Sherding: FIV 12/7/04

Feline Immunodeficiency Virus Infection

Bob Sherding, DVM, DACVIM
Ohio State University; Columbus, Ohio, USA
Description and Pathogenesis
Feline immunodeficiency virus (FIV) is in the retrovirus family, subfamily Lentivirinae. FIV
was originally isolated from a cattery in California in 1986, but retrospective assays of stored
sera have shown that FIV has been widespread in the worlds cat population since at least the
1960s. FIV has a tropism for lymphocytes, macrophages, salivary glands, and the CNS. FIV
primarily infects and gradually destroys selected populations of T-lymphocytes. This cytopathic
effect causes a progressive loss of CD4 helper T-lymphocytes in the early stages and a loss of
CD8 T-lymphocytes as well in the later stages. There is also decreased cytokine production and
impaired response to cytokines. After a prolonged asymptomatic latent period that can extend for
years, the progressive loss of T-lymphocytes results in an immunodeficiency syndrome
characterized by chronic and recurrent infections. Infection is lifelong and eventually fatal.
Various FIV subtypes have been identified based on differences in the envelope gene. Subtypes
vary in geographic distribution and influence cell tropism and pathogenicity.
Epidemiology
FIV has been found worldwide and throughout North America. In a nationwide survey of
27,976 high-risk cats presenting to U.S. veterinarians, 7.4% overall were infected with FIV,
compared with 13.3% infected with feline leukemia virus and 1.5% co-infected with both
(IDEXX; 1991). Of symptomatic cats, 11.6% were infected. Of asymptomatic cats, 4.0% were
infected. Of low-risk cats living indoors in single-cat households, 1.4% were infected.
High-risk/high-incidence situations include free-roaming outdoor pet or stray (feral) cats,
cats exposed to outdoor cats, and cats living in large multi-cat households that frequently
introduce new cats. The seroprevalence in countries such as Japan and Italy with many freeroaming cats can be as high as 25 to 30%. Low-risk/low incidence situations include indoor pet
cats in single-cat households and cats in closed, well-controlled catteries. The incidence in
purebred cats is low.
Male cats outnumber females 3 to 1 (see Transmission section). FIV affects cats of all ages,
but the incidence increases with age. Because of an extended asymptomatic latent period that is
typical for lentiviruses, most FIV-infected cats that have clinical signs are older than 6 years.
Transmission
FIV is shed in saliva and transmitted primarily through direct bite wound inoculation during
territorial fights (hence the higher incidence in free-roaming males). Transmission can also occur
through transfusion of contaminated blood. Transmission through intimate contact during
cohabitation is unlikely but not impossible. Contact transmission has been suspected on rare
occasions in catteries, but the route or mechanism of transmission is undetermined. Fomite
transmission is very unlikely. Experimentally, acute and chronically infected queens may
transmit FIV to kittens in utero (congenital infection) and through infected milk (lactogenic

Sherding: FIV 12/7/04

infection). These are considered to be of minor importance under natural conditions. FIV has
also been transmitted transmucosally by oral, vaginal, and rectal inoculation of virus and through
artificial insemination of infected semen; however, these routes may not be important in nature.
Clinical Signs
Acute Primary Phase of Infection
This stage begins at 4 to 6 weeks post-exposure and the effects are transient and usually go
unnoticed. Manifestations can include transient fever, neutropenia, lymphopenia, and enlarged
lymph nodes characterized by follicular hyperplasia and plasma cell infiltration. Rare
complications during this stage can include sepsis, cellulitis, pustular facial dermatitis, anemia,
diarrhea, and stomatitis.
Asymptomatic Phase of Infection
This stage is a prolonged latency period of variable duration that may persist for years before
signs of immunodeficiency occur. Persistent lymphadenomegaly may develop during this stage.
Chronic Terminal Phase of Infection
Advanced FIV infection is characterized by an acquired immunodeficiency syndrome that
predisposes to chronic recurrent opportunistic infections with waxing and waning signs that
progressively worsen over months or years. Chronic or recurrent bacterial infections may involve
the oral cavity (stomatitis, gingivitis, periodontitis); respiratory system (rhinitis, pneumonia,
pyothorax); intestines (enterocolitis, nonspecific diarrhea); skin (pustular dermatitis, abscesses,
purulent otitis); and urinary tract (cystitis, pyelonephritis). A wide variety of opportunistic
infectious diseases also can occur in FIV-infected cats.
Other manifestations can include any of the following: recurrent fevers, progressive weight
loss, generalized lymphadenomegaly, hyperglobulinemia (polyclonal hypergammaglobulinemia),
anemia, lymphopenia, and neutropenia (in advanced cases; also increased susceptibility to
griseofulvin-induced neutropenia). Immune-mediated diseases and lymphocytic polymyositis
have been associated with FIV. Infected cats have increased risk for neoplasia; such as
lymphoma, myeloproliferative disease, and carcinoma (squamous cell, mammary, etc).
FIV also can cause encephalopathy, especially in kittens, characterized by compulsive
pacing, circling, agitation, rage, twitching of face/tongue, lip-sucking, dementia, disrupted sleep
patterns, hiding, loss of litter training, seizures, and abnormal frontal cortex electrodiagnostics
(EEG, BAEP, and VEP).
Ocular findings reported in FIV-infected cats include anterior uveitis, glaucoma, pars
planitis, retinal hemorrhages, and retinal degeneration.

Sherding: FIV 12/7/04

Nephropathy has been associated with FIV infection, although the relationship is poorly
understood. Findings may include azotemia, proteinuria, and renal lesions of
glomerularschlerosis, microcystic tubular dilatation, and interstitial nephritis and fibrosis.
Diagnosis
Routine Lab Findings
Abnormalities on routine lab evaluations are inconsistent, but can include
hyperglobulinemia (20%); mild nondegenerative anemia (18-36%); lymphopenia (30-50%);
neutrophilia (22-35%); neutropenia (11-34%); and thrombocytopenia (8-16%).
Assays for FIV Antibody
The diagnosis of FIV is usually based on the demonstration of anti-FIV serum antibodies
using assays such as ELISA, IFA, or Western blot. Because FIV antibodies indicate prior
exposure and infection, and because FIV infection is lifelong, a confirmed positive FIV antibody
test result indicates that the virus is present in the cat and will remain so for life (except when
colostral antibody affects the test in cats < 6 months of age). Vaccination for FIV eliminates the
usefulness of these antibody titer tests because of vaccine-induced antibodies.
Seroconversion usually occurs 2 to 4 weeks post-infection, but it occasionally takes up to 16
weeks. Titers sometimes decline terminally. Passively-acquired maternal FIV antibodies
acquired from colostrum can cause positive results in uninfected kittens for up to 6 months of
age; thus, reevaluate all positive kittens at 6 months of age to determine their true status.
The accuracy of popular in-office ELISA screening tests for FIV is high, but false positive
results may occur in up to 5% of cats (or up to 20% if weak positives are overinterpreted as
definitive positives); thus, in low-risk, asymptomatic cats repeat confirm ELISA positives with
an IFA test or ideally by Western blot at a commercial lab. The Western blot detects antibodies
against specific viral proteins and is considered the gold standard for confirming ELISApositive results. False negative results can occur in the early stages of acute infection before
seroconversion has occurred or rarely in the terminal stages of immunodeficiency when antibody
levels may be depressed.
Assays to Detect Virus
Polymerase chain reaction (PCR) assay, antigen ELISA, and virus isolation can be used to
detect FIV, but these are not yet routinely available for clinical use. These are useful for early
detection of infection prior to seroconversion and for diagnosis of terminal infections when
antigen levels may be high and antibody levels are depressed. Research labs can isolate FIV from
blood, tissues, and body fluids of infected cats.
Treatment
No currently available treatment is effective for eliminating FIV once infection is
established; thus, it should be assumed that infection is lifelong and incurable. However,
asymptomatic cats can live for years before developing clinical signs, and symptomatic cats

Sherding: FIV 12/7/04

often can be managed for many months with antibiotics to control secondary infections
combined with supportive care. Cats ill with FIV-related bacterial infections can sometimes
respond dramatically to antibiotics. Treat each infection episode as it arises, using culture and
sensitivity guidance. Use fluid therapy and nutritional support as indicated by the patient's needs.
Treat stomatitis with metronidazole (10 mg/kg PO q12h) and clindamycin (12.5 mg/kg PO
q12h). In some cats stomatitis improves with prednisone (5 mg per cat PO q12h) or
immunotherapy. Refractory stomatitis may require full-mouth dental extractions.
Do not use griseofulvin (dermatophyte drug) in FIV-positive cats because of increased risk of
drug-induced neutropenia.
Prevent exposure to other infectious diseases because of lowered resistance. Continue routine
vaccinations in cats at risk of exposure, but killed products are preferred. Until the late stages of
infection, FIV-positive cats retain the ability to respond to vaccination.
Anti-Viral Therapy
Specific antiviral therapy is routinely used to treat humans infected with HIV. Some of these
anti-HIV drugs are too toxic in cats, or very expensive and difficult to obtain for veterinary use.
Treatment of FIV-infected cats with the reverse transcriptase inhibitor, zidovudine (AZT or
ZDV; 15 mg/kg, PO or SC, q12h), a nucleoside analogue, has improved immunologic status and
produced regression of stomatitis. Zidovudine (Retrovir) is moderately expensive and can cause
Heinz body anemia or bone marrow toxicity; thus, treated cats should have their hemogram
monitored.
Immune Modulator Therapy
Immune modulator therapy using low-dose oral interferon (30 units/day on alternate weeks)
may improve attitude & appetite. The effects of immune modulators on survival are
inconclusive.
In the terminal stages of FIV the prognosis for response to treatment is poor, as indicated by
persistent anemia or leukopenia, severe weight loss, or CNS signs.
Prevention
Keep infected cats isolated from uninfected cats until more is known about cat-to-cat contact
transmission (although non-bite transmission is considered very rare). Prevent exposure by
advising owners to not allow cats to roam free and recommend neutering of male cats (to reduce
roaming and fighting). Breeding of FIV-infected cats is not recommended.
An FIV vaccine is now available (Fort Dodge); however, evidence of clinically relevant
protection is not yet established for this vaccine. A major disadvantage of vaccination is that the
resulting antibodies react on standard FIV diagnostic tests; thereby eliminating the usefulness of
standard diagnostic tests. The vaccine guidelines of the American Association of Feline
Practitioners does not currently recommend routine use of FIV vaccination in cats.
Public Health Risks:
FIV is a feline-specific virus and there is no evidence that it causes human infection.
However, FIV-infected cats may harbor various other pathogens because of their
immunodeficiency that can infect humans who are immunosuppressed.

Sherding: FIV 12/7/04

Diagnostic Testing Guidelines for FeLV

(Bob Sherding, DVM, DACVIM)
AAFP Guidelines for FeLV Testing

FeLV status of all cats should be known.

Kittens can be tested at any age (in utero and lactogenic transmission occurs).
Test cats presented for FeLV vaccination.
-Avoids existing FeLV carriers from being misidentified as vaccination failures.
Test new cats before entering a household of healthy cats.
Test cats with potential recent exposure.
Test cats with signs of illness consistent with FeLV.

ELISA Test versus IFA Test

ELISA Test
The ELISA test is the preferred screening test (most sensitive; widely available for rapid
in-office screening.
The ELISA test detects FeLV viral antigen in blood, plasma, serum, tears, saliva, milk, or
any other body fluid. Clear serum and plasma are most accurate.
The ELISA test using tears or saliva has a higher rate of false positives than blood, and is
not appropriate for routine testing, except for mass screening of populations of cats.
IFA Test
The IFA test is the preferred confirmatory test, and correlates best with persistent
infection.
The IFA test detects cell-associated FeLV viral antigen within circulating WBCs and
platelets. It indicates bone marrow replication of FeLV; thus, an advanced stage.
AAFP Guidelines for FeLV Test Interpretation

Key Point-- Transiently FeLV-positive cats may recover and stay healthy, whereas
persistently viremic cats (defined as positive for >3 months) usually die of FeLV-related
disease.
Weak ELISA tests are equivocal and should be repeated. Most are not true positives.
Positive tear or saliva ELISA tests should be confirmed using serum or plasma.
Use a validated IFA test, or a 3-month repeat of the ELISA test to confirm any healthy
ELISA-positive cat before it is considered persistently viremic.
Cats that test negative on initial ELISA screening may take up to 3 months from exposure
to become positive; thus, only re-testing after 3 months can truly confirm FeLV-free
status.