Raffi Francois, Katlama Christine, Saag Michael, Wilkinson Martin, Chung Jain, Smiley Lynn, Salgo Miklos
University Hospital, Nantes, France.
Clin Infect Dis. 2006 Mar 15;42(6):870-7. doi: 10.1086/500206. Epub 2006 Feb 1.
Early virological response to antiretroviral therapy is predictive of long-term treatment outcome in therapy-naive patients. In treatment-experienced patients, such correlations are less well defined, because initial responses may be less pronounced and transient because of accumulated cross-resistance to prior therapies. Our objectives were to explore how the virological and immunological status of treatment-experienced patients at an early time point (week 12) during enfuvirtide-based therapy predicted their responses at weeks 24, 48, and 96 in the T-20 versus Optimized Regimen Only (TORO) trials.
Post hoc, modified, on-treatment and intent-to-treat analyses were performed to determine whether the relationship between virological and immunological outcomes at weeks 24, 48, and 96 were predicted by the patients' week-12 responses to therapy.
Using a modified on-treatment analysis for patients who, by week 12, achieved a decrease in their HIV-1 RNA load of > or =1 log10 copies/mL, 39.2% (95% CI, 33.6%-44.8%) and 59.5% (95% CI, 53.8%-65.1%) achieved a viral load of <50 copies/mL or <400 copies/mL at week 96, respectively, compared with 1.3% (95% CI, 0%-3.8%) and 2.6% (95% CI, 0%-6.1%) of patients, respectively, who did not achieve an early virological response. Using the same modified on-treatment analysis method for patients who, at week 12, achieved a CD4 cell count increase of > or =50 cells/mm3, 87.2% (95% CI, 82.6-91.8) maintained or improved this response through week 96, compared with 56.6% (95% CI, 47.5-65.8) of patients who did not achieve this early categorical immunological response.
Enfuvirtide-based treatment regimens are associated with a rapid and durable response. Week-12 virological and immunological responses to treatment with enfuvirtide are predictive of subsequent outcomes in triple-class treatment-experienced patients.
抗逆转录病毒疗法的早期病毒学反应可预测初治患者的长期治疗结果。在经治患者中，此类相关性的界定尚不明确，因为由于对既往疗法产生的累积交叉耐药性，初始反应可能不那么明显且较为短暂。我们的目标是在T - 20对比优化单一疗法（TORO）试验中，探讨基于恩夫韦肽治疗的经治患者在早期（第12周）的病毒学和免疫状态如何预测其在第24、48和96周的反应。
进行事后、改良、治疗中及意向性分析，以确定患者第12周的治疗反应是否能预测第24、48和96周的病毒学和免疫结果之间的关系。
采用改良治疗中分析方法，对于在第12周时HIV - 1 RNA载量下降≥1 log10拷贝/mL的患者，在第96周时分别有39.2%（95%置信区间，33.6% - 44.8%）和59.5%（95%置信区间，53.8% - 65.1%）的患者病毒载量<50拷贝/mL或<400拷贝/mL，而未实现早期病毒学反应的患者分别为1.3%（95%置信区间，0% - 3.8%）和2.6%（95%置信区间, 0% - 6.1%）。采用相同的改良治疗中分析方法，对于在第12周时CD4细胞计数增加≥50个细胞/mm³的患者，87.2%（95%置信区间，82.6 - 91.8）在第96周时维持或改善了这一反应，而未实现这一早期分类免疫反应的患者为56.6%（95%置信区间，47.5 - 65.8）。
基于恩夫韦肽的治疗方案与快速且持久的反应相关。第12周时对恩夫韦肽治疗的病毒学和免疫反应可预测三类经治患者的后续结果。
