Chomont Nicolas, Trautmann Lydie, Routy Jean-Pierre, Sékaly Rafick-Pierre
Laboratoire d'Immunologie, Centre de Recherche CHUM Saint-Luc, Montreal, Quebec, Canada.
Curr Opin HIV AIDS. 2007 Mar;2(2):116-22. doi: 10.1097/COH.0b013e3280287a4d.
The escape of HIV-1 is a cardinal feature of the virus and a major hindrance to the development of effective therapeutic strategies. In highly active antiretroviral therapy-treated patients, the virus is subjected to selective pressures from cellular immune response directed against the viral proteome and antiretroviral treatment targetting a few genes of the HIV-1 genome. This review will focus on the relationship between these two pressures and its potential advantage in the development of novel immune therapies.
Recent studies have investigated the conflicting selective forces between viral fitness and escape to immunological and therapeutic pressures in natural HIV infection and the SIV model. Simultaneous pressures driven by cytotoxic T lymphocytes and highly active antiretroviral therapy could potentially reduce viral fitness, leading to better control of the viral load. Two studies have described a potential therapeutic vaccine strategy against viral escape mutant epitopes from reverse transcriptase inhibitors.
The emergence of multidrug-resistant viruses is associated with enhanced T-cell-mediated immune response as a possible consequence of reduced viral fitness. Amino acid substitutions generate potential cytotoxic T-lymphocyte epitopes that may elicit new reactivities against mutated viruses. Both could significantly enhance the immune response through direct and indirect mechanisms.
HIV-1逃逸是该病毒的一个主要特征，也是有效治疗策略研发的主要障碍。在接受高效抗逆转录病毒治疗的患者中，病毒会受到针对病毒蛋白质组的细胞免疫反应以及针对HIV-1基因组少数基因的抗逆转录病毒治疗所产生的选择性压力。本综述将聚焦于这两种压力之间的关系及其在新型免疫疗法研发中的潜在优势。
近期研究调查了自然HIV感染和SIV模型中病毒适应性与逃避免疫和治疗压力之间相互冲突的选择力。细胞毒性T淋巴细胞和高效抗逆转录病毒治疗共同产生的压力可能会降低病毒适应性，从而更好地控制病毒载量。两项研究描述了一种针对来自逆转录酶抑制剂的病毒逃逸突变表位的潜在治疗性疫苗策略。
多药耐药病毒的出现与T细胞介导的免疫反应增强有关，这可能是病毒适应性降低的结果。氨基酸替换产生潜在的细胞毒性T淋巴细胞表位，可能引发针对突变病毒的新反应。两者都可通过直接和间接机制显著增强免疫反应。
