Bristol Veterinary School, University of Bristol & The Linnaeus Group, Bristol & Shirley, UK
Management wise, retrovirus-FeLV-infected cats should be kept indoors, neutered and not fed raw meat or allowed to hunt (risk of toxoplasmosis), and preventative ecto- and endo-parasite treatment should be given.7,8 Ideally they should be kept in single-cat households. If the latter is not possible, the retrovirus status of in-contacts should be considered in optimising care. As FIV is primarily transmitted by fighting and biting, cats in stable multi-cat households may not transmit infection between them although the risk is always there. Cats in contact with FeLV FeLV-infected cats that do not show any evidence of FeLV infection (regressive as well as progressive infection) should be vaccinated, although protection cannot be guaranteed.
Close monitoring of retrovirus-FeLV-infected cats is encouraged via scheduling of veterinary/nursing appointments every 6 months for a full clinical examination and subsequent investigations as required. Weight loss, lymphadenopathy, clinical signs of upper respiratory infection (e.g., ocular or nasal discharge) and oral health are particularly important to note, as well as ophthalmic examination. Routine haematology, serum biochemistry, urinalysis, urine culture and faecal examination may be indicated and should be done routinely at least once a year.
Vaccination is reserved for cats that are likely to contact other cats and should ideally comprise inactivated vaccines;9 the potential benefits and risks of vaccinating FIV (and FeLV)-FeLV-infected cats should be weighed up in individual cats.7 The vaccination of FeLV-positive cats against FeLV is of no benefit.8
Supportive care is obviously important. Cats in the terminal phase (acquired immunodeficiency syndrome AIDs) of FIV infection may require fluid therapy, nutritional support, dental care and treatment of opportunistic infections (i.e., dentistry, mouth washes, antibiotics, etc.). Opportunistic infections need to be treated appropriately but prolonged treatment may be required for retrovirus-FeLV-infected cats. FeLV-associated lymphoma can undergo chemotherapy/radiotherapy; studies variably report that FeLV is a negative prognostic indicator for cats with lymphoma so chemotherapy can still be given.10 Blood transfusions may be indicated for anaemic cases but the ethics of collecting blood from a donor cat needs to be carefully considered.
Retrovirus-FeLV-infected cats with immune-mediated diseases (e.g., immune-mediated haemolytic anaemia, immune-mediated polyarthritis) can benefit from the cautious use of prednisolone (2 mg/kg/day; lower end of immunosuppressive dose range in cats).
Human interferon-α (hIFN-α) and recombinant feline interferon-ω (rIFN-ω; Virbagen Omega; Virbac) are both type I IFNs that have immunomodulating effects due to interaction with specific cell receptors and induction of gene expression for cytokines involved in innate immunity. Type I IFNs are produced by virally FeLV-infected cells. rIFN-ω is preferentially used in cats as neutralising antibodies can be induced by hIFN-α. The beneficial action of IFN in retroviral FeLV-infected cats is believed to be due to modulation of innate immunity as clinical improvements occur without changes in levels of viral DNA/RNA or immunological (e.g., CD4/CD8 ratio) parameters,11 and decreased pro-inflammatory stimuli12 and increased acute phase proteins13 are seen.
Two IFN-ω treatment regimens have been described; high dose SQ injections (1 million units/kg SQ SID for 5 consecutive days for 3 courses starting on days 0, 14 and 60; the licensed protocol for Virbagen Omega) or low doses PO (0.1 million units/cat PO SID for 90 days). A placebo-controlled double-blind study using the SQ IFN-ω treatment regime in FeLV or dual FeLV-FIV naturally FeLV-infected cats14 showed a significant improvement in clinical scores at 4 months (not reassessed thereafter) and survival at 9 months (non-significant at 12 months) in treated c.f. untreated cats. All cats also received supportive care (but not glucocorticoids). No significant changes in haematological parameters were seen. Another study with SQ IFN-ω11 in FeLV or FIV naturally FeLV-infected cats found a significant improvement in clinical score in treated (~9 months after starting treatment) c.f. untreated cats, especially those that were sick, as well as improved haematological variables, although significance was not reported for these. The length of the positive effect seen in this study suggested that the effect of IFN- ω persisted beyond the treatment period. Another study15 reported SQ IFN-ω treatment in FeLV, FIV or dual FeLV/FIV naturally FeLV-infected cats in a shelter environment; significant improvements in clinical scores were seen in the cats following treatment (c.f. before treatment as the cats acted as their own controls), but when cats were more closely evaluated according to infecting agent, only those FeLV-infected with FIV alone (and especially those showing more marked clinical signs of gingivitis/gingivostomatitis) showed a significant improvement. A recent study16 used oral IFN-ω treatment in naturally FIV-FeLV-infected cats and compared this to previous SQ IFN-ω treatment results15 (i.e., this was the control group used, and no placebo control group was used in the study); it found no significant difference in results and thus suggested that oral IFN-ω treatment could be considered over SQ IFN-ω, as it is cheaper and easier to administer. However the SQ route was said to induce a marked clinical improvement in a larger proportion of cats, and so, may be preferable when cats with more severe signs are treated.16,
Zidovudine (AZT) (5 mg/kg PO or SQ BID; some use 10 mg/kg PO or SQ BID, and this higher dose should be used carefully, as side effects can develop—see below). For SQ injection, the lyophilised product should be diluted in isotonic saline solution to prevent local irritation. For PO application, syrup or gelatin capsules can be given. AZT is a nucleoside reverse transcriptase inhibitor; it can reduce plasma viral loads, increase CD4/CD8 ratios and improve clinical status, particularly in FIV-FeLV-infected cats with stomatitis or neurological disease; results have not been as favourable in FeLV-FeLV-infected cats, although some mild benefits have been reported. However, non-regenerative anaemia and neutropenia can result, and cats with bone marrow suppression should not be given AZT. Haematology should be monitored weekly in the 1st month and monthly thereafter if counts are stable; treatment is stopped if PCV<20%. AZT-resistant mutant FIV viruses can arise during long-term (years) treatment.17 Fozivudine, an alternative agent without haematological side effects that showed promise for acute experimental FIV infection,18 did not show benefits in chronically FIV-FeLV-infected cats.19
Plerixafor, a selective antagonist of the CXCR4 receptor, which FIV binds to, given SQ BID resulted in significantly decreased FIV proviral load without side effects in a placebo-controlled double-blind study of naturally FIV-FeLV-infected cats, but no improvement in clinical or immunological variables (CD4/CD8) or RNA loads was seen.20
Raltegravir, an oral integrase inhibitor, has recently been evaluated in the treatment of experimental FeLV-FeLV-infected cats;21 9 weeks of treatment, started 15 weeks post-infection, was associated with significantly reduced plasma FeLV RNA loads (although to a lower level than seen with this agent in other host species such as humans), but FeLV RNA load levels rebounded 4 weeks following termination of treatment, and prevention of viraemia did not occur.
Recombinant human erythropoietin (rHuEPO) may be effective in retrovirus-FeLV-infected cats with non-regenerative anaemias, which is surprising as endogenous EPO levels are likely to be high. Experimental FIV-FeLV-infected cats treated with rHuEPO showed a gradual increase in erythrocyte and white blood cell counts without increases in viral loads,22 whereas the same study found that cats treated with recombinant human granulocyte macrophage colony stimulating factor (rHuGM-CSF) showed increased viral loads (and formation of anti-GMCSF antibodies).
No studies have been done in FeLV-FeLV-infected cats. However, rHuEPO (e.g., Epoetin) have been associated with anti-EPO antibody formation in cats (~30%), worsening the severity of anaemia, but recent successful reports of a longer-acting rHuEPO, called darbepoetin, in renal cases23 has not yet been associated with the formation of anti-EPO antibodies, so this may be promising for retroviral FeLV-infected cats, too.
Antioxidants to combat oxidative stress have been suggested as treatment for FIV-FeLV-infected cats, as oxidative stress has been implicated in the progression of HIV infection in humans. The antioxidant superoxide dismutase was found to be associated with an improvement in the CD4+ to CD8+ ratio in FIV-FeLV-infected oral supplemented cats over the short 30-day period studied,24 but further studies are required.
References are available upon request.