Patarca Roberto, Isava Alejandro, Campo Rafael, Rodriguez Nelson J, Nunez Enriqueta, Alter Michael, Marchette Margaret, Sanabia Mirtha M, Mitchell Charles, Rivera Delia, Scott Gwendolyn, Jayaweera Dushyantha, Moreno Jose, Boulanger Catherine, Kolber Michael, Mask Cindy W, Sierra Eduardo Meneses, Vallejo Ricardo, Page J Brian, Klimas Nancy G, Fletcher Mary Ann
E.M. Papper Laboratory of Clinical Immunology and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33101, USA.
J Environ Pathol Toxicol Oncol. 2003;22(3):201-34. doi: 10.1615/jenvpathtoxoncol.v22.i3.40.
Throughout most of the past century, physicians could offer patients no treatments for infections caused by viruses. The experience with treatment of infection by human immunodeficiency virus (HIV) has changed the way healthcare workers deal with viral infections and has triggered a growing rate of discovery and use of antiviral agents, the first fruits of the expanding genomics revolution. HIV treatment also provides an informative paradigm for pharmacogenomics because control of infection and its consequences is limited by the development of viral drug resistance and by host factors. This report summarizes studies published to date on the significance of testing of HIV-1 resistance to antiretroviral drugs. The only Food and Drug Administration-approved kit for HIV drug resistance testing by genotypic sequencing is commercially available through Visible Genetics, Inc. Genotyping sequencing alone is most likely an adequate test to assist in the therapeutic decision-making process for previous regimen failure, for treatment-naïve patients in areas of high prevalence of transmitted resistant virus, and for pregnant women. However, in exceptional cases of highly complex mutation patterns and extensive cross-resistance, it may be useful to obtain a phenotype test, because that result may more easily identify drugs to which virus is least resistant. There are no published clinical trials results on the usefulness of the so-called virtual phenotype over genotypic sequencing alone. Not only has the paradigm of viral pharmacogenomics in the form of HIV genotypic sequencing been useful in treating other viral diseases, but it is also important to the real-life implementation of the growing discipline ofgenomics or molecular medicine. The application of this paradigm to the thousands of potential therapeutic targets that have become available through the various human genome projects will certainly gradually change the landscape of diagnosis and management of many diseases, including cancer.
在过去一个世纪的大部分时间里，医生无法为病毒引起的感染患者提供治疗方法。人类免疫缺陷病毒（HIV）感染的治疗经验改变了医护人员应对病毒感染的方式，并引发了抗病毒药物发现和使用的增长速度，这是不断扩展的基因组学革命的首批成果。HIV治疗也为药物基因组学提供了一个信息丰富的范例，因为感染及其后果的控制受到病毒耐药性发展和宿主因素的限制。本报告总结了迄今为止发表的关于检测HIV-1对抗逆转录病毒药物耐药性的意义的研究。唯一获得美国食品药品监督管理局批准的用于通过基因测序进行HIV耐药性检测的试剂盒可通过Visible Genetics公司商业获取。仅基因分型测序很可能是一种足够的检测方法，可协助处理既往治疗方案失败的情况、在传播耐药病毒高流行地区的初治患者以及孕妇的治疗决策过程。然而，在高度复杂的突变模式和广泛交叉耐药的特殊情况下，进行表型检测可能有用，因为该结果可能更容易识别病毒耐药性最低的药物。目前尚无关于所谓虚拟表型单独优于基因测序的有用性的已发表临床试验结果。不仅HIV基因测序形式的病毒药物基因组学范例在治疗其他病毒疾病方面有用，而且对于基因组学或分子医学这一不断发展的学科在现实生活中的应用也很重要。将这一范例应用于通过各种人类基因组计划可得的数千个潜在治疗靶点，肯定会逐渐改变包括癌症在内的许多疾病的诊断和管理格局。
