Lange Christoph G, Lederman Michael M, Medvik Kathy, Asaad Robert, Wild Mary, Kalayjian Robert, Valdez Hernan
Center for AIDS Research, Case Western University School of Medicine, Cleveland, OH 44106, USA.
AIDS. 2003 Sep 26;17(14):2015-23. doi: 10.1097/00002030-200309260-00002.
To ascertain whether delaying the initiation of highly active antiretroviral therapy (HAART) compromises functional immune reconstitution in HIV-1 infection in persons who regain 'normal' CD4 T-cell counts after suppressive antiretroviral therapies.
Prospective open-label study carried out at two University-affiliated HIV-outpatient clinics in the USA.
Response to immunization was used as a model for in vivo functional immune competence in 29 HIV-1 infected patients with CD4 T-cell counts > 450 x 106 cells/l and HIV-RNA < 400 copies/ml for > 12 months after HAART and nine HIV-1 seronegative controls. After immunization with tetanus toxoid, diphtheria-toxoid, and keyhole limpet hemocyanin, immune response scores (IRS) were calculated using postimmunization antibody concentrations, lymphocyte proliferation, and delayed-type hypersensitivity responses to vaccine antigens.
Despite normal numbers of circulating CD4 T-cells, the CD4 T-cell nadir before HAART initiation predicted the immune response to immunization (rho = 0.5; P < 0.005) while current CD4 T-cell count did not. Likewise, CD4 T-lymphocyte expression of the co-stimulatory molecule CD28 was also an independent predictor of response to immunization (rho = 0.5; P < 0.005).
Even among persons who controlled HIV replication and normalized CD4 T-cell counts with HAART, pretreatment CD4 T-cell count and numbers of circulating CD4+CD28+ T-cells at immunization, but not current CD4 T-cell count, predict the ability to respond to vaccination. Delaying the initiation of HAART in chronic HIV-1 infection results in impaired functional immune restoration despite normalization of circulating CD4 T-cell numbers.
确定在接受抑制性抗逆转录病毒治疗后CD4 T细胞计数恢复“正常”的HIV-1感染者中，延迟启动高效抗逆转录病毒治疗（HAART）是否会损害功能性免疫重建。
在美国两家大学附属的HIV门诊诊所进行的前瞻性开放标签研究。
将免疫反应作为29例HIV-1感染患者体内功能性免疫能力的模型，这些患者在接受HAART后12个月以上，CD4 T细胞计数>450×10⁶个细胞/升且HIV-RNA<400拷贝/毫升，另有9名HIV-1血清阴性对照者。在用破伤风类毒素、白喉类毒素和钥孔戚血蓝蛋白免疫后，使用免疫后抗体浓度、淋巴细胞增殖以及对疫苗抗原的迟发型超敏反应来计算免疫反应评分（IRS）。
尽管循环CD4 T细胞数量正常，但HAART启动前的CD4 T细胞最低点可预测免疫反应（rho=0.5；P<0.005），而当前的CD4 T细胞计数则不能。同样，共刺激分子CD28的CD4 T淋巴细胞表达也是免疫反应的独立预测指标（rho=0.5；P<0.005）。
即使在通过HAART控制HIV复制且CD4 T细胞计数恢复正常的人群中，免疫前的CD4 T细胞计数和循环CD4⁺CD28⁺ T细胞数量可预测疫苗接种反应能力，而当前的CD4 T细胞计数则不能。在慢性HIV-1感染中延迟启动HAART，尽管循环CD4 T细胞数量恢复正常，但功能性免疫恢复仍会受损。
