| Abstract | In vitro and in vivo prophylactic and therapeutic efficacy of AZT/3TC treatment was evaluated against feline immunodeficiency virus (FIV) infection. In vitro studies utilized FIV-infected peripheral blood mononuclear cells (PBMCs) or FIV-infected T-cell lines treated with AZT (azidothymidine) alone, 3TC alone, or AZT/3TC combination and tested for anti-FIV activity and drug toxicity. AZT/3TC combination had additive to synergistic anti-FIV activities in primary PBMC but not in chronically infected cell lines. In vivo studies consisted of four treatment groups (n=15) of SPF cats receiving AZT/3TC combination (5-75 mg/kg/drug PO BID for 8 or 11 weeks) and one control group (n=9) receiving oral placebo. Group I (n=6, 150 mg/kg/drug/day) was treated starting 3 days pre-FIV inoculation, whereas Group II (n=3, 150 mg/kg/drug/day) and Group III (n=3, 100 mg/kg/drug/day) treatments were simultaneous with FIV inoculation. Group IV treatment (n=3, 100 mg/kg/drug/day) was initiated 2 weeks post-FIV inoculation. All cats were monitored for drug toxicity and FIV infection. Eighty-three percent of cats in Group I and 33% of cats in Groups II and III were completely protected from FIV infection. A significant delay in infection and antibody seroconversion was observed in all unprotected cats from Groups I, II and III. Group IV cats had only a slight delay in FIV antibody seroconversion. Adverse drug reactions (anemia and neutropenia) were observed at high doses (100-150 mg/kg/drug/day) were reversible upon lowering the dose (20 mg/kg/drug/day). In contrast, AZT/3TC treatment had no anti-FIV activity in chronically infected cats. Furthermore, severe clinical symptoms caused by adverse drug reactions were observed in some of these cats. Overall, AZT/3TC treatment is effective for prophylaxis but not for therapeutic use in chronically FIV-infected cats. |
| Authors | Maki Arai, Donald D Earl, Janet K Yamamoto
(Affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA.)
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| Journal | Veterinary immunology and immunopathology
(Vet Immunol Immunopathol)
Vol. 85
Issue 3-4
Pg. 189-204
(Mar 2002)
ISSN: 0165-2427 Netherlands |
| PMID | 11943320
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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| Chemical References |
- Anti-HIV Agents
- Antibodies, Viral
- Lamivudine
- Zidovudine
|
| Topics |
- Animals
- Anti-HIV Agents
(adverse effects, immunology, therapeutic use)
- Antibodies, Viral
(blood)
- CD4-Positive T-Lymphocytes
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cat Diseases
(drug therapy, immunology, virology)
- Cats
- Drug Synergism
- Drug Therapy, Combination
- Feline Acquired Immunodeficiency Syndrome
(drug therapy, immunology, virology)
- Flow Cytometry
- Immunodeficiency Virus, Feline
(genetics, immunology, metabolism)
- Lamivudine
(adverse effects, immunology, therapeutic use)
- Random Allocation
- Viral Load
(veterinary)
- Zidovudine
(adverse effects, therapeutic use)
|
