Efficacy and adverse effects of the antiviral compound plerixafor in feline immunodeficiency virus-infected cats.

IF 2.6 2区农林科学 Journal of Veterinary Internal Medicine Pub Date : 2012-05-01 Epub Date: 2012-03-30 DOI:10.1111/j.1939-1676.2012.00904.x

K Hartmann, C Stengel, D Klein, H Egberink, J Balzarini

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引用次数: 12

Abstract

Background: Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4.

Hypothesis/objectives: CXCR4 antagonist plerixafor (AMD3100, 1,1'-bis-1,4,8,11-tetraazacyclotetradekan) alone or combination with adefovir (PMEA, 9-(2-phosphonylmethoxyethyl)adenine) safe and effective for treating FIV-infected cats.

Animals: Forty naturally FIV-infected, privately owned cats.

Materials and methods: Prospective, placebo-controlled, double-blind clinical trial. Cats randomly classified into 4 treatment groups. Received AMD3100, PMEA, AMD3100 in combination with PMEA, or placebo for 6 weeks. Clinical and laboratory parameters, including CD4(+) and CD8(+) cell counts, FIV proviral and viral load measured by quantitative polymerase chain reaction (qPCR) evaluated. Additionally, FIV isolates from cats treated with AMD3100 tested for drug resistance.

Results: FIV-infected cats treated with AMD3100 caused significant decrease in proviral load compared to placebo group (2.3 ± 3.8% to 1.9 ± 3.1%, of blood lymphocytes P < .05), but did not lead to improvement of clinical or immunological variables; it caused a decrease in serum magnesium concentration without clinical signs. No development of resistance of FIV isolates to AMD3100 found during treatment period. PMEA administration improved stomatitis (stomatitis score [degree 1 - 100] PMEA group: 23 ± 19 to 11 ± 10, P < .001; AMD3100 + PMEA group: 12 ± 17 to 3 ± 5, P < .05), but did not decrease proviral or viral load and caused anemia (RBC [× 10(6) /μL] PMEA group: 9.07 ± 1.60 to 6.22 ± 2.16, P < .05; AMD3100 ± PMEA group: 8.80 ± 1.23 to 5.84 ± 1.58, P < .001).

Conclusions and clinical importance: Administration of CXCR4 antagonists, as AMD3100, can induce reduction of proviral load and may represent viable treatment of FIV-infected cats. Combination treatment with PMEA not recommended.

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抗病毒复方普立沙福对猫免疫缺陷病毒感染猫的疗效和不良反应。

背景:双环蛤衍生物通过选择性阻断趋化因子受体CXCR4抑制猫免疫缺陷病毒(FIV)的复制。假设/目的:CXCR4拮抗剂plerixafor (AMD3100, 1,1′-双-1,4,8,11-四氮杂环tetradekan)单独或与阿德福韦(PMEA, 9-(2-膦基甲氧基乙基)腺嘌呤)联合治疗fiv感染的猫安全有效。动物:40只自然感染fiv的私人养猫。材料与方法:前瞻性、安慰剂对照、双盲临床试验。猫随机分为4个治疗组。接受AMD3100、PMEA、AMD3100联合PMEA或安慰剂治疗6周。临床和实验室参数，包括CD4(+)和CD8(+)细胞计数，定量聚合酶链反应(qPCR)检测的FIV前病毒和病毒载量。此外，用AMD3100治疗猫的FIV分离株进行了耐药性测试。结果:与安慰剂组相比，AMD3100治疗fiv感染猫的前病毒载量显著降低(血液淋巴细胞2.3±3.8%至1.9±3.1%，P < 0.05)，但未导致临床或免疫变量的改善;引起血清镁浓度下降，无临床症状。在治疗期间，未发现FIV分离株对AMD3100产生耐药性。PMEA组口腔炎评分[度1 ~ 100]:23±19 ~ 11±10,P < 0.001;AMD3100 + PMEA组:12±17 ~ 3±5,P < 0.05)，但不降低原病毒或病毒载量，引起贫血(RBC [× 10(6) /μL] PMEA组:9.07±1.60 ~ 6.22±2.16,P < 0.05;AMD3100±PMEA组:8.80±1.23 ~ 5.84±1.58,P < 0.001)。结论和临床意义:给予CXCR4拮抗剂，如AMD3100，可以诱导减少原载量，可能是fiv感染猫的可行治疗方法。不建议与PMEA联合治疗。

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来源期刊

Journal of Veterinary Internal Medicine Veterinary-General Veterinary

自引率

11.50%

发文量

243

期刊介绍： The mission of the Journal of Veterinary Internal Medicine is to advance veterinary medical knowledge and improve the lives of animals by publication of authoritative scientific articles of animal diseases.