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Combination Antiretroviral Therapy and Immunophenotype of Feline Immunodeficiency Virus
Jeffrey Kim1, Elisa S Behzadi2, Mary Nehring2
1Comparative Medicine Research Unit, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
Insights
Combination antiretroviral therapy (cART) improved blood abnormalities and immune cell profiles in Feline Immunodeficiency Virus (FIV)-infected cats. This study suggests cART may be a promising treatment for FIV, offering a potential animal model for human lentiviral research.
Area of Science:
- Veterinary Medicine
- Immunology
- Virology
Background:
- Feline Immunodeficiency Virus (FIV) causes immune dysfunction in cats, mirroring human immunodeficiency virus (HIV).
- Current treatments for FIV lack definitive efficacy in improving clinical outcomes.
- Combination antiretroviral therapy (cART) is effective for HIV but not yet established for FIV.
Purpose of the Study:
- To evaluate the pharmacokinetics and clinical outcomes of cART in FIV-infected domestic cats.
- To assess the impact of cART on viral loads, proviral DNA, and lymphocyte immunophenotypes.
- To determine the stability and longevity of individual cART drugs in FIV-infected cats.
Main Methods:
- Experimentally infected FIV cats received cART (Dolutegravir, Tenofovir, Emtricitabine) or placebo for 18 weeks.
- Control groups included naïve uninfected cats.
- Viral and proviral loads were quantified using digital droplet PCR; lymphocyte subsets were analyzed by flow cytometry.
Main Results:
- cART significantly improved blood dyscrasias, normalizing them by week 16 in FIV-infected cats.
- No significant difference in viremia was observed in blood or saliva between cART and placebo groups.
- cART-treated cats showed a shift towards a Th2 immunophenotype with increased CD4+CCR4+ cells and restored Th17 cells.
Conclusions:
- cART demonstrates potential for improving clinical outcomes in FIV-infected cats.
- Dolutegravir exhibited the most favorable pharmacokinetic profile among the cART drugs tested.
- FIV-infected cats treated with cART may serve as a valuable animal model for studying lentiviral infections and immune dysregulation.
Abstract:
Feline Immunodeficiency Virus (FIV) causes progressive immune dysfunction in cats similar to human immunodeficiency virus (HIV) in humans. Although combination antiretroviral therapy (cART) is effective against HIV, there is no definitive therapy to improve clinical outcomes in cats with FIV. This study therefore evaluated pharmacokinetics and clinical outcomes of cART (2.5 mg/kg Dolutegravir; 20 mg/kg Tenofovir; 40 mg/kg Emtricitabine) in FIV-infected domestic cats. Specific pathogen free cats were experimentally infected with FIV and administered either cART or placebo treatments (n = 6 each) for 18 weeks, while n = 6 naïve uninfected cats served as controls. Blood, saliva, and fine needle aspirates from mandibular lymph nodes were collected to quantify viral and proviral loads via digital droplet PCR and to assess lymphocyte immunophenotypes by flow cytometry. cART improved blood dyscrasias in FIV-infected cats, which normalized by week 16, while placebo cats remained neutropenic, although no significant difference in viremia was observed in the blood or saliva. cART-treated cats exhibited a Th2 immunophenotype with increasing proportions of CD4+CCR4+ cells compared to placebo cats, and cART restored Th17 cells compared to placebo-treated cats. Of the cART drugs, dolutegravir was the most stable and long-lasting. These findings provide a critical insight into novel cART formulations in FIV-infected cats and highlight their role as a potential animal model to evaluate the impact of cART on lentiviral infection and immune dysregulation.
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