FIV infected cat management

#Part1Prognosis for FIV-infected cats

ABCD recommends that cats should never be euthanased just because of an FIV positive test result. There have been reports that FIV-infected cats may live as long as uninfected cats (Kohmoto et al. 1998; Addie et al. 2000; Levy et al. 2007). However, FIV-positive cats have a higher chance of developing clinical signs, mainly due to secondary infection, immune-mediated disease or neoplasia [Lutz et al. 1990; Hosie et al. 1989; Lutz et al. 1988b].
The duration of asymptomatic stage varies according to the infecting variant [Pedersen et al. 2001]. Based on experimental studies, cats infected at a younger age are more likely to progress to an immunodeficiency state [George et al. 1993; Podell at al. 1997].

#Part2General management

Isolation

One of the most important preventative health measures is to protect the cat from other infections. In FIV infected cats secondary infections may not only cause clinical signs but may also lead to progression of the FIV infection itself. Confining the cat indoors will help to avoid the risk of acquiring other infections through contact with neighbouring cats – as well as avoiding potential transmission of FIV. In some multi-cat households in which other infectious disease problems are endemic, consideration should be given to isolating FIV infected cats..

Neutering

Asymptomatic FIV infected cats should be neutered. This will help to reduce aggression in male cats and the risk of transmission of infection. It will also help to reduce wandering and contact with neighbouring cats.

Frequent health checks

FIV-infected cats should receive veterinary health checks at least every six months which should include monitoring of their weight. Periodic routine laboratory testing (haematology, biochemistry, urinalysis) should be considered. CD4 and CD8 monitoring to stage FIV infected cats is controversial and is neither generally available nor realistic in most practice situations.
Surgery is generally well tolerated by asymptomatic FIV-infected cats, but perioperative antibiotic administration should be used in all surgeries and dental procedures. FIVinfected cats can be housed in the same ward as other hospitalized patients; they should, however, be housed in individual cages. It should be considered that they may be ABCD Guidelines on Feline Immunodeficiency Virus 11/21 immune-deficient and should be kept away from cats with other infectious diseases. Under no circumstances should they be placed in a "contagious ward" with cats suffering from infections such as viral respiratory disease.

Vaccination of FIV-infected cats

Whether or not FIV-infected cats should receive routine vaccination is a controversial subject. Experimental studies have shown that asymptomatic infected FIV-cats in early stages of infection develop a strong immune response following vaccination indicating that efficacy of vaccines is as good as would be expected in non infected cats. However, it is not known if cats who have progressed to later stages of infection with immunodeficiency develop an adequate response to vaccination.
On the other hand, safety concerns have been raised about vaccination in FIV-infected cats. First, immune stimulation related to the vaccine may lead to progression of FIV infection by altering the balance between immune system and virus. Stimulation of FIVinfected lymphocytes is also known to promote virus production in vitro. In vivo, vaccination of chronically infected FIV-infected cats with a synthetic peptide was associated with a decrease in the CD4/CD8 ratio. The potential benefits and risks of vaccinating FIV-infected cats should be weighed up in individual cats. In elderly indoor cats which have been vaccinated previously, the risk of acquiring infection is very low so booster vaccination is (probably) best avoided. In outdoor cats with risk of exposure to other infections vaccination is strongly advised.
Although there is no scientific evidence that FIV-infected cats are at increased risk from modified life virus vaccines, inactivated vaccines are recommended whenever available as in immune-suppressed cats these vaccines may retain some pathogenic potential and cause clinical disease.

#Part3Supportive Treatment

Appropriate supportive treatment of FIV-infected cats relevant to presenting clinical signs should be instituted as early as possible. If FIV-infected cats are sick, prompt and accurate identification of the secondary illness is essential to allow early therapeutic intervention and a successful outcome of treatment. Therefore, more intensive diagnostic testing should proceed earlier in the course of illness than might be recommended for uninfected cats. Many cats with FIV infection respond as well as uninfected cats to appropriate medications although a longer or more aggressive course of therapy (e.g., antibiotics) may be needed.
Some clinicians report clinical benefits using corticosteroids and other immune suppressive drugs in FIV-infected cats with chronic stomatitis, but their use is controversial because of potential side effects. Griseofulvin has been shown to cause ABCD Guidelines on Feline Immunodeficiency Virus 12/21 bone marrow suppression in FIV-infected cats and should not be used [Shelton et al. 1990]. Filgastrim, granulocyte colony-stimulation factor, G-CSF, a cytokine that is on the market as recombinant human product (rHuG-CSF), have been used in FIV-infected cats with profound neutropenia but can increase neutrophil counts in cats with FIV infection [Phillips et al. 2005], but can also lead to a significant increase in virus load in peripheral blood mononuclear cells during treatment by enhancing infection of lymphocytes or increased expression of FIV by infected lymphocytes [Aral et al. 2000].
Erythropoietin, EPO, is on the market as recombinant human product (rHuEPO) and is effectively used in cats with non-regenerative anaemia due to endogenous erythropoietin deficiency in chronic renal failure. FIV-infected cats treated with human erythropoietin (100 IU/kg SQ q48h) showed a gradual increase in red and white blood cell counts [Aral et al. 2000]. No increase in virus loads was observed, and thus, human erythropoietin can be used safely in FIV-infected cats.
Insulin-like growth factor-1, IGF-1, is on the market as recombinant human product (rHuIGF-1) and, besides other actions, has the ability to induce thymic growth and to stimulate T-cell function. Treatment with human insulin-like growth factor-1 resulted in a significant increase in thymus size and thymic cortical regeneration replenishing the peripheral T cell pool in experimentally FIV-infected cats [Woo et al. 1999]. It could be considered in young FIV-infected cats as supportive treatment, but there are no field studies so far to show its effect in naturally FIV-infected cats.

#Part4Therapeutic drugs

Antiviral therapy

Most antiviral drugs used in cats are licensed for humans and are specifically intended for treatment of HIV infection. Some of those can be used to treat FIV infection. However, many of the available drugs are toxic to cats or ineffective.
AZT (3’-azido-2’,3’-dideoxythymidine) is a nucleoside analogue (thymidine derivative) that blocks the reverse transcriptase of retroviruses. It has been shown that AZT inhibits FIV virus replication in vitro and in vivo; it can reduce plasma virus load, improve the immunological and clinical status of FIV-infected cats, and increases quality of life. In a placebo-controlled trial, AZT improved stomatitis in naturally infected cats [Hartmann et al. 1995]. Dosage is 5-10 mg/kg q12h PO or SQ. The higher dose should be used carefully as side effects can develop. For SQ injection, the lyophilized product should be diluted in isotonic NaCl solution to prevent local irritation. For PO application, syrup or gelatine capsules (dosage/weight individually for every cat) can be given. During treatment, a CBC should be performed regularly (weekly for the first month) because non-regenerative anaemia is a common side effect especially if the higher dosage is ABCD Guidelines on Feline Immunodeficiency Virus 13/21 used. If values are stable after the first month, a monthly check is sufficient. Cats with bone marrow suppression should not be treated. Studies in which FIV-infected cats were treated for two years showed that AZT is well tolerated. Some cats may develop a mild decrease of haematocrit initially in the first three weeks that resolves even if treatment is continued. If haematocrit drops below 20 %, discontinuation is recommended and anaemia usually resolves within a few days. Unfortunately, as in HIV, AZT-resistant mutants of FIV can arise as early as six months after initiation of treatment.
AMD3100, 1,1’-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride, JM3100, SID791, belongs to the new class of bicyclams that act as selective antagonists of the chemokine receptor CXCR4. CXCR4 is the main co-receptor for T-cell-line-adapted HIV strains, and blocking the CXCR4 receptor leads to inhibition of virus entry. FIV also uses CXCR4 for virus entry [Frey et al. 2001, Willet et al. 1997, Richardson et al. 1999, Egberink et al. 1999], and a high degree of homology exists between the human and feline CXCR4. AMD3100 is not licensed as antiviral compound but as a stem cell activator for patients that undergo bone marrow transplantation. It is effective against FIV in vitro, and in a placebo-controlled double-blind study in which 40 naturally FIV-infected cats were treated with AMD 3100 (0.5 mg/kg q12h SQ for 6 weeks), it caused a statistically significant improvement in clinical signs and decreased the proviral load in FIV-infected cats. Cats receiving AMD3100 did not show side effects [Hartmann et al. 2002].
Feline interferon-? was recently licensed for use in veterinary medicine in some European countries and Japan. Interferons are species-specific; therefore, feline interferon-? can be used life-long without stimulating antibody development. No side effects have been reported in cats. Feline interferon-? is active against FIV in vitro but so far, only one study has been performed in field cats that did not show significant changes in survival rate when compared to a placebo group [de Mari et al. 2004].
Human interferon-a has immune-modulatory effects, but also acts as a true antiviral compound by inducing a general antiviral state of cells that protects them against virus replication [Tompkins 1999]. Two common treatment regimens exist for use of human interferon-a in cats, SQ injection of high-dose (104-106 IU/kg q24h) or PO application of low-dose (1 to 50 IU/kg q24h). When given SQ in high dosage, interferon-a leads to detectable serum levels. However, it becomes ineffective after three to seven weeks due to development of neutralizing antibodies [Zeidner et al. 1990]. A placebo controlled clinical study using dose human interferon-a PO (10 IU/kg daily) prolonged CD4+ T cell survival [Pedretti et al. 2006].

Immune modulators

Immune modulators or interferon inducers are widely used medications in FIV-infected cats. It has been suggested that these agents may benefit infected animals by restoring compromised immune function, thereby allowing the patient to control viral burden and recover from the disease. There is no conclusive evidence from controlled studies that immune modulators or alternative drugs have any beneficial effects on the health or survival of asymptomatic or symptomatic FIV-infected cats. A non-specific stimulation of the immune system might even be contraindicated in FIV infection as it can lead to an increase in virus replication caused by activation of latently infected lymphocytes and macrophages, and therefore can effect a progression of disease. Hence, unspecific immune modulators with unknown effects should not be used in FIV-infected cats.