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Thus, a comprehensive analysis of cART’s impact on viral and proviral loads, salivary shedding, and clinical morbidity from acute to chronic infection may further aid in the design of cART. Other antiretroviral drugs are also neuroprotective and decrease the viral load in chronically infected cats. Previous studies investigating the treatment of FIV have demonstrated that antiretroviral drugs can effectively suppress FIV infection in culture. As cART with tenofovir disoproxil fumarate, emtricitabine, and dolutegravir has demonstrated lentiviral suppression in humans and nonhuman primates, we thus developed a novel cART protocol and evaluated its efficacy as a treatment for cats infected with FIV. The synergy of multiple antiretroviral classes-often referred to as combination antiretroviral therapy (cART) or highly active antiretroviral therapy (HAART)-has demonstrated improved patient outcomes and is the gold-standard for antiretroviral therapy. The recent introduction of dolutegravir, a next-generation integrase inhibitor, is a preferred adjunctive treatment in HIV patients, causing a strong viral suppression of HIV with improved patient tolerance. Antiretroviral drugs used against HIV have also been shown to exhibit anti-FIV effects in vitro, including reverse transcription inhibitors such as tenofovir disoproxil fumarate and emtricitabine. 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.Ĭombination antiretroviral therapy has been comprehensively studied as a treatment for primate immunodeficiency viruses (HIV, SIV), but there is a paucity of works in the literature investigating it as a treatment for FIV. Of the cART drugs, dolutegravir was the most stable and long-lasting. 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. 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. 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.

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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. 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. Although combination antiretroviral therapy (cART) is effective against HIV, there is no definitive therapy to improve clinical outcomes in cats with FIV. Feline Immunodeficiency Virus (FIV) causes progressive immune dysfunction in cats similar to human immunodeficiency virus (HIV) in humans.