Bud’s “Second Chance”: Lifetime FIV Therapy
2. Asymptomatic Phase
3. Symptomatic Phase
4. AIDS Phase
5. Maternally Derived Infection
6. Checklist: Choosing among FIV Therapies
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What follows is a prescription for FIV therapy based on (1) lessons learned from the therapy I have actually done, (2) accounts I have read of therapeutic outcomes for other FIV+ cats, and (3) deductions from research that I have read. It assumes that the Guidelines and Medications and Supplements pages on this site have already been read. In his Autobiography, Benjamin Franklin, imagining a second chance at living his life, “only ask[ed] the advantage authors have in a second edition to correct some faults of the first.” This is, in a sense, my “second edition” and Bud’s imagined “second chance” to get a coherent FIV therapy, rather than one constantly concocted to stay ahead of the break of the wave. For the better part of Bud’s life, the idea that there was something I could do to affect its quality and quantity never occurred to me. When I finally did become proactive, I made “errata” aplenty. The program of therapy laid out here represents only what I would do if the clock could be turned back. No therapeutic approach is without some element of risk with uncertain rewards. The person who takes an aspirin a day for his heart’s sake runs a heightened risk of dying from internal bleeding or may have a heart attack anyway. If his response is therefore to do nothing, so be it. On the other hand, the familiar refrain “There’s really not much you can do about FIV” is 180 degrees from the truth. The real problem is that there are so many things of potential value, narrowing the field to a manageable “best” few is very difficult.
Part and parcel of turning back the clock is the possibility of a number of infection scenarios and disease progressions that might have been the case. Any “program” must recognize that no single course of therapy is appropriate to all situations. I have therefore outlined therapeutic
strategies for different situations and have laid out what seem to me acceptable options within those strategies. My belief, however, is that it makes more sense to seek to prevent problems than to try to remedy them once they have occurred.
Each part of the program described within is accompanied by a “discussion” of issues raised and the thinking that might go into addressing those issues. I have generally not taken a prescriptive stance, but if I have personal inclinations, I have indicated what they are and have labeled them
as such. Because “maternally-derived infection” (i.e., infection of a kitten before, during, or after birth as a result of lactation, often called “vertical” infection) is a special case, I have created a special category for it and dealt with it last, even though a cat thus infected will, at any given time, fall into one of the categories that precede. I have also offered “Optional Menus” describing possible add-ons or substitutes for agents listed on the Program menu. “Optional Menus,” may contain items that are mutually exclusive. The Section 6 Checklist attempts to provide a basis for making admittedly difficult choices. Each menu offers an “ideal” program that many would regard as beyond their capacity to implement. Since most people are receptive to one or two OTC supplements in addition to any prescription drugs, each menu has two supplements highlighted in blue that represent options I would most strongly consider using at that stage of infection
Dosages are not offered for any Programs. Dosages of agents I have used can be found on the
Medications and Supplements page of this site. But dosages in many cases are guesswork. For additional discussion and research references for some of the following agents, see the “read more” links on the Therapeutic Guidelines and Medications and Supplements pages.
2. Asymptomatic Phase
An “average” cat infected as an adult or near-adult by a bite wound usually has a number of years of uncompromised health to look forward to. Studies have shown, however, that subtle deficits exist in such cats from an early point of infection forward. Coordination, for instance, is
measurably impaired as a result of damage to the central nervous system. Damage to the thymus may leave behind permanent impairment of the lymphatic system. Both systems are known to be reservoirs of virus–and so, presumably, of viral activity–even when measurable virus in the peripheral blood is scant or altogether lacking. FIV-related cancer has often been reported clinically and experimentally in cats who have otherwise shown no other FIV-related problems; the same is the case with certain types of kidney disease.
For these reasons, addressing the disease status of outwardly “perfectly healthy” looking cats is not unreasonable. HIV studies have shown that people beginning therapy earliest stand the best chance of seeing their immune parameters return to those most like uninfected people’s. There are almost no “lifetime” studies of FIV+ cats, to the best of my knowledge, for purposes of determining whether any agents significantly delay disease advancement. Moducare is perhaps the most thoroughly tested product; researchers associated with the patent holder have followed the progress of infected cats for many years. No figures have been published, however, dealing with this particular point. It has been neither proven nor disproven that anything will delay onset of symptoms. However, a number of commonly available agents have been identified as having an impact on HIV infection, seeming either to delay onset of symptoms, favorably affect viral load, or initiate immune activity that might conceivably result in such delay. Since the asymptomatic phase of FIV infection may last for many years and since cats are notoriously unhappy and uncooperative about being medicated, care during this phase is best entrusted to agents that can have bearable taste and that can be given in food, syringed in a liquid or thinned food medium, or applied to the cat’s paws or mouth for “clean up” ingestion. Although I have come to believe that the greatest good the owner of an FIV+ cat can do for it is to get it used to taking pills, I realize that this is a difficult step for owners and a disturbing process of adjustment for a cat. Agents whose long term impact is an unknown, possibly worrisome matter are best avoided.. This program is built primarily around antioxidants, anti-inflammatories, and immune-modulators
Because FIV+ cats may not remain asymptomatic indefinitely, and because a cat, once symptomatic, does not usually return to unsupported asymptomatic status, a strategy at least available for consideration is to break with a preventative Program at some point and begin to incorporate at least some elements of a more aggressive care such as that delineated in the ARC-Phase Program–in spite of a cat’s current asymptomatic status. A cat who goes beyond eight years or so without showing symptoms of his infection should be considered fortunate–although this is certainly not unprecedented. A further complication, however, is that most FIV+ cats are former strays, and unless they were young when taken in, the owner often has little idea when they were infected.
Vitamin C---------------------------Odd-Numbered Months-------------------Twice daily
Melatonin---------------------------Odd-Numbered Months-------------------Once daily
Lactoferrin--------------------------Every Month----------------------------------1x or 2x daily
Vitamin E---------------------------Odd-Numbered Months--------------------Alt/days or 2x/wk
Vit B Complex----------------------Even-Numbered Months------------------Once daily
Methylated Vitamin B12----------Even-Numbered Months------------------Daily or alt/days
L-Carnitine/Acetyl-L-Carnitine--Even-Numbered or Every Month-------1x or 2x daily
Alpha Lipoic Acid------------------Every Second or Third Month------------Once daily
Probiotic-----------------------------Every Month----------------------------------Once daily or divided
CoQ10------------------------------When not using ALA or any time---------Once daily
Moducare---------------------------Every Month-----------------------------------1x or 2x daily
Niacinamide------------------------Even-Numbered Months w/B Comp----1x or 2x daily
Licorice/Glycyrrhizinate----------Even-Numbered Months------------------1x or 2x daily<
Selenium----------------------------Even-Numbered Months-------------------Once daily
Green Tea or Curcumin---------Odd-Numbered Months--------------------1x or 2x daily
Thymus Peptides-------------------Odd-Numbered Months------------------Once daily
Oral Human Alpha-Interferon----7 days on, 7 days off----------------------Once daily
(Recombinant or Natural)
Low-Dose Prednisolone----------Every Month---------------------------------Once daily
Olive Leaf---------------------------Every Month----------------------------------1x or 2x
1. Rotating and discontinuous use of supplements is a concept I have come to by degrees. Too much is not known about long-term effects of most supplements in people, much less in cats. One phenomenon whose scope is still being uncovered is the conversion of antioxidants to prooxidants with prolonged use at substantial dosages. Short term behavior of supplements does
not necessarily predict long term behavior. Likewise, demonstrable benefit against HIV or FIV is no guarantee that deficits are not created in other areas of health. Long term supplementation can also interfere with natural processes. Cats, for instance, manufacture their own Vitamin C and
Melatonin. It has, for instance, been proposed that prolonged high dose supplementation with the first can create dependency and cause “rebound scurvy” in people who stop suddenly, particularly to the fetuses of expectant mothers. So it is at least conceivable that native production of Vitamin C (and Melatonin) might be affected by prolonged administration to a cat. Expanding the menu of supplements allows coverage at any given time, while allowing significant amounts of down time for individual agents. (And obviously, a cat can only get so many supplements.) Up front costs may be larger, but eventually they are recovered.
2. FIV+ cats frequently develop inflammatory conditions as a result of skewed immune response. Proinflammatory cytokines and chemokine upregulation promote injury to local cell populations. Lactoferrin is a very useful supplement in this, as well as many other regards–It may be the single most indicated supplement for an FIV+ cat. If I were to give only one FIV-specific supplement, this would be it. It has been associated with increased risk of at least one type of human cancer (beneficial for other types), so, depending on one’s level of prudence, either continuous or discontinuous admin is defensible. Lactoferrin’s gut-associated immune activity argues for its use early on in FIV infection since the intestinal epithelium and lamina propria are early sites of infection and long-term reservoirs of virus.
Pathological changes in intestinal tissue are observable from an early point of infection.
3. Carnitine has a proven ability to prevent T cell “apoptosis” (induction of programmed cell-death). This may stem from its antioxidant/ TNF-α downregulating or mitochondria-support qualities, but one study also found a suppressive effect on secretion of IL-12, a co-stimulant for CD8+ T cell maturation by monocytes and macrophages. How this action should affect use of Carnitine is unclear, since it has been so widely endorsed as HIV and FIV therapy. In HIV studies, IL-2 alone has been found insufficient for maintaining T-cell responsiveness in symptomatic, but sufficient for asymptomatic, individuals; in the former instance, exogenous IL-12 was also required. However, another study found that Carnitine (in combination with NAC and ALA) fostered CD4+ gains and viral load declines in HIV+ individuals both on and off HAART with drug-related peripheral neuropathy. It is unclear how many (if any) of these patients had advanced HIV symptoms. It is therefore at least possible that Carnitine is more indicated for asymptomatic than symptomatic cats. L-Carnitine in red meat has recently been linked to atheroschlerosis (plaque-related heart disease) in humans and in laboratory mice. As obligate carnivores, cats ordinarily lack the human liability to plaque-related, cholesterol-related heart disease.
4. FIV+ cats can suffer neural damage over time. Melatonin and B12 may provide protection against neurological effects of FIV infection, and might provide continuous coverage if
alternated. B12, however, is better given in a sublingual formulation, dissolved in a bit of water and dropped under the tongue. Adding a Vitamin B Complex alternately with the B12 is an attractive option. Niacinamide (the amide form of Niacin), which raises levels of serum trypophan and which has shown antiviral and anti-apoptotic properties in HIV studies, could be given concurrently. Human research validates a dose about 3-4 times the RDA, which would be around 100-120mg daily for a cat.
5. At least one major antioxidant may be a good idea for any FIV+ cat. Alpha Lipoic Acid (sometimes called the Universal Antioxidant) probably has more potential as a useful antioxidant for HIV infection than CoQ10. However, the latter has a good track record of safety in cats. Continuous use of the first is terra incognita, and dosage is important since both neurotoxicity and hepatotoxicity have been shown in cats at certain dosage levels. Providing coverage with CoQ10 when ALA is not being used has some appeal. However, since
CoQ10 regenerates Vitamin E and Vitamin E concentrates CoQ10 in the liver, one may wish to give it concurrently with E and C.
6. Human HIV and animal FIV studies have found that Probiotics decrease production of the inflammatory cytokine TNF-α in the gut, help to quiet chronic immune activation caused by translocation of microbial products across the intestinal epithelium, and either preserve or improve CD4+ T cell populations and the retrovirally skewed CD4:CD8 ratio.
7. More recent analysis by researchers associated with the marketing of Moducare has emphasized the ability of the product’s phytosterols to hold to a lower but adequate level the T cells infected by the FIV, thereby allowing for less infection. Claims of the latter strategy were nowhere in evidence in early studies, which emphasized T cell preservation and population
growth. But the outcomes consistently claimed in studies of people and cats are worthy of note. Moducare seems to produce a better comparative clinical outcome when given to cats without poor CD4+ lymphocyte numbers. It should be remembered, however, that Moducare studies have been done giving that product alone; interaction of Moducare with other supplements could conceivably negate its value. Moducare also has anti-inflammatory and immune-balancing effects. Polyunsaturated fatty acids (PUFAs), such as fish oil or evening primrose oil, also have therapeutic value by exercizing anti-inflammatory, immunosuppressive effects on both nonspecific and specific immunity through modulation of cell membrane lipid-protein interactions, inhibiting downstream signaling responsible for T cell activation and proliferation. This strategy (perhaps like the use of Moducare) may become less desirable when viral loads are high and/or when CD4+ cell counts are low, but research shows that it makes sense for asymptomatic cats.
8. The taste of herbs needs to be taken into account if one plans to give them long term. Licorice, Green Tea, and Curcumin have valuable antioxidant and anti-inflammatory properties. Curcumin inhibits the primary viral co-receptor. Licorice and Green Tea may also inhibit the primary co-receptor. Therefore pairings may make sense. In moderate dosages, these are relatively benign herbs. Licorice and Green Tea are best not given at the same time for extended periods. Optimized forms of curcumin and green tea (for instance, Phytosomes in which the herb is bound to phosphatidyl choline) significantly increase bioavailability and should always be preferred. Recent revelations that Green Tea is potentially harmful to humans in large doses over periods of time may argue for once daily administration, moderate dosage, and irregular treatment intervals.
9. Broad Immune Stimulants should not be given to asymptomatic cats. They may inadvertently raise viral loads, increase T cell apoptosis and provoke inflammatory disease processes, while seeking to solve a problem that does not yet exist.
10. Varying degrees of damage to the thymus, home to T cells, characterizes all FIV infection.
Thymus Peptides have demonstrated some ability to assist in production of CD4+ and CD8+ lymphocytes and to potentiate the cell-mediated immune response generally. The extent to which relatively unrefined oral products affect T cell proliferation and cell activation is unclear. Whether a refined product such as Thymic Protein A, which has been shown to induce T cell proliferation via direct IL-2 stimulus, would be appropriate for an asymptomatic cat and if so by what treatment protocol, will have to await further study. Thymic “involution” (decline in normal functioning) occurs in FIV+ cats, so some type of thymic support makes sense. HIV research suggests that thymus peptides might be of particular usefulness early, when thymus function still exists to support, than late, when naive thymocytes are no longer being generated.
11. Human Interferon-Alpha (huIFN-α) given orally in a recent study showed clinical benefit in ARC- and AIDS-Stage cats. However, the interferon was of a mixed natural variety cultivated from human cell lines, not the recombinant variety currently commonly used. The likelihood is that asymptomatic cats would also experience benefit from this interferon, although recombinant interferon might have some prophylactic value for asymptomatic cats. Pet owners have reported long term supplementation (eight years, in one case) without evident harm.
12. Low-Dose Prednisolone has been validated in HIV medicine as an appropriate therapy for asymptomatic individuals with viral loads below 40,000 and CD4+ counts above 400. There are several possible modes of beneficial activity, but retarding apoptosis of lymphocytes due to activation is likely one. It is difficult to say what complements steroid therapy. Cats receiving low-dose prednisolone (.5 - 1 mg daily) should probably not receive supplements such as licorice, which acts in a steroidal manner. Supplements such as NAC, Carnitine, and Melatonin, which also inhibit apoptosis may or may not complement low-dose prednisolone.
13. Olive Leaf Extract (OLE) has so many potentially favorable activities in an FIV+ cat that there is a temptation to say that all FIV+ cats should get it their entire life. The nagging uncertainty is how much credit to give anecdotal accounts that its impact on FIV is term limited. Unless or until this issue is settled caregivers may wish to save it for a “rainy day”–or, at least, a later one. The person who does choose to give it should probably give it every day and twice a day for maximum benefit, though once may be a necessary compromise for a nonhuman.
3. Symptomatic Phase
One of the conundrums in dealing with FIV lies in recognizing when some pathological process is related to FIV infection and when it isn’t. An FIV+ cat who shows signs of stomatitis and excessive gingivitis or who develops recurrent upper respiratory or eye infections should be regarded as symptomatic. Chronic diarrhea is a somewhat more difficult call since an independent Irritable Bowel Disorder is always a possibility. Many disorders with an allergic or autoimmune component (because of the high level of immune activity provoked and sustained by the virus)–diabetes, some early-appearing kidney disease, lymphocytic-plasmocytic IBD, and some types of liver disease.–“probably” owe some of their impetus to FIV. Infections of major organs such as the kidney, the bladder, and the liver should be regarded with suspicion. So should bacterial or fungal skin infections and recurrent abscesses. Depending on a vet who knows that your cat is FIV+ to identify what is “symptomatic” is risky, since many vets blame everything that happens to an FIV+ cat on the FIV– it makes the job a lot easier! Still, one should err on the side prudence and assume that pathologies common where FIV infection exists “probably” derive–at least in part– from it. Such a cat should be considered “symptomatic”– even if it isn’t!
FIV progression to the ARC-Stage has two major components: (1) a loss of T-Helper lymphocyte numbers and efficiency (a general decline in white cell count may or may not be evident) that impairs immune function and (2) a skewed immune response, meaning a predominance of inflammatory cytokines (immunoregulatory proteins) such as as TNF-α and Ifn-γ and excessive B cell recruitment for antibody synthesis. Increasing viral load is partly, but not wholly, responsible for both developments. Derived from HIV medicine, the term ARC (AIDS-Related Complex) puts the emphasis on pathologies that develop as natural outgrowths of FIV or HIV infection. (Some analysts extend PGL–Persistent Generalized Lymphadenopathy–to cover a period of isolated and discontinuous symptoms.) Such pathologies almost invariably require medical measures aimed directly at them. But ignoring theroot from which they stem makes no sense to me. This is never done in human medicine; it is done, much more often than not, in veterinary medicine.
Effective address to this phase of FIV infection should take into account all three drivers: T4 loss and inefficiency, inflammatory immune processes, and viremia (virus increase). This is not always easy to do, however, because agents that offer improvement in one or two of these areas can create problems in the remaining area or areas. Careful choices need to be made with an eye to the particular pathologies originating (even if only in part) with FIV infection
The Program for asymptomatic cats never completely expires and, within the dictates of practicality, all elements of it remain desirable for ARC-Stage symptomatic cats. That would hold for a cat who had no therapy while asymptomatic or for one who already used some of the agents already cited. HIV research has shown, for instance, that the effect of antioxidants was most profound in highly immune suppressed individuals. If, say, I had been using NAC and ALA, I would increase dosing schedule to at least 50% of the time. Depending on the perceived level of disease progression, other agents from the Program for asymptomatic cats might be raised nearer to or to 100% of the time; some given once a day might be given twice. The following situations don’t comprise all possibilities and can overlap, as for instance when the first two are linked by
chronic viral infection causing oral problems and URTI.
For cats with diseases of the oral cavity or other inflammatory diseases
Feline Omega Interferon
Lactoferrin (Full time)
Group 1 Herbs: Most likely to be safe for long-term use (Twice Daily if feasible. Unfortunately, cats with oral pain are difficult to medicate, much less supplement. So this regime may not be possible until inflammation has been suppressed)
Ketotifen or Pentoxifylline
NAC (N-acetylcysteine) or SOD/Oxstrin
Group 2 Herbs: Less likely to be safe for long-term use (Equal or more time off as on)
SPV-30/Boxwood (Not more than 3 months)
Green Tea (Every other month. See note to Discussion Point #3)
Bitter Melon (Not more than 2 months)
Oral Natural Interferon-α
For Cats with Chronic Gastrointestinal (including Liver and Pancreatic) Inflammation
(See Chronic Diarrhea)
Same Program menu as above (especially Enhanced Curcumin and Licorice/ Glycyrrhizinate), no Bitter Melon or Green Tea
For Cats with Refractory Infections
Same Program menu as above (especially Olive Leaf and Lactoferrin), no Green Tea
Lymphocyte T-Cell Immunomodulator (Thymic Protein A) a possible substitute for Feline Omega Interferon, particularly when infection not viral
Same as above, no ketotifen or pentoxifylline
Staphylococcus Protein A (SPA)
*Do not use if giving acemannan
For Visibly Degenerating Cats with a History of FIV-Related Pathologies;
For Cats with Pathologies Unresponsive to the Above
Tenofovir (TDF) and
Lamivudine (3TC) or Emtricitabine (FTC)
Zidovudine (AZT) (Supplemented with NucleomaxX and Resveratrol)
Feline Omega Interferon
Lymphocyte T Cell Immunomodulator
For Cats with Neurological Symptoms
Abacavir (ABC) and Lamivudine (3TC)
One or more of Melatonin, Resveratrol, DHEA
Zidovudine (AZT) (Supplemented with NucleomaxX and Resveratrol)
1. Feline Omega Interferon is the heaviest weapon in the arsenal for combatting the combined problems of FIV and oral inflammatory disease. It is not a miracle drug, and published studies suggest a measurable but modest impact on long term survival. However, in cats suffering from secondary viral infections and/or inflammatory pathologies it is a major development in
improving the quality of life. Pentoxifylline and Ketotifen are weak anti-inflammatory immunomodulators that have shown usefulness when part of a larger program. None of these agents has significant impact on white cell deficits. Lactoferrin has proven value in this situation and should be given full time, at least until the inflammatory process is under good control.
2. NAC, especially when used in conjunction with Vitamin C, has demonstrated a number of actions antagonistic to FIV infection, mostly through the ability to normalize intracellular glutathione deficiencies stemming directly from FIV. These include preservation of CD4+ cells from apoptosis, increasing or maintaining CD4+ cell numbers, and increasing activity and reactivity of several arms of the nonspecific immune response (neutrophils and macrophages). It has also shown the ability to lower viral loads in HIV patients with low CD4+ cell counts. Various studies have raised questions about possible downsides to NAC, though none conclusively, and NAC does have low bioavailability, so significant amounts must be given for oral supplementation. It would seem, at the least, that it should probably not be given to asymptomatic cats. It is possible that NAC’s other benefits might outweigh possible detriments (if there are any) in cats with more advanced disease. Studies do suggest that NAC can also elevate glutathione levels in the brain, reducing inflammatory cytokines, so may be of possible benefit for neurological complications. SOD (superoxide dismutase) is a related antioxidant enzyme that (when given as the proprietary supplement Oxstrin) has also been shown to raise intracellular levels of glutathione in the T cells of FIV+ cats and raise CD4:CD8
ratios. SOD catalyzes the reaction that takes the superoxide free radical, the most damaging free radical, to hydrogen peroxide, which in turn is catalyzed to water by glutathione peroxidase. Oxstrin couples SOD molecules with a protective protein derived from wheat and other plants, so that they can be delivered intact to the intestines and absorbed into the bloodstream without degradation by stomach acid. Although it’s unclear whether NAC or SOD/Oxstrin is the superior supplement and whether SOD shares any of the potential downsides of NAC, Oxstrin does have the advantage of superior uptake.
3. Olive Leaf, Licorice, Green Tea, and Grape Seed all have TH1 (antiinflammatory) cytokine profiles and all are antioxidant. Bud’s experience has shown that collectively his herbal and nonherbal supplements are highly viricidal. However, there is no way of knowing which supplements or combination of supplements is most potent. Curcumin has shown useful anti-inflammatory activity in the mouth and bowel. Although its value as an FIV therapy is not entirely clear, one may wish to make some use of it when FIV-related inflammatory diseases are present. Prunella, now being available in a standardized powder extract, is a suitable add-on to any combination. SPV-30 and Bitter Melon, whatever their effect on viral load or immune response, have not been credited with TH1 cytokine profiles, although each has some antiinflammatory properties. Again, one could make a decision to avoid these herbs, but (1) Licorice and Green Tea are best not used concurrently all the time because of potassium depletion, and (2) Green Tea may cause iron deficiency if used constantly on a long-term basis and inhibits expansion of Helper T’s, so it may be more appropriate for asymptomatic cats with fewer immune deficits or for those in need of antiinflammatory activity. The principle of rotation implies something equally as effective as the thing it is replacing be available. So a hard choice is in order regarding herbs with suspect long-term effects. I would make limited use of Curcumin, at the least.
(*Note: Because they both have TH2 (antibody-inducing) action and because there is contradictory data on whether Green Tea and Curcumin are synergistic or antagonstic in various pertinent regards, it might be prudent not to use them at the same time.)
4. Piperine (pepper extract) is very useful in helping green tea, curcumin, and some other herbs become bioavailable. However, data is lacking on the long term effects of piperine in cats. My view now is that it should be used no more than 50% of the time. When available, phytosome products might be used, and mixing with lecithin, oil, and casein probably improves bioavailability for many such supplements.
5. Immunoregulin, Baypamun, and SPA are all unproven at this time as FIV therapies, though each has qualities of potential value in supporting a flagging immune system. It is unclear at this time what kind of effect Lymphocyte T Cell Immunomodulator (LTCI) has on inflammatory conditions such as stomatitis. None of the other agents should be a first choice when clearly inflammatory pathologies are occurring; they are unlikely to help and some may worsen the situation. Because its initial action is purely to activate and prime Helper T cells, Lymphocyte T Cell Immunomodulator’s narrowly targeted IL-2 stimulus may make it the most desirable of the stimulating agents. Studies have provided encouraging short-term data, but have not yet clarified long-term effects. Cimetidine (Tagamet) and Melatonin are complementary sources of IL-12. (IL-2 and IL-12 are both necessary for maturation of cytotoxic "killer" T cells.) Because (at least in one study) Acemannan worked as well given orally as when injected, it may deserve more consideration than it now gets, but a version for oral administration is not available. Ambrotose and Beta Mannan (sold as Man Aloe) are aloe preparations that may be taken orally, though they lack validation by studies in FIV+ cats. Because of the need for regular injections, which were given intravenously in the leg, Bud became increasingly unhappy about receiving Immunoregulin. The value of Immunoregulin to deal with short-term problems might outweigh its downside; for long-term maintenance the regimen is hard on a cat and of uncertain value at this time. SPA (at 10-50 mcg/2.75kg IP or IV) as been tested largely on cats with FeLV and has shown some impressive results . As an FIV therapy, SPA lacks objective data, and for whatever reason (possibly the advent of Immunoregulin), interest in it for that purpose seems to have flagged. Baypamun has no bona fides as a primary FIV therapy, but may be a short term option in periods of illness.
6. Beta Glucans, whether in bulk form or in various mushroom supplements, have some value in stimulating production of T cells and NK cells. Whether their broad action is desirable where inflammatory pathologies exist (since they upregulate the inflammatory cytokine TNF-α) is open to question; where they don’t, they are a possible tool in the arsenal. Beta Glucans are said to deplete Vitamin C in macrophages; hence, the two should be given together.
7. Abacavir, the HIV NRTI, crosses the blood-brain barrier and kills virus in the Central Nervous System. If my cat were showing neurological symptoms of FIV, I would use it. To what extent it would stall the process I cannot say, but a recent study has shown that a single NRTI (ddI, which also crosses the bbb) prevented microglial activation and depletion of synaptic proteins in the cortex of FIV-infected cats. An earlier study established Abacavir and Lamivudine as the most efficient NRTIs within the CNS, so there is a good chance that abacavir can do what ddI does. Used in concert with antioxidant supplements such as Melatonin and B12 that have shown some value with CNS HIV, it is a good gamble. The same is the case with DHEA and Resveratrol, the latter of which has shown a potent anti-inflammatory effect on CNS microglial cell-activation, is potentiated by Melatonin and shows synergy with it in anti-neurodegenerative effect. Curcumin has recently been shown to protect against HIV-associated cognitive impairment in a rat model, although penetration of blood-brain barrier varies with species. Antioxidants generally may be useful (including Vitamin E, NAC, and Alpha Lipoic Acid). Grape Seed Extract has antioxidant properties that function across the bbb. Luteolin prevents activator protein-1 (AP-1) from binding the promoter of inflammatory "cytokine" IL-6, thereby inhibiting inflammation in brain microglial cells. Prednisolone has proven of benefit with HIV-related neurological symptoms, but low-dose might not be adequate. Cost-benefit of immunosuppression vs neurological benefit would have to be weighed. Phenobarbital has been used with some success in FIV+ cats with neurological problems. The antibiotic Minocycline showed action against HIV-induced neurological problems in one study, and might have short-term utility in dealing with an FIV-induced situation.
8. For discussion of timing in the use of NRTIs (HIV antivirals), see the following program for the Symptomatic (AIDS) Phase. Although Zidovudine can be used alone or in combination with Lamivudine, an eight-week study of several years ago did not find significant potency in that combination alone. Although the study failed to measure free virus loads (RNA) and although its conclusions are seemingly at odds with those arrived at in other studies, this might be a prompt to add Abacavir to form the triple combination that performed well against FIV in vitro in another study. The cost of triple combinations is obviously a factor. Personally, I cannot see any reason, at this time, to prefer any two-drug combination containing Zidovudine to one containing
Tenofovir. Olive Leaf has been found to be compatible and synergistic with several NRTIs and should be included in any NRTI regimen, since it provides viral inhibition at a different point in the replication cycle than NRTIs. Several studies have suggested that strategically selected herbs (mulberry, astragalus, licorice, artemesia, and safflower in one HIV study) can boost both the virus-suppressing and CD4+ cell-enhancing capacity of a two-NRTI combination.
4. AIDS Phase
It is difficult to assess the distinction between Late-ARC and Early-AIDS Phase of FIV infection. For therapeutic purposes, the two might be treated the same. White cell and/or red cell counts that stay below normal upon repeated testing and cannot be accounted for by other pathologies suggest AIDS-stage infection. Viral load and CD4 counts, in any given instance, are helpful, but not definitive, indicators.
A cat that has entered the AIDS phase of infection requires the highest degree of intervention if its life is to be prolonged at a quality level. The earlier, the better. Once serious bone-marrow suppression by the virus sets in, progenitor cells are lost and bringing the cat back for more than a brief period is extremely difficult. Major organ failure may likewise be irreversible. Any supplements appropriate to an asymptomatic cat remain available for use at this stage, but will make little or no difference if used by themselves. The presence of compromised organs needs to be taken into account, as well, in ruling out use of some supplements. The Program for Asymptomatic Cats never completely expires.
Lamivudine (3TC) or emtricitabine (FTC)
Melatonin or Resveratrol
Zidovudine (AZT) (Supplemented with NucleomaxX and Resveratrol)
Feline Omega Interferon
Lymphocyte T Cell Immunomodulator
For cats suffering leukocyte (white cell) deficiency
Astralagus, Millettia/Marrow Plus, Lactoferrin
Immunoregulin–for mildly low white cell counts
Niacinamide, Neupogen (synthetic Granulocyte-Colony Stimulating Factor, or G-CSF)–for Neutropenia
Lymphocyte T Cell Immunomodulator–for red- and white-cell deficiencies
For cats suffering red-cell deficiency
Carao, Milletia/Marrow Plus
Epoetin Alfa, Darbepoetin Alfa
1. The HIV antivirals cited in combination cansuppress viral replication and contribute to improved health for only so long. For this reason use of NRTIs should not even be contemplated until there is significant evidence of markedly compromised health. Once they are begun, they should not be stopped unless there is an intention to use them no further. By the same token, waiting until it is too late for anything to help makes no sense to me either. Late ARC or early AIDS is the time to pull the trigger. If I were using the TDF/3TC or TDF/FTC combination, I would use higher mg/kg dosages than I did first time around. Bloodwork needs to be closely monitored for evidence of possible anemia, liver, or kidney compromise, but I do not
believe that these will be seen at a moderately increased dosage. Even after NRTIs no longer work, there is an argument to be made for continuing use of Lamivudine, perhaps at a lower dosage, since the mutated virus that overcomes it is less potent than the wildtype.
2. One study showed that a combination of three antioxidant micronutrients–N-Acetylcysteine,
Alpha Lipoic Acid, and L-Carnitine–raised CD4+ counts by an unexpected 26%. Gains were registered for those not receiving antiretroviral drugs, as well as for those receiving them. A cat
with AIDS must be presumed to be radically deficient in CD4+ lymphocytes, regardless of whether counts are available. Antiretroviral drugs stop CD4+ declines and may reverse them. But experience in HIV medicine is that CD4+ rises often do not proportionally match decline in viral burden.
3. Someone who, for whatever reason, inclines to use of Zidovudine/AZT, alone or in the combination cited, should consider supplementing with NucleomaxX in hope of raising uridine levels and avoiding AZT-associated anemia. It is an experimental supplement still in testing. I do not see how it can do harm; it might not work or it might even debase the effect of the AZT. It would be a gamble, but one I would take. Resveratrol is likewise a gamble. Several NRTIs have shown enhanced bioactivity when coadministered with the antioxidant resveratrol. Resveratrol has been demonstrated to activate resting CD4+ memory cells, allowing depletion of the pool of latent virus; however, for this same reason it has also been shown to increase viral burden in the absence of viricidal agents.
4. Cytokine dysregulation and proinflammatory immune response are large problems at all stages of FIV infection. There is no reason not to use (or continue using)
Interferons or other agents (such as
LTCI) aimed at this facet of the disease at the AIDS stage.
5. I have no wisdom to offer as regards choosing to try the multi-herbal therapy that was outlined in ARC Phase and that resulted in undetectable virus in my case. Perhaps it would work, but I would use no less than 5 herbs. It is possible that prior use of NRTIs creates a weaker strain of virus that enhances the action of the herbs
6. When white and red cell counts fall to low levels, several natural products can provide some
help. However, thinking only in terms of adding cells rather than addressing the entire disease is a mistake. Millettia and Astralagus have both been used to address leukopenia, principally involving neutropenia. Astralagus, however, has also been shown to lengthen the cell cycle of lymphocytes. Lactoferrin improves functionality of neutrophils. Its homeostatic role in the neutrophil cycle is complex and not completely understood. Since it suppresses both G-CSF (granulocyte-colony stimulating factor) and GM-CSF (granulocyte macrophage-colony stimulating factor), possibly it should not be given when neutropenia is being addressed with proliferative stimulants. Possibly by multiple mechanisms that include suppression of negative iron-blocking effects of the proinflammatory cytokine IL-6, Lactoferrin restores iron export to bone marrow, improving “anemia of inflammation” (also called “anemia of chronic disease”) secondary to chronic viral infections and cancer. Carao, a dried powder from the fruit cassia grandis, has, when coadministered with iron, improved production of hemoglobin. A milletia-containing proprietary herbal blend called Marrow Plus often improves anemia, possibly by stimulation of erythropoietin production. For severe deficiencies of red or white cells, synthetic versions of human hormones such as Epoetin (erythropoietin) and Neupogen (G-CSF) may temporarily create improvement, but neither by itself is a lasting solution. Both are recombinant products, and the human origin may provoke an antibody response. (There are feline-derived versions of these synthetic hormones which have been pegylated for extended bioactivity, but they have to date been judged unprofitable by potential manufacturers and are unavailable for clinical use.) Neupogen, which is largely a stimulant for production of neutrophils, provokes an antibody response around the two-week mark and is only likely to be effective for three to four weeks. It also raises viral loads. However, cats receiving chemotherapy for cancer may have their immune response suppressed to the point where antibody response is retarded. Niacinamide has been shown to stimulate production of native G-CSF. Chemically similar epoetins such as Epogen, Procrit, and Eprex (in Europe) can work considerably longer than Neupogen, and many cats--at least in the short term--do not show antibody response. Dosage of Epogen, for instance, is 100 to 150 units/kg subcutaneously every two to three days. "As it is a human recombinant product, about one fourth to one third of cats receiving this hormone will produce antibodies against it in six to eight weeks." Epoetin, however, has the more potentially dangerous side-effect. Antibody response can cause a fatally refractory aplastic anemia. Moreover, "Care must be taken against overzealous use of this product, which can lead to polycythemia with severe to fatal results. As the Hct reaches the reference level, the interval dosage of erythropoietin is reduced to every fourth or fifth day" [Bernard Feldman, Feline Anemia: Practical Investigation and Management]. Aranesp, a darbepoetin similar to epoetin but with additional carbohydrate chains, is believed to be somewhat less susceptable to antibody reactions and has the advantage of a longer half-life so that the period between dosings is extended. However, it works somewhat less quickly than epoetin and is somewhat more expensive. Contrary to some veterinary opinion, epoetin and darbepoetin can be helpful in situations other than kidney failure. In human medicine they are used routinely to treat HIV- related and cancer-related (and chemotherapy-related) anemia. In HIV medicine, they are regarded as preferable to transfusion, which has been linked to worsening disease. Epoetin/darbepoetin and Neupogen can be used concurrently. Because of possible side effects, epoetin and darbepoetin should be used by cats only when anemia reaches a serious level and is not expected to improve. Lactoferrin effectively complements epoetin or darbepoetin at least as well as oral and i.v. iron supplementation without contributing to iron overload. Levamisole is likewise a short-term solution, potentiating the cell-mediated ( TH1 lymphocytic) immune response, but acting immunosuppressively over time. Lymphocyte T Cell Immunomodulator (LTCI) is reported to be broadly hematopoeic, spurring production of red cells as well as of major white cell groups (probably through indirect stimulation of Interleuken-3 production). It may be an important new weapon in the arsenal directed at cytopenias.
5. Maternally Derived Infection
I am aware of no studies either of mortality or of therapeutic agents in cats infected at birth, as a distinct population. It has been established, though, that infected neonates seem generally to experience an accelerated disease process and, on average, die younger than other cats. Because most people with FIV+ cats do not know when or under what circumstances their cat was infected, some guesswork is often involved. But it is not at all uncommon to see maternally infected cats developing FIV-characteristic pathologies in their first year. My own observation is that a fair number of such cats
do not live past two or three years of age; those who do often show evidence of decline at the six-to-eight year period. Some, for whatever reason, go on indefintely with few problems, though, on average, these are a smaller percentage than cats infected when mature.
If I had an asymptomatic kitten that tested FIV+, if the positive status were reliably confirmed, and if I were determined to do everything possible to insure survival as long as possible, then I would begin immediately treating the kitten by incorporating some of the elements of treatment for an ARC-stage cat into its therapeutic program. If I had a symptomatic cat that I had strong reason to believe was maternally infected, I would treat it as an AIDS-stage cat. Having said that, I will confess, as well, that I do not know how effective dramatic interventions would be, or whether they would justify the effort and expense put into them. Dosage adjustments may be needed for some supplements if given to a kitten.
Oral Alpha or Omega Interferon (preferably Natural Alpha)
B Vitamin Complex
L-Carnitine or Acetyl-L-Carnitine
Vitamin B12 & Niacinamide
Alpha Lipoic Acid or Co Q10
Selections from both of the above Menus (especially Thymus Peptides and Transfer Factors)
Injectable Feline Omega Interferon if Oral Natural Alpha has already been tried
Lymphocyte T Cell Immunomodulator (Thymic Protein A)
ARC/AIDS-Stage Herbal Regimen (especially Olive Leaf and Prunella)
1. Some form of interferon treatment could begin immediately, even in an asymptomatic cat. Beginning with oral Alpha or Omega Interferon is prudent. It costs less than injectable Feline Omega, is less intrusive to give, and leaves open the option of Feline Omega (or some other immune stimulator or modulator) if later circumstances appear to warrant it.
2. Much of the explanation for the poor prognosis for maternally infected cats is thymic damage
that stunts development of a mature immune system. Thymus Peptides may or may not improve the situation, but there always the chance that they can help compensate for impaired thymic function, especially as regards outfitting cytotoxic (CD8+) T lymphocytes, which are crucial to control of FIV infection. More than any cat, maternally infected cats should have this supplement. The new product Lymphocyte T Cell Immunomodulator (LTCI) might be made to order for maternally infected cats showing disease symptoms. Although research has not established whether LTIC can be used effectively in concert with interferon, anecdotal evidence suggests that it can. The expense would be formidable. Melatonin has also shown regenerative action on thymic tissue and stimulative action on thymic hormones. It could be used alternately or concurrently with thymus peptides.
3. Herbal supplements might prove a chore getting into a rambunctious young cat, but those least likely to cause problems if given long term are a potential weapon in the arsenal. It is possible that herbs given with a lipid and an emulsifier would more readily enter the lymphatic system (that includes the thymus) than those given with piperine.
4. Transfer Factors are made up of small amino acid chains, particularly of proline, and are therefore referred to in scientific literature as PRPs, or Proline Rich Polypeptides. Transfer factors are passed on to newborns in colostrum to provide passive immunity early in life by “educating” the immune response in ways that are not yet clearly understood, but that seem to
involve the selective production of host “cytokines” (immunoregulatory proteins) and the stimulation in the thymus of T-cell differentiation with a TH-1 bias. There is some research suggesting that transfer factors engineered to be specific to the diseases for which they are being given (including HIV) have some beneficial effects. Some research indicates that PRPs are not species specific and that those derived, for example, from cows and sheep, are effective in other species and actually have greater resistance to degradation in the digestive tract than many host-derived PRPs. Where transfer factors are concerned, it is not always easy to separate the science from the pseudoscience. Research seems to show that different cytokines are stimulated by different disease organisms. It remains to be seen whether FIV evokes a favorable cytokine response, although it is quite possible bovine PRPs are therapeutically useful for other diseases made possible by FIV. Since transfer factors are intended by nature for newborns, this is certainly a situation in which their use is defensible.
5. A symptomatic cat who has been maternally infected is on a slippery slope to rapid deterioration, much more so than a symptomatic cat otherwise infected. Whether HIV antivirals would have the same expected impact on the former as on the latter I simply don’t know. Even if they did, they would only work for a time, but possibly time to gain traction to move on
eventually to other therapies. For someone willing to try anything, this is an available option.
6. Checklist: Choosing Among Therapeutic Agents
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