Comparative Medicine Research Unit, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Viruses. 2023 Mar 24;15(4):822. doi: 10.3390/v15040822.
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 ( = 6 each) for 18 weeks, while = 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 CD4CCR4 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.
猫免疫缺陷病毒（FIV）在猫中引起类似于人类免疫缺陷病毒（HIV）的进行性免疫功能障碍。尽管联合抗逆转录病毒疗法（cART）对 HIV 有效，但尚无明确的治疗方法可以改善 FIV 感染猫的临床结局。因此，本研究评估了 cART（2.5 mg/kg 多替拉韦；20 mg/kg 替诺福韦；40 mg/kg 恩曲他滨）在 FIV 感染的家猫中的药代动力学和临床结局。无特定病原体的猫被实验性感染 FIV，并接受 cART 或安慰剂治疗（每组各 6 只）18 周，而 6 只未感染的未感染猫作为对照。采集血液、唾液和下颌淋巴结细针抽吸物，通过数字液滴 PCR 定量病毒和前病毒载量，并通过流式细胞术评估淋巴细胞免疫表型。cART 改善了 FIV 感染猫的血液异常，到第 16 周时恢复正常，而安慰剂猫仍存在中性粒细胞减少症，尽管在血液或唾液中未观察到病毒血症有显著差异。cART 治疗的猫表现出 Th2 免疫表型，与安慰剂猫相比，CD4CCR4 细胞的比例增加，并且与安慰剂治疗的猫相比，cART 恢复了 Th17 细胞。在 cART 药物中，多替拉韦最稳定且持久。这些发现为 FIV 感染猫新型 cART 制剂提供了重要的见解，并强调了它们作为评估 cART 对慢病毒感染和免疫失调影响的潜在动物模型的作用。
