Lane H C, Zunich K M, Wilson W, Cefali F, Easter M, Kovacs J A, Masur H, Leitman S F, Klein H G, Steis R G
National Institutes of Health, Bethesda, Maryland.
Ann Intern Med. 1990 Oct 1;113(7):512-9. doi: 10.7326/0003-4819-113-7-512.
To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection.
A partially randomized outpatient trial.
Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility.
Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic).
Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly.
Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation.
Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.
研究同基因骨髓移植及外周血淋巴细胞输注联合齐多夫定在治疗人类免疫缺陷病毒（HIV）感染患者中的作用。
一项部分随机的门诊试验。
国立卫生研究院临床中心的门诊及住院设施，这是一个基于研究的转诊机构。
16例HIV感染患者（15例有症状，1例无症状）。
有症状的患者接受齐多夫定治疗，每4小时口服500毫克，共12周，同时接受6次外周血淋巴细胞输注（第10周4次，第12周2次），并使用HIV血清阴性的同卵双胞胎作为供体进行骨髓移植（在第12周）。移植后，患者被随机分配接受每4小时100毫克的齐多夫定或安慰剂治疗12个月。无症状患者在最初12周接受齐多夫定治疗，移植后停止治疗。每月进行免疫和病毒学监测。
淋巴细胞输注和骨髓移植后立即出现平均（±标准误）CD4细胞百分比增加（从19.1%±3.1%增至28.1%±3.0%），对破伤风类毒素迟发型超敏反应的患者比例增加（从13例中的4例增至13例中的11例），并且在12例接受检测的患者中有8例出现了对钥孔血蓝蛋白（一种仅供体曾接种过的主要免疫原）的迟发型超敏反应。然而，未观察到明显的临床改善，也没有整体持续的免疫改善。移植后接受齐多夫定或安慰剂治疗的患者在CD4细胞百分比、迟发型超敏皮肤试验、HIV培养或p24抗原血症方面没有差异。
尽管我们的研究结果证实了齐多夫定与细胞免疫重建联合用于治疗HIV感染患者的可行性，但结果表明这种联合治疗的任何益处至多是短暂的。未来进行细胞免疫重建的尝试可能需要采用改进的抗逆转录病毒方案以及用HIV特异性抗原对供体进行免疫接种。
