eating.
Herbs: Cayenne, Ginger, Black pepper, Gentian, Ginseng
Cayenne blocks substance P binding to macrophages inhibiting IL-6 and TNF
Up to 86% of all FIV virus in the body is in the intestines. Forty to sixty percent of all immune cells are in the gut. The first place CD4 cells are depleted is in the mucosal membranes of the intestines within the first few weeks after infection.
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FATTY ACIDS
Evening Primrose oil reduces symctium formation of FIV because of reduced cell adhesion. It also is said to inactivate the virus. The oil of this herb (EPO) is rich in gamma-linolenic acid (GLA). In studies done by researchers in Tanznia, the life expectancies of people who were HIV-positive were more than doubled by adding GLA and beneficial oils know as omega-3 fatty acids to their diets. On GLA most people take two to four capsules of EPO a day.
Omega-3 Fatty Acids (Fish Oils).....Is considered a weak cytokine blocker. Many of the cytokines and other factors that promote wasting are produced from a specific fatty acid present in the membrane which surrounds the cell. This fatty acid, arachidonic acid, can be partially replaced in the membrane by other fatty acids we ingest. Thus the factors that promote wasting are made in lesser quantities, or they are less effective. When we eat certain fish oils containing omega-3 fatty acids, we can facilitate this substitution.
Fish oil is a good source of omega-3 essential fatty acids. Salmon, mackerel, menhaden, herring and sardines are good sources of fish oil because they have a higher fat content and provide more omega-3 factors than other fishes. For instance, 4 ounces of salmon contains up to 3,600 milligrams of omega-3 fatty acids, while 4 ounces of cod (a low fat fish) contains only 300 milligrams.
Essential fatty acids in combination with sulphurated proteins may help restore health. Sulphurated proteins are present in cottage cheese. Without the vital combination of the essential fatty acids and sulphurated proteins, the production of hemoglobin (oxygen-carrying red blood cells), is impaired.
Looking at patent EP 0 524 796 A1.....which was the trial done on 12 patients in Tanz...Africa 1994.
Results CD4 baseline 59 +/- 12.5 week 8 261 +/- 63.7
That is a large increase in only 8 weeks. This done with combinatnion of (Primrose oil) omega-6 and omega-3. No test was given on viral load.
This I find surprising!!!! It is not something I find even mentioned in the literature except as example for alittle minor weight gain. Of cause in 1994 and somewhat after reconsitution was not the problem since everyone was dying and no protease drugs then.
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BONE PROBLEMS
Recent studies have documented a high prevalence of osteopenia in HIV infection.
Calcium supplement should be used to deal with bone mineral density problems.
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TABLE Decimal, Exponent, Logarithims(Log10)
100,000 105 5...10,000 104 4...1,000 103 3...100 102 2
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Viral Load reduction Conversions Table
The table below provides an illustration of how viral load reductions can be expressed in different terms
If an HIV-RNA value of 100,000(5.0log) copies/ml is reduced by:.
Log..........!Percent reduction......!Fold reduction...!Remaining viral load
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0.3 log.........50.0% reduction.......2-fold reduction.....50,000 copies/ml
0.5 log.........75.0% reduction.......3-fold reduction.....25,000 copies/ml
0.7 log.........80.0% reduction.......5-fold reduction.....20,000 copies/ml
1.0 log.........90.0% reduction.......10-fold reduction....10,000 copies/ml
1.5 log.........96.8% reduction.......32-fold reduction....3,200 copies/ml
2.0 log.........99.0% reduction.......100-fold reduction...1,000 copies/ml
2.5 log.........99.7% reduction.......316-fold reduction...300 copies/ml
3.0 log.........99.9% reduction.......1,000-fold reduction.100 copies/ml
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Use caution in interpreting plasma RNA copy numbers; the intraassay standard deviation is between 0.15 and 0.3 log.
For an individual child, less than a 0.5 log (3-fold) change may represent assay variability, and not true biologic difference.
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Standard measures are IC50 and IC90, referring to the concentration of drug that is required to inhibit viral growth by 50% and 90%, respectively.
