Samri Assia, Goodall Ruth, Burton Catherine, Imami Nesrina, Pantaleo Giuseppe, Kelleher Anthony, Poli Guido, Gotch Frances, Autran Brigitte
Laboratoire d'Immunologie Cellulaire, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
Antivir Ther. 2007;12(4):553-8.
The long-term immunological benefit of protease inhibitor (PI)-sparing antiretroviral therapy (ART) using non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains poorly investigated.
A total of 120 ART-naive, HIV-1-infected participants were included in the immunology substudy of INITIO, an international randomized trial comparing two NRTIs (didanosine + stavudine) combined with either: one NNRTI (efavirenz; EFV), one non-boosted PI (nelfinavir; NFV), or one NNRTI + one PI (EFV/NFV). CD4+ T-cell counts, HIV-1 plasma RNA load (VL), T-cell phenotype, T-cell proliferation and IFN-gamma production against opportunistic/recall and HIV-1 antigens/peptides were compared at baseline and at week (W) 96 and W156.
Participants (37 EFV, 44 NFV, 39 EFV/NFV) had similar baseline VL; median CD4+ T-cell counts/mm3 were: 144 (64-303) EFV, 212 (42-313) NFV and 257 (86-331) EFV/NFV. At W156, the proportion of patients with VL < or =50 copies/ml was not different between the arms (P=0.3). From baseline to W156 there was a significant increase in CD4+ T-cell counts (P<0.001) and in naive CD4+ T cells (P<0.001), with no difference between arms and percentages of total and activated CD8+ T cells decreased significantly (P<0.001) in all arms. The decrease in activated memory CD4+ T-cells was significantly greater in the EFV arm at W96 (P=0.03) and W156 (P=0.01), but did not persist after adjusting for baseline CD4+ T-cell counts. During follow-up, responses to opportunistic pathogens increased in all patients while specific T-cell responses to HIV-1-p24 and gp160 recombinant proteins or to Gag and Nef peptides were not restored.
Regimens using/sparing PIs provide similar levels of long-term immune reconstitution even in patients with low CD4+ T-cell counts.
使用非核苷类逆转录酶抑制剂（NNRTIs）的蛋白酶抑制剂（PI）简化抗逆转录病毒疗法（ART）的长期免疫学益处仍未得到充分研究。
共有120名未接受过ART治疗的HIV-1感染者参与了INITIO的免疫学子研究，这是一项国际随机试验，比较了两种核苷类逆转录酶抑制剂（去羟肌苷+司他夫定）与以下药物联合使用的效果：一种NNRTI（依非韦伦；EFV）、一种未增效的PI（奈非那韦；NFV）或一种NNRTI+一种PI（EFV/NFV）。在基线、第96周和第156周比较了CD4+T细胞计数、HIV-1血浆RNA载量（VL）、T细胞表型、T细胞增殖以及针对机会性/回忆性抗原和HIV-1抗原/肽的干扰素-γ产生情况。
参与者（37名使用EFV，44名使用NFV，39名使用EFV/NFV）的基线VL相似；每立方毫米CD4+T细胞计数中位数分别为：使用EFV的患者为144（64 - 303），使用NFV的患者为212（42 - 313），使用EFV/NFV的患者为257（86 - 331）。在第156周时，各治疗组中病毒载量≤50拷贝/毫升的患者比例无差异（P = 0.3）。从基线到第156周，CD4+T细胞计数（P < 0.001）和初始CD4+T细胞数量（P < 0.001）显著增加，各治疗组之间无差异，且所有治疗组中总CD8+T细胞和活化CD8+T细胞的百分比均显著下降（P < 0.001）。在第96周（P = 0.03）和第156周（P = 0.01）时，EFV组活化记忆CD4+T细胞的减少更为显著，但在对基线CD4+T细胞计数进行调整后，这种差异不再持续。在随访期间，所有患者对机会性病原体的反应均有所增加，而对HIV-1 p24和gp160重组蛋白或Gag和Nef肽的特异性T细胞反应未恢复。
即使是CD4+T细胞计数较低的患者，使用/简化PI的治疗方案也能提供相似水平的长期免疫重建。
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