Gandhi Tejal, Nagappan Vijayalakshmi, Cinti Sandro, Wei Wei, Kazanjian Powel
University of Michigan Health System, Ann Arbor, MI 48109-5378, USA.
Clin Infect Dis. 2007 Oct 15;45(8):1085-92. doi: 10.1086/521937. Epub 2007 Sep 14.
Some treatment-experienced patients with highly drug-resistant human immunodeficiency virus (HIV) infection have no option but to continue to receive an incompletely suppressive regimen (ISR). We performed a study to determine their long-term immunologic and virologic responses to ISR, to investigate risks for immunologic or virologic failure, and to examine for the occurrence of new drug-resistance mutations.
Antiretroviral treatment-experienced HIV-infected patients with a genotype sensitivity score < or = 1, an HIV load > 1000 copies/mL, and no available optimized regimen were included in the study. The proportion of patients treated with ISR who developed immunologic failure (defined as a 25% reduction in the CD4 cell count from the baseline level) and virologic failure (defined as a > or = 0.5-log10 increase in the HIV load from the baseline level) was determined. Cox proportional hazards analysis was used to investigate variables associated with immunologic or virologic failure. New drug-resistant mutations were calculated in 27 patients with sequential genotypes available.
Forty-seven patients (median duration of prior antiretroviral therapy, 89 months; median CD4 cell count, 277 cells/mm3; and median HIV load, 19,728 copies/mL) had multiple HIV mutations (a median of 5 nucleoside reverse-transcriptase inhibitor mutations, 1 nonnucleoside reverse-transcriptase inhibitor mutation, and 6 protease inhibitor mutations; median genotype sensitivity score, 0) at baseline. By 48 months after ISR use, 43% had developed immunologic failure, and 22% had developed virologic failure. None of the studied variables (i.e., age, < 50 years; baseline HIV load, > 100,000 copies/mL; baseline CD4 cell count, < 200 cells/mm3; or inclusion of lamivudine in the treatment regimen) were associated with immunologic or virologic failure. New nucleoside reverse-transcriptase inhibitor mutations occurred in 63% of patients, and new primary protease inhibitor mutations occurred in 52.6% of protease inhibitor recipients. No deaths occurred. A total of 8.5% of patients experienced a new AIDS-defining event.
Most patients with highly drug-resistant HIV infection who were treated with an ISR maintain durable immunologic and virologic responses. New drug-resistant mutations occur frequently.
一些有治疗经历的高度耐药人类免疫缺陷病毒（HIV）感染患者别无选择，只能继续接受不完全抑制性治疗方案（ISR）。我们开展了一项研究，以确定他们对ISR的长期免疫和病毒学反应，调查免疫或病毒学失败的风险，并检测新的耐药突变的发生情况。
研究纳入了有抗逆转录病毒治疗经历、基因型敏感性评分≤1、HIV载量>1000拷贝/mL且无可用优化治疗方案的HIV感染患者。确定接受ISR治疗的患者发生免疫失败（定义为CD4细胞计数较基线水平降低25%）和病毒学失败（定义为HIV载量较基线水平增加≥0.5 log10）的比例。采用Cox比例风险分析来研究与免疫或病毒学失败相关的变量。对27例有连续基因型数据的患者计算新的耐药突变。
47例患者（既往抗逆转录病毒治疗的中位持续时间为89个月；CD4细胞计数中位数为277个/mm3；HIV载量中位数为19,728拷贝/mL）在基线时存在多个HIV突变（核苷类逆转录酶抑制剂突变中位数为5个、非核苷类逆转录酶抑制剂突变1个、蛋白酶抑制剂突变6个；基因型敏感性评分中位数为0）。在使用ISR后48个月时，43%的患者发生了免疫失败，22%的患者发生了病毒学失败。所研究的变量（即年龄<50岁、基线HIV载量>100,000拷贝/mL、基线CD4细胞计数<200个/mm3或治疗方案中包含拉米夫定）均与免疫或病毒学失败无关。63%的患者出现了新的核苷类逆转录酶抑制剂突变，52.6%接受蛋白酶抑制剂治疗的患者出现了新的蛋白酶抑制剂原发性突变。无死亡病例发生。共有8.5%的患者发生了新的艾滋病定义事件。
大多数接受ISR治疗的高度耐药HIV感染患者维持了持久的免疫和病毒学反应。新的耐药突变频繁发生。
