Swindells Susan, Jiang Hongyu, Mukherjee A Lisa, Winters Mark, Bosch Ronald J, Katzenstein David
University of Nebraska Medical Center, Omaha, NE, USA.
HIV Clin Trials. 2011 Mar-Apr;12(2):79-88. doi: 10.1310/hct1202-79.
We hypothesized that drug resistance mutations would impact clinical outcomes associated with HIV-1 infection.
A matched case-control study of participants in AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT). Cases experienced an AIDS-defining event (ADE) or mortality, and controls did not. One hundred thirty-four cases were identified and matched to a total of 266 controls by age, sex, treatment regimen, and length of follow-up. Both cases and controls had HIV RNA levels of ≥ 500 copies/mL within 24 weeks of an event. Population-based genotyping at or near the time of the event was used to evaluate the impact of resistance mutations on incidence of ADE and/or death using conditional logistic regression models.
One hundred four cases and 183 controls were analyzed. Median time to event was 99 weeks; 6 cases were deaths. At baseline, cases had lower CD4 (median 117 vs 235 cells/mm3; P < .0001) and higher HIV RNA levels (median 205,000 vs 57,000 copies/mL; P = .003). No significant differences in resistance were seen between cases and controls.
In this rigorously designed case-control study, lower CD4 cell counts and higher virus loads, not antiretroviral drug resistance, were strongly associated with ADE and mortality.
我们假设耐药性突变会影响与HIV-1感染相关的临床结局。
对艾滋病临床试验组纵向关联随机试验（ALLRT）的参与者进行配对病例对照研究。病例经历了艾滋病定义事件（ADE）或死亡，而对照未经历。共识别出134例病例，并根据年龄、性别、治疗方案和随访时间与266例对照进行配对。病例和对照在事件发生后24周内的HIV RNA水平均≥500拷贝/毫升。在事件发生时或接近事件发生时进行基于人群的基因分型，使用条件逻辑回归模型评估耐药性突变对ADE和/或死亡发生率的影响。
分析了104例病例和183例对照。事件发生的中位时间为99周；6例为死亡病例。基线时，病例的CD4细胞计数较低（中位数分别为117和235个细胞/mm3；P < .0001），HIV RNA水平较高（中位数分别为205,000和57,000拷贝/毫升；P = .003）。病例和对照之间在耐药性方面未见显著差异。
在这项设计严谨的病例对照研究中，较低的CD4细胞计数和较高的病毒载量，而非抗逆转录病毒药物耐药性，与ADE和死亡率密切相关。
