Kaufmann Gilbert R, Khanna Nina, Weber Rainer, Perrin Luc, Furrer Hansjakob, Cavassini Matthias, Ledergerber Bruno, Vernazza Pietro, Bernasconi Enos, Rickenbach Martin, Hirschel Bernard, Battegay Manuel
Division of Infectious Diseases, University Hospital, Basel, Switzerland.
Antivir Ther. 2004 Apr;9(2):263-74.
Information about the virological response to sequential highly active antiretroviral therapy (HAART) for HIV infection is limited. The virological response to four consecutive therapies was evaluated in the Swiss HIV Cohort.
Retrospective analysis in an observational cohort.
1140 individuals receiving uninterrupted HAART for 4.8 +/- 0.6 years were included. The virological response was classified as success (<400 copies/ml), low-level (LF: 400-5000 copies/ml) or high-level failure (HF: >5000 copies/ml). Potential determinants of the virological response, including patient demographics, treatment history and virological response to previous HAART regimens were analysed using survival and logistic regression analyses.
40.1% failed virologically on the first (22.0% LF; 18.1% HF), 35.1% on the second (14.2% LF; 20.9% HF), 34.2% on the third (9.9% LF; 24.3% HF) and 32.7% on the fourth HAART regimen (9% LF; 23.7% HF). Nucleoside pre-treatment (OR: 2.34; 95% CI: 1.67-3.29) and low baseline CD4 T-cell count (OR: 0.79/100 cells rise; 95% CI: 0.72-0.88) increased the risk of HF on the first HAART. Virological failure on HAART with HIV-1 RNA levels exceeding 1000 copies/ml predicted a poor virological response to subsequent HAART regimens. A switch from a protease inhibitor- to a non-nucleoside reverse transcriptase inhibitor-containing regimen significantly reduced the risk of HF. Multiple switches of HAART did not affect the recovery of CD4 T lymphocytes.
Multiple sequential HAART regimens do not per se reduce the likelihood of long-term virological suppression and immunological recovery. However, early virological failure increases significantly the risk of subsequent unfavourable virological responses. The choice of a potent initial antiretroviral drug regimen is therefore critical.
关于人类免疫缺陷病毒（HIV）感染序贯高效抗逆转录病毒治疗（HAART）的病毒学应答信息有限。在瑞士HIV队列中评估了对连续四种治疗方案的病毒学应答情况。
对一个观察性队列进行回顾性分析。
纳入1140名接受了4.8±0.6年不间断HAART治疗的个体。病毒学应答被分类为成功（<400拷贝/毫升）、低水平（LF：400 - 5000拷贝/毫升）或高水平失败（HF：>5000拷贝/毫升）。使用生存分析和逻辑回归分析来分析病毒学应答的潜在决定因素，包括患者人口统计学特征、治疗史以及对先前HAART方案的病毒学应答情况。
在第一个HAART方案中，40.1%出现病毒学失败（22.0%为LF；18.1%为HF），第二个方案中为35.1%（14.2%为LF；20.9%为HF），第三个方案中为34.2%（9.9%为LF；24.3%为HF），第四个HAART方案中为32.7%（9%为LF；23.7%为HF）。核苷类药物预处理（比值比：2.34；95%置信区间：1.67 - 3.29）和基线CD4 T细胞计数低（比值比：每升高100个细胞为0.79；95%置信区间：0.72 - 0.88）增加了第一个HAART方案出现HF 的风险。HIV - 1 RNA水平超过1000拷贝/毫升的HAART方案出现病毒学失败预示着对后续HAART方案的病毒学应答较差。从含蛋白酶抑制剂的方案转换为含非核苷类逆转录酶抑制剂的方案可显著降低HF风险。多次更换HAART方案并未影响CD4 T淋巴细胞的恢复。
多个序贯HAART方案本身并不会降低长期病毒学抑制和免疫恢复的可能性。然而，早期病毒学失败会显著增加后续出现不良病毒学应答的风险。因此，选择有效的初始抗逆转录病毒药物方案至关重要。
