title: Is AZT/3TC therapy effective against FIV infection or immunopathogenesis?
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.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA.
authors.forename: Maki
authors.initials: M
authors.lastname: Arai
authors.forename: Donald D
authors.initials: DD
authors.lastname: Earl
authors.forename: Janet K
authors.initials: JK
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002371:Cat Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D002415:Cats; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019259:Lamivudine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D011897:Random Allocation; D019562:Viral Load / Q000662:veterinary; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D019259:Lamivudine; D015215:Zidovudine