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: Maki Arai, Donald D Earl, Janet K Yamamoto
• Journal: Veterinary immunology and immunopathology (Vet Immunol Immunopathol) Vol. 85 Issue 3-4 Pg. 189-204 (Mar 2002) ISSN: 0165-2427 [Print] Netherlands
• PMID: 11943320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

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)