Cozzi-Lepri Alessandro, Phillips Andrew N, Clotet Bonaventura, Mocroft Amanda, Ruiz Lidia, Kirk Ole, Lazzarin Adriano, Wiercinska-Drapalo Alicja, Karlsson Anders, Lundgren Jens D
Research Department of Infection & Population Health, Royal Free and University College Medical School, London, UK.
AIDS. 2008 Oct 18;22(16):2187-98. doi: 10.1097/QAD.0b013e328310e04f.
OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death.
Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window.
Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed.
We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005).
Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.
研究开始抗逆转录病毒治疗2年后检测到的HIV耐药性与随后进展为艾滋病和死亡风险之间的关系。
病毒学失败定义为在开始抗逆转录病毒治疗（基线）后0.5至2年的时间窗口内连续两次病毒载量超过400拷贝/毫升。根据病毒学失败的证据以及在该时间窗口内是否检测到对一种、两种或三种药物类别具有国际艾滋病协会耐药突变，对患者进行分组。
采用Kaplan-Meier曲线进行标准生存分析，并使用基线时定义的时间固定协变量的Cox比例风险回归模型。
我们在欧洲艾滋病临床数据库（EuroSIDA）中研究了8229例开始抗逆转录病毒治疗且至少有2年临床随访的患者。在38814人年的随访期间，我们观察到829例艾滋病事件和571例死亡，新的艾滋病和死亡的总体发病率为每100人年随访3.6例[95%置信区间（CI）：3.4 - 3.8]。从基线开始96个月时，无病毒学失败证据的患者中新诊断为艾滋病或死亡的比例为20.3%（95% CI：17.7 - 22.9），而有病毒学失败且对三种药物类别有突变的患者中这一比例为53%（39.3 - 66.7）（P = 0.0001）。多变量分析证实风险几乎相差两倍（调整后的相对风险 = 1.8，95% CI：1.2 - 2.7，P = 0.005）。
尽管本研究显示治疗失败时检测到的耐药性与临床进展风险之间存在关联，但仍需要进一步研究以阐明耐药性是反映依从性差还是通过药物选择耗尽直接增加临床事件的风险。
