Clinic of Small Animal Medicine, LMU University of Munich, Munich, Germany.
J Vet Intern Med. 2012 May-Jun;26(3):483-90. doi: 10.1111/j.1939-1676.2012.00904.x. Epub 2012 Mar 30.
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.
Forty naturally FIV-infected, privately owned cats.
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.
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).
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.
双环胺衍生物通过选择性阻断趋化因子受体 CXCR4 来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-1,4,8,11-四氮杂环十四烷）单独或与阿德福韦（PMEA，9-(2-膦酰甲氧基乙基)腺嘌呤）联合使用，治疗感染 FIV 的猫是安全有效的。
40 只自然感染 FIV 的私人拥有的猫。
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。评估临床和实验室参数，包括 CD4(+)和 CD8(+)细胞计数、通过定量聚合酶链反应 (qPCR) 测量的 FIV 前病毒和病毒载量。此外，还测试了接受 AMD3100 治疗的猫的 FIV 分离物是否具有耐药性。
与安慰剂组相比，接受 AMD3100 治疗的 FIV 感染猫的前病毒载量显着下降（血液淋巴细胞的 2.3 ± 3.8% 至 1.9 ± 3.1%，P <.05），但并未导致临床或免疫变量的改善；它导致血清镁浓度降低，没有临床症状。在治疗期间未发现 FIV 分离株对 AMD3100 的耐药性发展。PMEA 给药改善了口炎（口炎评分[1-100 度]PMEA 组：23 ± 19 至 11 ± 10，P <.001；AMD3100 + PMEA 组：12 ± 17 至 3 ± 5，P <.05），但未降低前病毒或病毒载量，并导致贫血（RBC[×10(6)/μL]PMEA 组：9.07 ± 1.60 至 6.22 ± 2.16，P <.05；AMD3100 ± PMEA 组：8.80 ± 1.23 至 5.84 ± 1.58，P <.001）。
CXCR4 拮抗剂（如 AMD3100）的给药可诱导前病毒载量降低，可能代表了治疗感染 FIV 的猫的可行方法。不建议联合使用 PMEA 进行治疗。
