Li T S, Tubiana R, Katlama C, Calvez V, Ait Mohand H, Autran B
Laboratoire d'Immunologie Cellulaire, Hôpital Pitié-Salpêtière, Paris, France.
Lancet. 1998 Jun 6;351(9117):1682-6. doi: 10.1016/s0140-6736(97)10291-4.
Highly active antiretroviral therapy (HAART) decreases viral load and increases CD4 T-cell counts in patients with advanced HIV-1 infection. Whether HAART can improve CD4 T-cell function, and the biological characteristics affecting immune reconstitution, remain unclear. We undertook an open prospective pilot study to address these issues. Both treatment-naïve and previously treated patients were included.
20 patients (seven naïve, 13 previously treated) were treated with one protease inhibitor and two reverse-transcriptase inhibitors and followed up for 12 months. We measured CD4-cell proliferation in response to cytomegalovirus and tuberculin antigens and counted subsets of CD4 cells at baseline and months 1, 3, 6, 9, and 12. Patients who had no antigen-specific reactivity at baseline but developed it while receiving HAART were classified as immunological responders.
Four patients had antigen-specific reactivity at baseline compared with 14 at month 12 (p <0.001). Between month 3 and month 12 viral load fell by a median of 1.5 log copies/mL from baseline (4.6 log copies/mL) and CD4-cell count increased by a median of 63/microL (from 93/microL). Ten patients (six of seven naïve, four of 13 previously treated) were immunological responders. They differed significantly from the ten non-responders in that their viral-load reduction was sustained for 12 months, the increase in CD4 count was greater, and they showed an early increase in memory CD4 T cells with an increase of naïve T cells.
HAART can induce sustained recovery of CD4 T-cell reactivity against opportunistic pathogens in severely immunosuppressed patients. This recovery depends not on baseline values but on the amplitude and duration of viral-load reduction and the increase of memory CD4 T cells.
高效抗逆转录病毒疗法（HAART）可降低晚期HIV-1感染患者的病毒载量并增加CD4 T细胞计数。HAART是否能改善CD4 T细胞功能以及影响免疫重建的生物学特性仍不清楚。我们开展了一项开放性前瞻性试点研究以解决这些问题。未接受过治疗和先前接受过治疗的患者均被纳入研究。
20例患者（7例未接受过治疗，13例先前接受过治疗）接受一种蛋白酶抑制剂和两种逆转录酶抑制剂治疗，并随访12个月。我们检测了巨细胞病毒和结核菌素抗原刺激下的CD4细胞增殖情况，并在基线以及第1、3、6、9和12个月时对CD4细胞亚群进行计数。基线时无抗原特异性反应但在接受HAART治疗期间出现反应的患者被归类为免疫反应者。
与12个月时的14例相比，基线时有4例患者具有抗原特异性反应（p<0.001）。在第3个月至第12个月期间，病毒载量较基线水平（4.6 log拷贝/mL）中位数下降了1.5 log拷贝/mL，CD4细胞计数中位数增加了63/μL（从93/μL）。10例患者（7例未接受过治疗者中的6例，13例先前接受过治疗者中的4例）为免疫反应者。他们与10例无反应者有显著差异，在于其病毒载量下降持续了12个月，CD4计数增加更多，并且记忆性CD4 T细胞早期增加，同时幼稚T细胞也增加。
HAART可诱导严重免疫抑制患者针对机会性病原体的CD4 T细胞反应持续恢复。这种恢复不取决于基线值，而是取决于病毒载量下降的幅度和持续时间以及记忆性CD4 T细胞的增加。
