Plana Montserrat, Garcia Felipe, Oxenius Annette, Ortiz Gabriel M, Lopez Anna, Cruceta Anna, Mestre Gabriel, Fumero Emilio, Fagard Catherine, Sambeat Maria Antonia, Segura Ferran, Miró José M, Arnedo Mireia, Lopalcos Lucia, Pumarola Tomas, Hirschel Bernard, Phillips Rodney E, Nixon Douglas F, Gallart Teresa, Gatell Jose M
Clinic Institute of Infectious Diseases and Immunology, IDIBAPS, Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain.
J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):791-9. doi: 10.1097/00126334-200407010-00005.
To analyze the dynamics of both HIV-1-specific CD4 and CD8 T-cell responses during structured treatment interruptions (STIs) in chronically HIV-1-infected (CHI) patients and to correlate them with the viral set point achieved.
Forty-five early-stage CHI patients who were on highly active antiretroviral therapy (HAART) for at least 1 year and underwent STI were included. Plasma viral load (VL), peripheral blood mononuclear cell (PBMC) lymphoproliferative (LPR) response to HIV p24 protein, and HIV-1 epitope-specific interferon-gammarelease from CD8 T cells were measured over a minimum study period of 2 years.
VL set point during final STI was both significantly lower than, and positively correlated to, baseline VL (P < 0.0001: mean VL reduction 0.77 log10, and r = 0.42, P = 0.004, respectively). CD4 LPRs to p24 increased significantly (P = 0.001) between day 0 of the first STI cycle and 4th STI but decreased thereafter. VL set point during final STI was significantly and negatively correlated with LPRs to p24 at both 2nd STI and 4th STI. Nevertheless, at week 52, 12 weeks after the end of the last STI, LPRs were weak and transient in all patients and were not correlated with VL set point. Moreover, the magnitude and breadth of HIV-1-specific CD8 T-cell responses increased significantly (P < 0.0001) between day 0 and week 52. The largest increases occurred during the final STI. Even though VL reached set point by week 12 of the final STI, HIV-1-specific CD8 T-cell responses did not stabilize but rather increased until the end of the follow-up and did not correlate with plasma VL (r = 0.01, P = 0.88).
STIs do not lead to control of viral replication in CHI patients, probably due to the fact that boosted CTL responses lack strong and durable helper T-cell responses. To reset the VL set point, new approaches that effectively augment and preserve helper T-cell responses should be investigated.
分析慢性HIV-1感染（CHI）患者在结构化治疗中断（STI）期间HIV-1特异性CD4和CD8 T细胞反应的动态变化，并将其与达到的病毒载量设定值相关联。
纳入45例接受高效抗逆转录病毒治疗（HAART）至少1年并经历STI的早期CHI患者。在至少2年的研究期内测量血浆病毒载量（VL）、外周血单个核细胞（PBMC）对HIV p24蛋白的淋巴细胞增殖反应（LPR）以及CD8 T细胞释放的HIV-1表位特异性干扰素-γ。
最终STI期间的VL设定值显著低于基线VL，且与基线VL呈正相关（P<0.0001：平均VL降低0.77 log10，r = 0.42，P = 0.004）。在第一个STI周期的第0天和第4个STI之间，对p24的CD4 LPR显著增加（P = 0.001），但此后下降。最终STI期间的VL设定值与第2个STI和第4个STI时对p24的LPR显著负相关。然而，在最后一次STI结束12周后的第52周，所有患者的LPR均微弱且短暂，与VL设定值无关。此外，在第0天至第52周之间，HIV-1特异性CD8 T细胞反应的幅度和广度显著增加（P<0.0001）。最大的增加发生在最终STI期间。尽管在最终STI的第12周时VL达到设定值，但HIV-1特异性CD8 T细胞反应并未稳定，而是持续增加直至随访结束，且与血浆VL无关（r = 0.01，P = 0.88）。
STI不会导致CHI患者的病毒复制得到控制，可能是因为增强的CTL反应缺乏强大而持久的辅助性T细胞反应。为了重置VL设定值，应研究有效增强和保留辅助性T细胞反应的新方法。
