Carr A, Emery S, Kelleher A, Law M, Cooper D A
HIV Medicine Unit, St. Vincent's Hospital, Sydney, Australia.
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Dec 1;13(4):320-6. doi: 10.1097/00042560-199612010-00004.
CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy. We compared CD8+ lymphocyte responses in seven trials of nucleoside or non-nucleoside analog reverse transcriptase inhibitors and in two trials of ritonavir, a HIV protease inhibitor. Nucleoside analog and non-nucleoside analog reverse transcriptase inhibitor monotherapy resulted in no substantial changes in CD8+ counts relative to baseline or placebo. Combination nucleoside analog therapy resulted in variable peak responses (-145 to +240 cells/mm3), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8+ cells/mm3, which remained significantly above baseline for 32 weeks. There was a significant correlation (Rs 0.61, p = 0.01) between the peak CD4+ cell and CD8+ responses to each therapy, but no significant correlation between the peak viral load responses and peak CD8+ cell responses. These findings suggest that the greater CD8+ response seen with ritonavir may be due to its specific inhibition of HIV protease and also that the CD8+ response is dependent on new CD4+ cell production. The CD8+ lymphocyte proliferation observed with protease inhibitor therapy could result in improved suppression of HIV replication by the immune system and should be confirmed in a prospective trial comparing protease inhibitors with both nucleoside and non-nucleoside analog therapies.
CD8 + T淋巴细胞可能通过人类白细胞抗原（HLA）限制的细胞毒性作用以及可溶性HIV抑制因子的产生，介导宿主对人类免疫缺陷病毒（HIV）感染的重要反应。CD8 +淋巴细胞对于抑制许多导致HIV感染患者发生机会性疾病的潜伏病原体也很重要。目前尚未对CD8 +淋巴细胞计数对抗逆转录病毒疗法的反应进行系统分析。我们比较了核苷或非核苷类似物逆转录酶抑制剂的七项试验以及HIV蛋白酶抑制剂利托那韦的两项试验中CD8 +淋巴细胞的反应。核苷类似物和非核苷类似物逆转录酶抑制剂单一疗法相对于基线或安慰剂而言，并未使CD8 +计数发生实质性变化。联合核苷类似物疗法导致峰值反应各异（-145至+240个细胞/mm³），在0至12周内仍显著高于基线水平。相比之下，利托那韦单一疗法使CD8 +细胞峰值增加892个/mm³，在32周内仍显著高于基线水平。每种疗法的CD4 +细胞峰值与CD8 +反应之间存在显著相关性（Rs 0.61，p = 0.01），但病毒载量峰值反应与CD8 +细胞峰值反应之间无显著相关性。这些发现表明，利托那韦观察到的更大的CD8 +反应可能归因于其对HIV蛋白酶的特异性抑制作用，并且CD8 +反应依赖于新的CD4 +细胞产生。蛋白酶抑制剂疗法观察到的CD8 +淋巴细胞增殖可能会导致免疫系统对HIV复制的抑制作用增强，这一点应在前瞻性试验中进行确认，该试验将蛋白酶抑制剂与核苷和非核苷类似物疗法进行比较。
