Connolly K J, Allan J D, Fitch H, Jackson-Pope L, McLaren C, Canetta R, Groopman J E
Section of Infectious Disease, New England Deaconess Hospital, Boston, Massachusetts.
Am J Med. 1991 Nov;91(5):471-8. doi: 10.1016/0002-9343(91)90182-w.
To evaluate the safety and hematologic tolerance of 2'-3'-dideoxyinosine (didanosine, ddI) in subjects with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and prior hematologic intolerance to zidovudine.
A Phase I trial with two dose groups at a single-center, university-affiliated hospital ambulatory care center. Of 30 subjects enrolled, 21 had AIDS and nine had AIDS-related complex. All had CD4 lymphocyte counts less than 0.2 x 10(9)/L at entry. Didanosine was administered orally twice daily at a total daily dose of 750 mg or 1,500 mg for 12 weeks. Subjects who completed the 12-week study continued to receive ddI at the lower dose. All subjects were monitored for toxicity. Virologic and immunologic response markers were also measured.
For the group as a whole, there was no significant decrease in mean hemoglobin level or leukocyte or platelet counts. The dose-limiting toxicity was peripheral neuropathy. Other significant toxicities included pancreatitis and hypocalcemia. Uric acid elevations were common but were without clinical consequence. A sustained decrease in serum p24 antigen of at least 50% was noted in 42% of subjects who were p24 antigen-positive at entry. The mean CD4 lymphocyte count showed an initial increase that was not sustained over the 12-week study. All subjects remained anergic to skin testing.
Didanosine is well tolerated hematologically in some patients with prior significant hematologic intolerance to zidovudine. The toxicity profile for ddI differs from that of zidovudine and includes peripheral neuropathy and pancreatitis. Changes in CD4 lymphocyte number and HIV p24 antigen levels in some patients suggest antiviral activity of ddI in this population.
评估2′-3′-双脱氧肌苷（去羟肌苷，ddI）在获得性免疫缺陷综合征（AIDS）或AIDS相关综合征且先前对齐多夫定存在血液学不耐受的受试者中的安全性和血液学耐受性。
在一所大学附属医院门诊护理中心进行的单中心I期试验，设两个剂量组。30名入组受试者中，21例患有AIDS，9例患有AIDS相关综合征。所有受试者入组时CD4淋巴细胞计数均低于0.2×10⁹/L。去羟肌苷每日口服两次，总日剂量为750mg或1500mg，共服用12周。完成12周研究的受试者继续接受较低剂量的ddI治疗。对所有受试者进行毒性监测。还测量了病毒学和免疫学反应标志物。
对于整个组而言，平均血红蛋白水平、白细胞或血小板计数均无显著下降。剂量限制性毒性为周围神经病变。其他显著毒性包括胰腺炎和低钙血症。尿酸升高很常见，但无临床后果。在入组时p24抗原呈阳性的受试者中，42%的受试者血清p24抗原持续下降至少50%。平均CD4淋巴细胞计数在12周研究期间最初有所增加，但未持续。所有受试者皮肤试验仍无反应。
在一些先前对齐多夫定有明显血液学不耐受的患者中，去羟肌苷在血液学方面耐受性良好。ddI的毒性特征与齐多夫定不同，包括周围神经病变和胰腺炎。一些患者CD4淋巴细胞数量和HIV p24抗原水平的变化表明ddI在该人群中具有抗病毒活性。
