K Hartmann, C Stengel, D Klein, H Egberink, J Balzarini
{"title":"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。","authors":"K Hartmann, C Stengel, D Klein, H Egberink, J Balzarini","doi":"10.1111/j.1939-1676.2012.00904.x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4.</p><p><strong>Hypothesis/objectives: </strong>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.</p><p><strong>Animals: </strong>Forty naturally FIV-infected, privately owned cats.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions and clinical importance: </strong>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.</p>","PeriodicalId":17462,"journal":{"name":"Journal of Veterinary Internal Medicine","volume":"26 3","pages":"483-90"},"PeriodicalIF":2.6000,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1939-1676.2012.00904.x","citationCount":"12","resultStr":"{\"title\":\"Efficacy and adverse effects of the antiviral compound plerixafor in feline immunodeficiency virus-infected cats.\",\"authors\":\"K Hartmann, C Stengel, D Klein, H Egberink, J Balzarini\",\"doi\":\"10.1111/j.1939-1676.2012.00904.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4.</p><p><strong>Hypothesis/objectives: </strong>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.</p><p><strong>Animals: </strong>Forty naturally FIV-infected, privately owned cats.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions and clinical importance: </strong>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.</p>\",\"PeriodicalId\":17462,\"journal\":{\"name\":\"Journal of Veterinary Internal Medicine\",\"volume\":\"26 3\",\"pages\":\"483-90\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2012-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1111/j.1939-1676.2012.00904.x\",\"citationCount\":\"12\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Veterinary Internal Medicine\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1111/j.1939-1676.2012.00904.x\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2012/3/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Veterinary Internal Medicine","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1111/j.1939-1676.2012.00904.x","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2012/3/30 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Efficacy and adverse effects of the antiviral compound plerixafor in feline immunodeficiency virus-infected cats.
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.
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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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.
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