Kilby J Michael, Lee Ha Youn, Hazelwood J Darren, Bansal Anju, Bucy R Patterson, Saag Michael S, Shaw George M, Acosta Edward P, Johnson Victoria A, Perelson Alan S, Goepfert Paul A
Division of Infectious Diseases and 1917 HIV Research Clinic, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294-2050, USA.
AIDS. 2008 May 11;22(8):957-62. doi: 10.1097/QAD.0b013e3282fbd1da.
Compare the initial phases of virologic decay when acute/early and advanced HIV-infected adults are administered the same treatment regimen.
Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression.
We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIV-specific immune responses at baseline, and the presence of drug resistance-conferring mutations.
There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence.
Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum.
比较给予急性/早期和晚期HIV感染成人相同治疗方案时病毒学衰减的初始阶段。
对一项先前完成的前瞻性治疗试点研究进行数学建模,该研究涉及未接受过治疗的早期和晚期免疫抑制患者。
我们分析了一项治疗方案的数据,该方案中18例急性或近期HIV-1血清转化患者和6例晚期艾滋病患者接受了相同的四联抗逆转录病毒治疗方案。通过对频繁的病毒载量测量数据拟合数学模型来比较初始治疗反应,以计算病毒清除的第一阶段和第二阶段动力学,同时也比较24周内的病毒载量抑制情况。还对患者在蛋白酶抑制剂药物水平、基线时的HIV特异性免疫反应以及耐药性突变的存在情况进行了全面比较。
无论是否将蛋白酶抑制剂水平纳入模型或假设抗病毒药物有效性为100%,两组中相当高水平病毒血症的第一阶段清除率均无统计学意义上的显著差异。相比之下,急性/早期患者的持续反应比晚期患者差,这反映出依从性不稳定。
尽管经过多年的免疫破坏干预,但在HIV疾病谱的两端,治疗初期的病毒学衰减似乎是相同的。