Bud’s Medications and Supplements
1. Introduction
2. HIV Drugs
3. FIV Botanicals
4. Immunostimulators and Immunomodulators
5. Wasting
1. Introduction
Standard veterinary medicine’s approach to FIV infection is to “play defense”: to treat the
diseases it causes, but to largely ignore the virus and the immune system it attacks. Such a strategy
would be unthinkable today for humans infected with HIV. Even casual research, however, will
show the cat owner in search of a better strategy that therapy for cats suffering from FIV is
largely off the radar and left to guesswork by individual veterinarians, a shocking number of
whom counsel euthanasia.
Your veterinarian has had very little guidance in treating FIV apart from “playing
defense” and likely will not have the time or inclination to research experimental therapies.
It is very helpful to find a vet who is open-minded and cooperative. But don’t expect much encouragement. Vets will tell you that little has been "proven" to be of benefit, although this is generally a view accepted as received wisdom, not through actual research. Those who style themselves authorities and pass on this view set the bar impossibly high by pointing to an absence of long-term studies that are never likely to exist unless supported and funded by a marketer looking to make money. This unfortunate reality takes most supplements off the table and limits research in pharmaceuticals to multi-purpose agents. There is limited money to be made from targeting a disease largely limited to rescued stray cats.
So here is the primary lesson for the person who wants to aggressively fight his cat’s FIV
infection: Learn to do your own heavy lifting. I did and was fortunate to make contact
early on with some people who felt the same and who were helpful to me in both research and
suggestions for practical therapies. With so little research available on FIV therapy, I have concentrated on uncovering therapies researched for the treatment of HIV. However, where in vitro and in vivo research on FIV therapies exists, I have noted and described it. Because most of
the medications and supplements described here have been applied experimentally, anyone who attempts to duplicate any part of this therapy does so at his or her own risk. What helps one
cat might not help another–might even do harm. That a therapy has worked to a medical
certainty is not always easy to measure in individual cases; a variety of causes might account for
some positive development in a cat’s health. I have italicized any therapy that I have not tried on
my own cat and then gone on to explain who has. I have also listed dosages I used, but dosages
for cats of medications and supplements not ordinarily given to or extensively tested on cats are
guesswork Only a number of pet owners cautiously “pushing the envelope” will establish
optimal dosage.
“Bud’s FIV Therapy” was not a program of FIV therapy. It was very much a matter of learning
as one goes. What I would have done had Bud his life to live over again may be seen on the page
of this site entitled Bud’s “Second Chance”: Lifetime FIV Therapy. Since the content of this
site is constantly being updated to reflect newly discovered research, those taking away
information should check back periodically for updating and assurance of continuing validity.
2. HIV Drugs
HIV antiviral drugs work on FIV as they do on HIV to reduce the number of infecting viruses,
not to eliminate the virus entirely. Unfortunately, available drugs in only one class (see *Notes later) of HIV
antivirals–the nucleoside reverse transcriptase inhibitors, or NRTIs (often called Nukes)–have so
far (with one recent exception) proven to be effective against FIV, albeit to a lesser degree than against HIV. (Reverse transcriptase is the enzyme used by FIV and HIV to translate their RNA into DNA for integrating
into the host genes.) At least five drugs within this class can be given to cats with few or
manageable side-effects. (That number may grow if claims about a supplement that maintains
levels of a nucleoside called uridine prove true and applicable to cats. Side-effects of some
NRTIs have been linked to a phenomenon called “mitochondrial toxicity” in which uridine is a
key player.) These drugs will only be effective for a time, and all NRTIs do carry varying risks
of certain serious side effects: anemia, pancreatitis, peripheral neuropathy, and hepatomegaly
(i.e., liver enlargement). These are generally effects of long term use. Bud did not experience
these or any other side effects, nor did Poose, the cat belonging to Martina Menz, whose example
and advice were so crucial in helping me to decide to treat Bud with NRTIs. Dosage per body
weight generally reflects that which would apply to babies or very small children. Dividing a
cat’s weight by an “average” human weight and downsizing the adult human dosage accordingly
is another approach, but may yield too conservative a dosage because of the higher feline
metabolism.
● Abacavir (ABC). Among the newer RTIs, ABC may carry with it a small (4-5%) risk of
serious sensitivity response: nausea, vomiting, diarrhea, cough, breathing difficulties.
Fever almost always accompanies a reaction, which usually occurs within the first six
weeks of administration. The drug must be permanently discontinued if a reaction is
suspected. Continuing or “trying again later” can have grave consequences. (This
reaction has been linked to a specific gene present in susceptible humans, so it is unclear
whether felines are liable to it.) Otherwise, the drug has comparatively few side effects
and has the advantage of being able to suppress viral replication in the central nervous
system. Half dosage when there is preexisting liver disease. (Bud's Dosage: 30mg twice daily;
7.5mg/kg of body weight)
● Lamivudine (3TC). 3TC has never been recommended as monotherapy (i.e., given
alone) because resistance sets in within a matter of weeks. It is a good choice, however,
for multiple drug combinations, where the partner drug(s) can select for its characteristic
mutation. A suspect study of the AZT/3TC combination in FIV-infected cats showed a
puzzling lack of reduction in viral load–puzzling because other studies have shown
clinical benefit in AZT alone, and 3TC would be expected to add synergy. Recent HIV
research suggests that the lamivudine might even be beneficial as monotherapy to the
extent that its characteristic mutation produces a less hardy virus. Comparatively few
side effects. Half dosage when there is preexisting kidney disease. (Bud's Dosage: 15mg twice daily;
3.75mg/kg )
● Tenofovir (TDF, formerly PMPA). A new drug that can be given in relatively high doses because of
good tolerance and few side effects. Recently, there have been some reports by HIV
researchers of kidney damage (renal tubular injury) associated with medium to long-term
use, though this occurrence is still described as “rare.” (Low body weight and preexisting
renal impairment are risk factors.) Monitoring of blood values associated with kidney
dysfunction is wise, because problems do seem reversible with discontinuation.
Technically a nucleotide (not nucleoside) because its chemistry allows it to skip a step
(“phosphorylation”) in becoming RT inhibitory. Also stimulates interferon production.
(Bud's Dosage: 50mg once daily with a meal; 12.5mg/kg)
● Emtricitabine (FTC). Chemically similar to 3TC, FTC, a newer drug, produced less
impressive results in preliminary head-to-head testing for viral load and T-Cell counts (T-Lymphocyte loss is the primary disease-disposing result of FIV infection); however, drug
resistance sets in less quickly than with 3TC. Side effects and restrictions similar to those
with 3TC. (Bud's Dosage: 22mg once daily; 5.5mg/kg) Note: FTC and 3TC should not be used concurrently in a multi-drug regimen.
Development of resistance to one precludes use of the other.
● Didanosine (ddI). An English cat owner, John Finlow (contact me for information
regarding his e book) treated his cat for over a year with ddI. DdI carries with it more
risk of the nucleoside-characteristic side effects, most notably pancreatitis; GI side
effects are not uncommon. In HIV therapy sometimes potentiated with a drug called
hydroxyurea (HU). This potentiation has also been shown with tenofovir, though to a lesser extent. One research source suggests that HU does not inhibit FIV replication,
although Finlow is convinced it was effective. It has been shown that HU inhibits HIV replication in monocyte-derived macrophages and dendritic cells at concentrations which are insufficient for inhibition in activated T cells. It is possible, therefore, that concentrations were insufficient for the T cell lines used in the FIV study. Other recent research indicates that the antioxidative supplement Resveratrol adds synergy to NRTIs such as
ddI without the side effects of HU. (Finlow specifies a dosage of 10mg for a 3kg cat,
using only the 100 mg tab; given twice daily, one to two hours before meals; buffering
creates restrictions for co-administration with some drugs because of possible
interactions.)
● Zidovudine (AZT/ZDV). Although the only HIV drug approved for FIV therapy by Kirk’s Current Veterinary Therapies, 13th ed, AZT is not a desirable first-use drug for cats. Anemia generally sets in within weeks. If a cat does not subsequently adjust to the drug, it must be discontinued until the hematocrit (red blood cell density per unit volume) returns to a normal range. One study has claimed long-term clinical benefit for such a “pulsed” therapy. Standard dosage is 5mg/kg twice
daily. NucleomaxX, a supplement rich in nucleosides, has shown some early potential
for solving the problem of this anemia, though it has not, to my knowledge, been tried on
cats and is bitter tasting. For a cat who has already used other NRTIs to the point where
the virus has overcome them, however, AZT offers the best chance as a “next choice,”
being the least cross-resistant among the available alternatives.
Drug Regimens: Three-drug minimum combination therapy (called HAART, for Highly
Advanced Antiretroviral Therapy) is standard today in treating HIV, producing the best viral
suppression and the longest time without drug resistance setting in, and involves the combining
of antiretroviral drugs from at least two classes: NRTIs, NNRTIs (nonnucleoside reverse
transcriptase inhibitors), protease inhibitors, integrase inhibitors, fusion inhibitors, and coreceptor inhibitors. The last four inhibit viral replication at different stages of the viral replication process from NRTIs and
NNRTIs. In trials, various three-drug combinations containing only NRTIs have shown less
impressive results than combinations mixing NRTIs with at least one drug from another class. It
is likely (but unproven) that the same is the case with FIV. Bud’s regimen was first TDF (PMPA) +
ABC + 3TC, then became TDF + ABC + FTC. Giving a single drug or a two-drug
combination are certainly options; a two-drug combination might even be preferable to a three-drug combination, although a three-drug combination that contains AZT and that, by some
means, can be given continuously may prove the best (see “Outcomes”). Completing a two-drug combination with a herb or herbal combination with activity beyond RT inhibition is a possibility. A recent HIV study of two NRTIs + selected herbs found greater viral inhibition when compared to the two NRTIs alone and found an increase in T cells missing with the two NRTIs alone. The International AIDS Society-USA guidelines recommend both tenofovir/emtricitabine and abacavir/lamivudine as preferred NRTI options for use as components of first-time HIV therapy because of their effectiveness and relative paucity of side effects. Double combination therapy with TDF and 3TC was done by Marcel Blanc in France. The double-combination did
not outperform Bud’s triple-combination. (See Appendices: Reports . . .) TDF and ddI should
not be given together in any combination, however, because they interact, raising the level of ddI
intracellularly. Prudence dictates initiating any drug combination one at a time in order to be
able to attribute short-term side effects to their proper source. Bud took TDF first; 3TC a week
later, and ABC 7 weeks later (because of an attack of hepatitis at the time therapy was begun).
*Note. Raltegravir, an HIV integrase inhibitor, has recently become available. (Integrase
is the enzyme in HIV and FIV that facilitates integration of viral RNA into human or
feline DNA.) Raltegravir has not, evidently, been tested on FIV, but might be effective. A
sister drug with a similar chemistry, designated L-870,810, has been shown to be a
significant FIV integrase inhibitor. However, it is no longer in development.
*Note. Mozobil (plerixofor), a version of the bicyclam fusion inhibitor AMD3100, is
currently in trials as a cancer drug and may become clinically available. AMD3100,
which inhibits a host chemokine necessary for viral fusion with the target cell, was
largely abandoned as an HIV drug, but in a six-week trial on FIV+ cats showed
significant beneficial action without side effects.
*Note. Tipranavir, a recently approved HIV protease inhibitor, has been found to inhibit FIV with similar efficiency and to interact synergistically with the PI “booster” drug Ritonavir against FIV. Although possible side effects in cats have not yet been
assessed, multi-class HAART therapy for FIV is now at least theoretically possible.
>>>OUTCOMES: HIV Drugs>>>
3. FIV Botanicals
Some readily available botanical supplements have shown an ability to suppress HIV replication
in vitro (i.e., in a culturing medium); a few have been tested in vivo. It is unknown whether this
ability extends to FIV or whether, in every case, oral administration produces a similar result.
One approach to combination therapy with botanicals showing action against HIV is to target
several points of the viral replication cycle, just as HAART therapy with HIV drugs seeks to do.
Caution should be exercised in giving herbal or other supplements to cats simply because they
have proven harmless to humans. Supplements sometimes have “multiplier” effects when given
with other supplements. Cyclical administration may mute possible long term side effects and
limit time of co-administration with supplements that may produce multiplier effects. Bud never
used all of these supplements concurrently. Allison Berneck did five-herb combination therapy
(the five that first achieved undetectability in Bud) on her cat RPM. (See Appendices: Reports . .
.)
● Chrysin. A potent anti-inflammatory agent extracted from a species of passion flower, chrysin binds to a cellular enzyme (Casein Kinase II) necessary to phosphorylation of HIV reverse transcriptase and protease and of viral and host transactivating proteins. ( Transactivation accelerates replicating
activity of provirus embedded in host DNA.) Because of poor absorption, requires an
accompanying delivery agent to insure bioavailability. (See the Note at the end of this
section.) Chrysin is often sold with an activating additive called LPC, about whose safety
doubts have been expressed. An alternative delivery agency is piperine (black pepper
extract) and zinc. In humans, the proportions are 500mg chrysin + 5mg piperine +10mg
zinc. No report of significant side-effects of chrysin at normal dosage levels.
(Bud’s Dosage: 166mg chrysin + 2mg piperine + 1.25mg zinc monomethionine twice
daily) Note: Chrysin also may have weight gain benefit in an unneutered animal. It prevents the conversion of testosterone to estrogen and is used by some body builders as
part of a bulking regimen. Piperine can be bought under the brand name Bioperine.
● Glycyrrhizinate (from Licorice). Glycyrrhizin, a component of licorice root, inhibits viral adsorption, or
binding, and may have some activity against other viral elements via CKII inhibition.
Favorably affects CD4+ cell counts and CD4: CD8 ratio (benchmarks of
immunosuppression) and inhibits cell-to-cell infectivity and syncytium formation
(clumping of infected CD4+ cells). One study showed glycyrrhizin slowing disease
progression in asymptomatic HIV patients. Glycyrrhizinate is a proprietary licorice root
compound (marketed by Jarrow as Glycyrrhizinate Forte, but now discontinued), containing 25% glycyrrhetinic
acid and 25% monoammonium glycyrrhizinate. Possible dosage-mediated side effects
include low potassium and high blood pressure resulting from inhibition of conversion of
cortisol to cortisone. Added glycine in Jarrow product (and Japanese pharmaceutical
Glycyron) helps prevent side effects on sodium-potassium balance; added L-methionine
helps efficient delivery of detoxifying cysteine to liver. Glycyrrhizin compounds are preferable to licorice since other components of licorice lower serum levels of glycyrrhizin. Licorice a traditional tonic for the
liver with some steroidal-like anti-inflammatory qualities, but contraindicated where there
is preexisting kidney disease, heart disease, or cirrhosis of the liver. Monitoring for side
effects is prudent. Deglycyrrhizinated licorice root does not have potential side
effects, but is not antiretroviral. Arthur Gittleman,
who has generously passed on research and suggestions, gave glycyrrhizinate to both
of his cats for many years without side effects. (Bud’s Dosage: 60mg twice daily,
raised to 75mg; first round, 60mg once daily) Contact me for information on replicating
the discontinued Jarrow formula. Read more . . .
● Olive Leaf Extract (OLE). Although no research appears to have been done to date of
olive leaf extract as an FIV therapy, research as an HIV therapy has been so promising
that a number of researchers have pointed to the possibility of creating new HIV drugs
based on synthetic derivatives. Olive leaf has been widely touted for some time as a
reverse transcriptase inhibitor. This view has uncertain origins and seems to be rooted
in a 1998 study on natural products that inhibit RT. However, more recent studies have
identify oleuropein, the chief active constituent of OLE, and its metabolite
hydroxytyrosol, as HIV inhibitors at both the fusion and integration stages, the former by
binding the viral envelope protein responsible for fusion and the latter by inhibition of the
viral enzyme integrase at three separate points of activity. Whether these recent findings
supercede the claim of RT inhibition is unclear. The same study team has demonstrated
that oleuropein is a potent inhibitor of both free viral and cell-to-cell transmission of HIV;
that it restores patterns of cellular signaling; and that it upregulates proteins that inhibit
"apoptosis" (cellular self-destruction) caused by viral exposure. OLE does not interact
with RT inhibitors drugs commonly used to treat HIV, and, like resveratrol, displays synergy with AZT and
particularly with 3TC. Contradictory anecdotal claims by users that viral mutation does
or does not overcome OLE within several months when used as monotherapy. Has many
other potentially useful properties. It is a potent antioxidant that placed second only to
resveratrol, the antioxidant in the skin of red grapes, in a recent trial. Also a natural
antibiotic, with documented action against many bacteria and fungi. OLE is available as
a veterinary product under several trade names. Any product used should be standardized
to no less than 15% oleuropein. No significant side effects have been reported in cats.
However, some sources advise of a possible short-term “detoxing” effect (a Herxheimer
reaction) in humans, involving fatigue, aches, possible diarrhea, due to an accumulation
of waste products in the lymphatic system (Bud’s Dosage: 267mg twice daily, raised from
125mg) Read more . . .
● Curcumin. The principle component of turmeric (curcuma longa). A number of in vitro
studies have shown curcumin to be a moderate antagonist at several points of the HIV
replication cycle, inhibiting the viral enzymes protease and integrase, as well as the LTR
(Long Terminal Repeat), the viral On-Off Switch. Also downregulates CXCR4, the host
chemokine co-receptor recruited by FIV to complete viral fusion with target cells.
Curcumin has strong anti-inflammatory qualities through suppression of inflammatory
signaling proteins (“cytokines”) TNF-α and Interleuken (IL)-1β and the antibody-inducing cytokine IL-6; however it also inhibits synthesis of IL-2 (necessary to activation
and expansion of CD4+ T cells), suppresses IL-12 ( a co-stimulatory molecule, along
with IL-2, necessary to CD8+ cell activation), and upregulates IL-4 and IL-10, both
inducing antibody, not T cell immune response. (See following sections on
“Immunomodulators” and “Wasting.”) Unclear whether this is a desirable agent for FIV, although the weight of evidence suggests that it is. A study of usefulness for HIV-associated diarrhea, for instance, found no loss of CD4+ cells and no interaction with HIV drugs.
Because of poor bioavailability, should be taken with a delivery agent such as piperine or
lecithin. No significant short-term side-effects, though some concern has been expressed
about possible gastritis or stomach ulcers if taken long term at high dosage. Because it
stimulates bile flow, contraindicated if there is bile duct blockage or gall stones. Should
be taken with food. to minimize irritation. One source places a therapeutic feline dose of
curcumin at 50-100mg daily and cites 100mg/kg as a benchmark ulcerogenic dose in
“animals.” One cat owner recently reported giving daily dosages as high as 1 to 1 1/2 grams. (Human dosage: 2000mg curcumin, 20mg piperine, divided three times daily;
Bud’s Dosage: 225mg curcumin, 6mg piperine, divided three times daily between meals;
second round, 200mg with piperine and 50 GDU bromelain, divided twice daily with
meals)
Read more . . .
● SPV-30. Extracted from boxwood by a proprietary process, SPV-30 (now marketed as
Flu Guard) during the mid-nineties was part of a favorite herbal cocktail in the AIDS
underground, along with curcumin, licorice, and bitter melon. Clinical trials in France
and later tests in the U.S. aided by the manufacturer at the behest of independent parties
showed significant reductions in viral load, particularly among those with a viral load
higher than 40,000, although 1997 and 1998 trials by the same party returned somewhat contradictory data. Dosage is important, since in trials too much produced the same
effect as none. Unfortunately, dosage for cats is guesswork. Red flag is that the
manufacturer did not seek to replicate the data for formal FDA testing, although meeting
FDA standards can be prohibitively costly. FDA ordered maker not to advertise as an
HIV-specific drug. May target viral reverse transcriptase and has anti-inflammatory
(downregulating TNF-α, a proinflammatory cellular factor) qualities. Because boxwood
contains plant steroidal triterpenoid alkaloids, some sources have advised
caution or avoidance due to possible long-term immunosuppression and/or liver toxicity,
although previously cited studies did not report evidence of these problems. A recent pharmacological study found suppression of Interleuken-2, the primary T-cell growth factor. It is unclear whether this is a desirable agent for FIV, particularly in a cat already highly immunosuppressed. According to one botanical source, the living boxwood plant may be toxic to cats, although nothing in Bud’s experience validated this view and the manufacturer is unaware of animal toxicities. Occasional GI side effects reported in human use. (Bud’s Dosage: 82.5mg three times
daily)
● Prunella Vulgaris. A traditional Chinese herb, also called All Heal, Heal All, and Self
Heal. A strong HIV fusion inhibitor through disruption of the HIV-gp41 six-helix bundle formation, a critical step of membrane fusion between the HIV, and the target cell and through possible CXCR4 co-receptor inhibition. Also a moderate inhibitor of the HIV enzymes protease, integrase, and reverse
transcriptase. No side effects reported. However, since prunella is rich in tannins (the
source of its antiviral actions), a cat with kidney inflammation should probably not be
given it. Chiefly available as a liquid alcohol-containing extract, although at least one capsulized extract is now available. Also a proven inhibitor of human herpesvirus-1 (oral) and herpesvirus-2 (genital), and therefore a likely inhibitor of feline herpesvirus. (Bud’s Dosage: 8-10 drops twice daily) Contact me for information on obtaining the capsulized extract.
● Bitter Melon. An extract of the plant momordica charantia . Active agents are a series
of proteins designated alpha and beta momorcharins and a protein called MAP30.
Collectively, these have shown several types of inhibitory activity against HIV: viral
integrase inhibition, interaction with viral LTR, and inactivation of ribosomes that
process viral mRNA. Fruit liquid drunk as a tonic in some parts of the world. Used
experimentally as a veterinary drug with dogs to control diabetes. Because of insulin-like
properties, bitter melon should not used by diabetic cats taking insulin. Some
reservations have been expressed about possible hepatotoxicity with long term use.
Because of influence on sugar metabolism, term-limited usage might be wise. May
deplete potassium, and probably should not be used for long with other products that may
deplete potassium, such as licorice or green tea. The product used claims to contain 15%
charantin. (Bud’s Dosage: 250mg, divided three times daily, raised from 150mg; dosage
in dog studies 300-600mg daily)
● Green Tea. An extract of the plant camellia sinensis. Active agents are a group of
bioflavonoids called catechins. Epigallo-catechin-3-gallate (EGCG), the principal
component of the group, is a reverse transcriptase inhibitor and also a fusion antagonist,
binding the main FIV chemokine receptor CXCR4. Green tea extract has been characterized as a
potent antioxidant and suppresses TNF-α, a proinflammatory cellular factor. However, green tea does upregulate antibody response, and suppresses the TH1 cytokine interferon-γ (maybe good, maybe not), and so probably should not be paired with other agents with a TH2 bias. Mature dendritic cells (which activate T cells) treated with EGCG inhibited stimulatory activity, a potentially troubling finding. Recent reports that large amounts of green tea are hepatotoxic and deplete glutathione and that bodily processes may transform the antioxidant effect in vitro to a prooxidant effect
in vivo. Green tea can deplete potassium by the same route as licorice and should not be
used for any length of time with licorice or with other supplements that deplete
potassium. It may also contribute to both loss of bone density and iron deficiency if given long term without relief. (Iron supplements should not be given at the same dosing as green tea.) Unclear whether green tea is a desirable FIV therapy. Piperine has been shown to enhance the uptake of EGCG, as it does curcumin. Because caffeine is toxic to cats, the product used was decaffeinated; it claimed to be standardized to 70% EGCG. (Bud’s Dosage: 250mgs, divided twice daily; see Curcumin for piperine and bromelain dosage; piperine should not be used more than twice daily.)
● Grape Seed. Active agents are bioflavonoids called oligomeric proanthocyanidins
(OPCs). Grape seed extract is a potent antioxidant, which, because it crosses the blood-brain barrier, is thought to be a useful neuro-protective agent. OPCs are fusion antagonists, inhibiting the chemokines CCR3 and CCR5, which are secondary FIV co-receptors in some strains that enable expression of the primary co-receptor CXCR4. For this reason, green tea or curcumin and grape seed may be a natural pairing. OPCs have also been shown to contribute to a TH1 (T cell inducing) cytokine profile. (See sections on “Immunomodulators” and “Wasting”). Grape seed has shown significant activity against soft tissue (breast) and skin tumors, as well as leukemia. The product used is called a “phytosome” form of grape seed, in which binding to phosphatidylcholine is said to increase bioavailability.
(Bud’s Dosage: 25mg twice daily)
● Other Supplements. Given at various times: Zinc (2-4mg twice daily); Vitamin C
(125mg twice daily with non-acidic Ester-C); Denosyl/SamE (90mg daily); N-Acetylcysteine (NAC) (150mg daily); Vitamin E (400 I.U. twice weekly, lowered to 100
I.U.)*; Alpha Lipoic Acid (25mg daily, lowered to 17mg )* ; L-Glutathione (10-20mg
daily); CoQ 10 (25mg daily); L-Glutamine (125-250mg daily);L-Carnitine/Acetyl-L-Carnitine (250mg daily); [Neural Protective] MethylB12 (.5mg daily). Supplements known to
enhance liver function–Denosyl/SamE, licorice, curcumin–may act as a hedge against
others which are liver stressors. Periodic “holidays” in which these
(“other”)supplements are suspended are perfectly acceptable, even desirable, though a
“rolling” schedule is also desirable so that a variety of supplements are being given at
any one time. For more information on uses of these supplements, see “Bud’s
Therapeutic Guidelines.” * [According to one source (actually a footnote citing unpublished research) dosages of Alpha Lipoic Acid in excess of 25mg can be neurotoxic in cats. Although it is possible that this was a misprint for 25mg/kg , a dosage below 25mg would be prudent. Another study reports greater liver sensitivity to ALA in felines compared to humans, rats, and dogs. Hepatotoxicity level set at <30 mg/kg of body weight. A recent metastudy of Vitamen E in humans concluded that large dosages are statistically associated with poorer outcomes in areas unrelated to the known benefits with retroviral infections.]
Note on Bioavailability: A number of herbal extracts, particularly polyphenols, are poorly absorbed in the intestines and require some kind of strategy to improve absorption and maximize serum concentrations. Co-administration with piperine is one. Piperine increases absorption from the gut and inhibits enzymes that cause biotransformation and inactivation of drugs and supplements. A fundamentally different approach is administration as part of a lipid emulsion. Lipids are taken up directly into the the lymphatic system via lacteals and gain a “first pass” of the liver, where the agent contained within them might be degraded or metabolized to an ineffective form. One method, for instance, involves mixing an extract with a lipid (e.g., oil), an emulsifying agent such as casein (fairly easy to come by), and a minimal amount of food, such as baby food. “Phytosome” products (called liposomes) take advantage of the special lipid properties of phosphatidylcholine, or lecithin. When the herbal component is combined with the phosphatidylcholine, the choline head binds the component, while the fat-soluble phosphatidyl portion envelopes the choline-bound material. The resulting phytosome is protected from destruction by digestive secretions and gut bacteria. At the same time, absorption and biological activity are improved.
Note on Antioxidants: The value and appropriate dosages of antioxidants are a subject of
ongoing scientific study and are emphatically not a settled matter. Many antioxidants are
believed to become prooxidant under certain circumstances and at certain dosage levels for
certain periods of administration. In numerous cases, contradictory evidence has emerged from
studies, indicating that while a certain antioxidant may have benefits in one area, there may be
an increase of risk in another.
>>>OUTCOMES: FIV Botanicals>>>
4. Immunostimulators and Immunomodulators
Cats suffering effects of FIV do not suddenly get well when placed on antiviral regimens. Some
of the damage to the immune system can probably never be undone. However, several
medications and supplements might strengthen the immune system when used either with or
without concurrent antiviral therapy. It is important, however, to try to strengthen immunity
without either increasing viral load or provoking an even greater proinflammatory tilt to an
immune system already pushed in that direction by the action of the virus.
● Immunoregulin. An intravenously injectable preparation of inactivated bacteria
(propionbacterium acnes) designed to provoke and sustain immune response. Anecdotal
reports suggest that it is useful when given intensively to help an animal deal with an
overwhelming secondary infection; the worth of maintenance regimens (injections every
3-4 weeks) has not been established. Immunoregulin activates macrophages, increases
natural killer cell activity, and enhances cell-mediated immunity generally. White cell
counts will likely rise, but activation of lymphocytes may leave them vulnerable to the
FIV, resulting in higher viral loads. Research will need to clarify this point. (According to
communication from the manufacturer in January 2004, research was in progress at that
time. The lack of any word on the subject since then may be significant.) Where white
cell deficits or poor reactivity present a near-term threat, the upside may outweigh the
downside. Literature is lacking on ImmunoRegulin’s effect on the proinflammatory tilt
characteristic of FIV infection. Minor short-term side effects following injection may
occur occasionally, but I am unaware of documented long-term side effects. (Bud’s
Dosage: .5ml IV, injections twice weekly for the first two weeks, then once every three
weeks. Stopped, with some overlap, after beginning antiviral drugs) For case histories and testimonials relating to Immunoregulin, contact me.
Note: Baypamun is an injectable preparation of inactivated parapox virus, developed by
Bayer and used, particularly in Europe, to treat FeLV, although one major study was
unable to confirm reports of benefit in earlier studies. Another study did find benefit for
treatment of feline calicivirus. There are no studies of Baypamun as an FIV therapy,
although it is sometimes used for that purpose. Baypamun is a “paramune” modulator. It
activates phagocytosis and NK cells of the nonspecific immune system, not the specific
immune system, which is generally targeted by HIV and FIV therapy, since T lymphocytes
are the most significant target of these viruses. There are claims that Baypamun is of
systemic benefit, stimulating production by cells of the nonspecific immune system of
immune-signaling proteins (“cytokines”) such as interferon alpha and gamma,
interleukens 1, 2 and 12, colony stimulating factors, and tumor necrosis factor (TNF-α),
all important to functioning of specific immunity, but not all necessarily desirable as FIV-therapy. (Dosage: 1ml IM, 2-3 injections 24-48 hrs apart, then weekly)
Note: Acemannan, a polysaccharide derived from the aloe vera plant and studied in FIV+ cats during the early 1990s, has shown similar immune-system responses, activating
macrophages and enhancing cell-mediated immunity. It also has antiviral activity via
inhibition of viral sugar metabolism. As with ImmunoRegulin, data is lacking on long-term survival benefit and influence on proinflammatory tilt of immune system. Form for
oral administration said to be unavailable, although many aloe-containing oral products
are. (Dosage: weekly injections sub-q, 2mg/kg-1)
● Thymus Peptides. The thymus is “home” to the T lymphocytes attacked by FIV and is damaged in the early stages of FIV infection. There they are biochemically outfitted for
their functions (hence the “T”) and sent forth. Some research suggests that thymus
peptides may be beneficial in HIV treatment by helping the thymus to enhance the activity
of CD8+ cytotoxic lymphocytes that limit FIV. There have also been claims that they raise
T-Cell counts generally, as well as counts of Natural Killer (NK) cells of the non-specific
immune defense. I am indebted to Martina Menz for bringing some of this research to my
attention. Studies of a variety of oral and injectable thymic products (Thymomodulin, thymic humoral factor (THF), Thymostimulin, Thymopentin, etc.) have generally found that resistance to opportunistic infection is enhanced, and that those in the earlier stages of HIV might be particularly benefited. Absorption from the intestines is not good. The question of whether oral thymus peptides activate the CD4+ lymphocytes targeted by FIV (thus making them vulnerable to attack) and should be administered in the absence of antiviral agents has not been definitively addressed, although one study of Thymomodulin found no enhancement of the urinary levels of neopterin, a marker of T-cell activation. (Bud’s Dosage: Thym-Uvocal, 48mg twice daily)
Note: Lymphocyte T-Cell Immunomodulator received a conditional license by the Center
for Veterinary Biologics (APHIS) in December 2006 as an FeLV/FIV treatment aid.
Marketed by Imulan Inc., Lymphocyte T Cell Immunomodulator (LTCI) is an injectable
product. Imulan has since formed a distribution alliance with ProLabs Inc, which has made LTCI available in the U.S. only through a number of veterinary pharmaceutical suppliers. http://www.prolabsanimalhealth.com. The parent product (which also has a sublingual version) is derived from cloned
thymic stromal cell lines that normally produce it in humans and other animals. The
same drug has been variously called Epithyme and TISF [T Cell Immune Stimulating
Factor]. All are incarnations of a Thymic Protein A isolated and developed by a Dr.
Terry Beardsley in the 1980's. TPA is a peptide that, according to Beardsley and
researchers associated with Imulan, (1) encourages maturing of CD4+ T lymphocytes in
the thymus that might otherwise be inhibited by disease; (2) stimulates production of
Interleuken-2 (IL-2), sometimes called T Cell Growth factor, which "primes" clonal
expansion at sites where they are needed and where they can enable CD8+ cytotoxic
lymphocytes (CTLs) to perform their function of killing infected cells; (3) induces
“apoptosis” (spontaneous cell death) in virally infected cells and reduces viral load; and
(4) is broadly hematopoietic, producing increases in other major cell groups besides
lymphocytes, including red cells and platelets. Several studies in FIV+ cats have shown
clinical benefit for symptomatic cats with significant decline in viral load and increase in bone marrow cell production Suggested treatment protocol is injections weekly.
(1cc subcutaneous) for four weeks, every other week during the second month, and monthly or as needed after that.
● Moducare™. A blend of plant sterols (beta-sitosterols) and sterolins (beta-sitosterol glucosides) developed in South Africa as potential HIV therapy but first tested on cats
with FIV, which registered impressive statistical gains in survival time. Initial studies
showed ability to arrest decline of T Cell (CD4+) and total lymphocytes counts. Also
claims of inhibition of inflammatory cytokines IL-6 and TNF-α, and “normalizing”
balance of Helper T-cell subtypes. (See following section on “Wasting.”)
Later research claimed an increase in “memory” CD4+ lymphocytes (compared to “naive”
CD4+ cells) necessary to effective cytokine expression and effector activity. A 2002
report suggests that with long-term administration, Moducare begins to cause decline in
CD4 and CD8 counts, while spurring a concurrent rise in non-lymphocytic white cells,
though the study claimed favorable clinical outcomes through “reducing the number of
virus-producing cells,” implying that Moducare induces apoptosis in infected
lymphocytes. Unfortunately, all studies have been conducted by those associated with the
product. Unclear whether the “proprietary blend” serves a medical purpose or simply
permitted patenting. Sesame oil is an alternative source of the beta-sitosterol found in
Moducare. No significant side-effects recorded. (Bud’s Dosage: 20.2mg divided twice daily; initial
dosage 10.1mg once daily)
● Melatonin. Melatonin is a hormone produced in the pineal
gland of the brain and elsewhere. It is a potent antioxidant with numerous immune-modulating
properties (including raising IL-12 production), and is particularly notable for its neuro-protective properties. HIV and FIV exist in the central nervous system. The surface
glycoprotein and protease of the viruses are known to induce apoptosis (programmed cell-death) in cells of the nervous system, and oxidative stress plays a documented role, as
well. Melatonin has shown significant action against these processes. Melatonin has also
demonstrated a rejuvenating effect on age-related thymic involution (shrinking) and some peripheral
immune capacity, such as mitogen responsiveness (proliferative capacity) and Natural Killer cell activity.
Because Melatonin is produced within the body and is intimately involved with the sleep
cycle, it should be given only at night. Although Melatonin supplementation has no
known short-term side-effects ( it does interact negatively with some drugs , such as
Zoloft), data is lacking on long-term use. An effect on the body’s own ability to produce
Melatonin is conceivable, and gradually decreasing dosage prior to temporary or permanent cessation is prudent. Where neuronal deficits do not already exist, cyclical administration might be wise. Melatonin has been used to treat feline anxiety disorders and canine alopecia. Effect on estrus cycle of unneutered females is conceivable. One veterinary source sets a feline dosage range of .5-.8 mgs. (Bud’s Dosage: 1mg before bedtime)
● Bovine Lactoferrin. Lactoferrin is an essential part of mammalian immune defense,
maintaining balance by checking inflammatory tendencies within the immune system. Its
name identifies it as an iron-regulating (-ferrin) protein, and its presence in milk (lacto-)
is an indication of its importance to neonates, whose immune response has not yet
matured. Studies in mice have suggested that bovine lactoferrin has a variety of potential
uses for FIV+ cats, including a protective effect against bacterial infections, parasitic
infections (including toxoplasmosis, a serious threat to immune-suppressed cats and
humans), some viral infections (including feline herpesvirus and calicivirus) and various cancers
(including lymphomas). Because of its anti-inflammatory action, it has also been used
topically and by mouth in cats with some success as a stomatitis treatment. Recent
research has discovered its ability to block viral binding to and subsequent infection of
dendritic cells that, in turn, (1) infect the T cells they interface with and (2) induce naive T
cells to adopt the suppressor rather than effector cell phenotype, prematurely shutting
down immune response. Various studies have shown ability to increase T Cell and
Natural Killer (NK) cell counts, and to enhance phagocytic activity of neutrophils needed
to combat bacterial infections. There is contrary evidence regarding efficiency of
absorption in the intestine, although a recent mouse study found uptake to major organs at
full molecular weight. Lactoferrin does stimulate epithelial and lymphoid tissues in the
gut to release immunomodulatory proteins (particularly Interleukin-18), resulting in better
immune-system balance. In vitro studies have also shown inhibition of HIV viral reverse
transcription and fusion/entry and an in vivo study in children with HIV showed a
lowering of viral burden and an increase in CD4+ (Helper-T) lymphocytes. (Bud’s
Dosage: 175mg divided, twice daily) Read more . . .
● Feline Omega Interferon. Interferons are specialized proteins produced by the body to direct the immune response. Type 1 interferons enhance the activity of CD8+
lymphocytes and of NK cells and inhibit overproduction of B cells and antibody synthesis.
They also exert direct antiviral action by stimulating cellular enzymes to inactivate
viral (e.g., herpesvirus and calicivirus) RNA (mRNA); against HIV, this action occurs only in macrophages, not in T-cells. Virbagen Feline Omega interferon , produced from feline cells by recombinant technology, has recently been licensed in Europe for treatment of FeLV and
FIV; however, it is not yet available in the U.S. Word from Virbac, the manufacturer,
projected availability in Canada in May, 2005, in the U.S. “after that.” Neither has
happened to date. It can, however, be procured from abroad for use in the U.S. (The North
American rights to recombinant feline interferon were sold by the Japanese developer,
Toray, to Scherring Plough, not Virbac. For whatever reason, Schering Plough has not
marketed a product.) Several studies have shown substantial improvement in health and
survival rates of FIV+ animals receiving it, though in a recent FIV study, short-term
administration did not improve viral load and produced only modest white cell gains.
Particularly useful in treatment of FIV-related oral inflammation. Most common side
effect is fever spike several hours after injection. Usual protocol for administration is a
series of five daily injections, repeated at day 14 and day 60. In a 2006 update on use for
symptomatic FIV, Virbac recommended monitoring clinical and hematological status after
each group of five injections and stopping therapy in the event of either nonresponse or a
return to normality. For the first time, it also recommended subsequent five-injection
series in the event of relapse. Some people give individual injections as maintenance
every three to four weeks following the end of the 3 x 5 protocol, a practice not endorsed
by the manufacturer. Dosage: 1MU/kg SubQ. Some people give the interferon in a
highly dilute form for mucosal absorption, the method widely used to give alpha
interferon. (Bud’s Dosage: 4 MU in five-injections series, followed by monthly
injections) U.S. procurement information available on request. Read more . . . "Interferons and FIV"
Note: Human Alpha Interferon has been used for viral infections and inflammatory conditions common among cats with FIV. Because high-dose injectable Human Alpha
Interferon (unlike Feline Omega) provokes a foreign-substance immune response in cats,
it quickly loses potency. Oral administration in a highly dilute form is usual, but its
efficacy has not been universally supported. A new Italian study has found clear clinical
benefit and survival value for cats treated with low dose oral huIFN-α. Although viral
load remained unaffected, a strong immunomodulating effect was evident. However, the
study did not make use of the recombinant interferon currently available; it used a mixed
“natural” interferon-a containing multiple molecular subtypes of huIFN-α, instead of only
one, as with the recombinant product. When contacted, the head of the research team
said that he regarded the type of interferon used as integral to the result. Multiferon, the
trade name for a mixed natural huIFN-a product manufactured by Viragen, is made in
Sweden and currently being marketed for human use in other countries. Alfaferone, the
product used in the study, is produced in Italy. A mixed natural interferon-α is available
in the U.S. called Alferon. Informal trials with natural inteferon-α are currently going on
among members of the FIV-HealthScience forum. Reports appear on the “Bud’s
Therapy and Other Cats” page. Procurement and dosage information available on
request. Read more . . . "Interferons and FIV"
● Dimethylglycine (DMG). An amino acid whose beneficial effects through a process
called “methylation” were discovered in the early 1980s. Given as a therapeutic agent to
treat a variety of human and animal diseases and as an anti-fatigue nostrum. Said to enhance
both arms of the immune system–cell-mediated and humoral–by improving oxygen
utilization and binding free radicals, although a 1992 study of healthy cats sgowed no measurable enhancement of specific or nonspecific immunity. Anecdotal reports by HIV users in 1992 cited
significant increases in CD4+ lymphocytes, and studies have shown activation of alpha
interferon to levels in excess of 500% and increases in B and T cell immunity generally.
Oral absorption regarded as clearly superior to swallowing as a method of delivery. B12
and folic acid have been said by one veterinary source to improve methylation. Stimulation
of humoral immune response and of TNF-α upregulation (see “Ketotifen” below)
should be weighed before using. (Dosage in HIV report 800mg, divided 3x daily, taken
sublingually; Bud’s dosage 45-90mg, once or twice daily, squirted in the base of the mouth
for mucosal absorption)
● Ketotifen. (See “Wasting”)
>>>OUTCOMES: Immunostimulators and Immunomodulators>>>
5. Wasting
Progressive weight loss is a possible result of FIV infection, although it appears to occur less
consistently than in HIV infection. The causes are complex and variable. They include suboptimal protein synthesis, fat metabolism, and nutrient absorption in the small bowel, as well as reduced appetite. For discussion and treatment of GI issues leading to weight loss (and not always involving overt diarrhea), click here (“FIV and Chronic Diarrhea”). When infections or parasites are the cause, they must, of course, be addressed. But weight loss due to such agents often is not fully regained even after
the cause has been successfully addressed. Various medications and supplements may be of use
in dealing with different aspects of the wasting process.
● Cyproheptadine. An antihistamine, cyproheptadine is a potent appetite stimulant.
Inappetence is characteristic of advanced FIV infection, and is thought to have a number
of causes. Vets frequently do not suggest giving cyproheptadine even when poor appetite
is cited as a problem. A cat owner might raise the subject if the vet does not. Primary side
effects are depression and inactivity, mild and tolerable in many cats, severe and
intolerable in some. Hyperactivity and anxiety have also been reported as a side effect.
Dosage reduction is recommended with preexisting kidney or liver disease. Some vets
advocate only short term use, although I have found no studies addressing this point. Use trial and error to find lowest effective dose. (Bud’s Dosage: 2mg, twice daily; once daily or half or less dosage twice daily for less pronounced inappetence)
Note: Mirtazapine, a relatively recent entry into the field of appetite stimulants, was developed
for human use as an antidepressant, but is both an appetite stimulant and an anti-emetic
and is therefore particularly useful for cats that are both inappetent and vomiting.
Mirtazapine comes in a regular formula as well as a rapid-dissolving formula. Either may
be used in animals. Cats are given 15mg twice weekly, another advantage.
● Ketotifen. An antihistamine with anti-inflammatory (including in the small bowel) and immunomodulating action similar to but weaker than thalidomide’s,* lowering levels of harmful “cytokines” such as tumor necrosis factor alpha (TNF-α). Cytokines are immunoregulatory proteins whose balance is badly disturbed by HIV infection, leading to
increase of viral load, chronic inflammation of internal tissues, and reduced ability to
synthesize proteins. TH2 cytokines (Interleukin-4, IL-5, IL-6, IL-13, and, particularly in the case of FIV, IL-10) rise as part of virus-driven runaway antibody response, while TH1 cytokines (IL-2, IL-12, and IL-15), whose function is related to cell protection, decline. One difference between HIV and FIV is that FIV does not, evidently, cause decline of the TH1 cytokine interferon-gamma (Inf-γ) and may even stimulate its production. Side effects in humans are
few and mild. A small study found significant weight gain among HIV patients who took
it for that purpose. The weight is often lost if therapy is discontinued. Not distributed by
the manufacturer in the U.S., but unlike thalidomide, obtainable. (Bud’s dosage: .75mg
twice daily after an initial dosage of .50mg twice daily; dosage used in HIV trial 4mg
daily)
Note: Thalidomide is also an antihistamine (notorious several generations ago for producing birth defects when used by pregant women to combat morning sickness) that
has been used by Dr. Diane Addie at the University of Glasgow to treat feline infectious peritonitis and by Dr. Richard Malik in Australia to treat stomatitis. A uniquely potent immunomodulator, which has produced contradictory results
in studies of its action, but which is evidently a significant selective suppressor of TNF-α
and IL-6 and probably has a TH1 cytokine profile. Used to treat HIV-associated wasting.
Thalidomide has always been unavailable for veterinary use in the United States, but
evidently some vets and/or cat owners have done an end run around domestic controls by
importing the drug from abroad. A recent federal edict now pointedly forbids the practice.
(Dosage: 50mg once daily in the evening)
● Anabolic Steroids. Oral and injectable anabolic steroids are commonly used to treat HIV
wasting. Only low dosage oxandrolone is actually approved for that purpose, producing
poor results. Higher dosage oral and injectable anabolic steroids produce impressive
gains. Injectable nandrolone is reputed to have fewest side effects. Cats, however,
tolerate anabolic steroids less well than humans. A cat with liver or kidney problems
probably should not even be considered as a candidate. Even cats who are sound in that
regard have been known to register rising liver enzymes, indicating inflammation. Cyclical
administration (e.g., 3 months on, 3 months off) would probably be necessary.
Nandrolone phenpropionate is said to be more liver-friendly than the more common
nandrolone decanoate, but is more difficult to obtain. (Bud’s dosage: 10 mg nandrolone decanoate IM every two weeks)
Note: Stanozolol (trade name Winstrol) is an FDA approved anabolic steroid for use in cats and dogs. Possible side-effects same as with nandrolone. Available in both oral and injectable forms. (Dosage: .5-2 mg orally bid, 10-25 mg IM weekly or biweekly)
Note: Megestrol is a synthetic progestin (a steroidal female hormone) that has been used to treat HIV-related wasting and is used to treat a variety of reproductive, behavioral, and inflammatory conditions in cats. Has appetite-enhancing qualities as well, although weight gain tends to be almost exclusively fatty tissue rather than lean body mass, as with anabolic steroids. Prolonged use carries a risk of diabetes and other side effects. Oral form preferable to injectable. (Dosage: 2.5mg orally daily for 4-5 days, then once every 3-7 days)
● Amino Acids. Studies of HIV patients have shown that a mix of mildly anabolic amino
acids, L-Glutamine, L-Arginine, and HMB (beta-hydroxy beta-methylbutyrate, a
metabolite of Leucine), acts synergistically to produce significant weight gain by
stimulating the production of growth hormone. Unclear whether these particular amino
acids would act as efficiently in cats as in humans. Healthy kidneys a must. Although
none of these amino acids are contraindicated for liver disease (glutamine is
contraindicated where actual cirrhosis exists), the liver must have the ability to clear
protein, since amino acids count as protein intake. L-Carnitine, which is actually used to treat obesity, is a possible add-in (250mg daily or more), since it has fat-transport and muscle-protective properties (including the heart muscle). Arginine should be dropped from the combination when Lysine supplementation is taking place or when there is reason to suspect infection
with feline herpesvirus, which thrives on Arginine when its ratio to Lysine increases.
Modest regular supplementation with glutamine may be of value for maintaining intestinal
tone and lessening malabsorption, a common problem in HIV and FIV sufferers. (Bud’s Dosage: 300mg
glutamine, 150mg arginine, 62,5 mg HMB, divided, twice daily; dosage for second round,
500mg glutamine, 250mg arginine, 250mg lysine, 100mg HMB, divided, twice daily;
human trial dosage 14gms glutamine, 14gms arginine, 3gms HMB, divided , twice daily)
Note: Recombinant Human Insulin-like Growth Factor (rhIGF-1) has produced thymic regeneration and replenishment of the peripheral T cell pool in FIV+ cats, and is so-recognized by ABCD Guidelines of the European Advisory Board on cat diseases. Unclear whether there would or would not be a neutralizing antibody response to the human origin over time, as occurs with human recombinant G-CSF (Granulocyte-Colony Stimulating Factor/ Neupogen). IGF-1 is an endocrine hormone normally produced in the liver in response to stimulation by growth hormone (GH) secreted by the pituitary. As a therapeutic, rhIGF-1 acts anabolically and has reversed osteoporosis and wasting in elderly, protein-deprived women. Milk protein (casein) and whey protein (a byproduct of cheese production), given both with and without essential amino acid supplementation, have shown an ability to stimulate human IGF-1 production directly; zinc supplements enhance effect.
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>>>OUTCOMES: Wasting>>>
