Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston Salem, North Carolina 27104, USA.
AIDS. 2011 Jan 28;25(3):367-77. doi: 10.1097/QAD.0b013e328341dcc0.
There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown.
This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett's (QTcB) and Fredericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group.
Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P < 0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P < 0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P < 0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P < 0.01).
Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences.
关于蛋白酶抑制剂对 QT 和 PR 间期持续时间的心电图测量值的影响，存在相互矛盾的报告。中断使用蛋白酶抑制剂对 QT 和 PR 进展的影响也尚不清楚。
本分析纳入了 SMART 研究中的 3719 名参与者，其中 1879 名随机分配接受间歇性抗逆转录病毒治疗（ART）（药物保留组），其余接受这些药物连续治疗（病毒抑制组）。线性回归分析比较了四种利托那韦增强的蛋白酶抑制剂（蛋白酶抑制剂/r）方案[沙奎那韦（SQV/r）、洛匹那韦（LPV/r）、阿扎那韦（ATV/r）和其他蛋白酶抑制剂/r]与非增强蛋白酶抑制剂与非核苷类逆转录酶抑制剂（NNRTI）方案的巴泽特（QTcB）和弗雷德里西亚（QTcF）心率校正 QT 和 PR。比较了药物保留组和病毒抑制组在随机分组后 12 个月和 24 个月时 QTcB、QTcF 和 PR 的变化。
进入研究时，平均 QTcB、QTcF 和 PR 持续时间分别为 415、406 和 158ms。研究开始时，49%的参与者正在服用基于 NNRTI（无蛋白酶抑制剂）的方案，31%的参与者服用了增强的蛋白酶抑制剂，最常见的是 LPV/r。在调整基线因素后，增强的蛋白酶抑制剂组的 QTcB 和 QTcF 水平没有差异（分别为 P=0.26 和 P=0.34）。对于接受任何增强的蛋白酶抑制剂治疗的患者，与 NNRTI 组相比，QTcB 低 1.5ms（P=0.04）。含有增强或非增强的蛋白酶抑制剂的方案与 NNRTI 组相比，PR 间隔均显著延长（P<0.01）。调整后，增强的蛋白酶抑制剂与 NNRTI 组之间的差异为 5.11ms（P<0.01）；对于非增强的蛋白酶抑制剂，差异为 3.00ms（P<0.01）。ART 中断后，增强和非增强的蛋白酶抑制剂组的 PR 持续时间均下降，与病毒抑制组相比，增强的蛋白酶抑制剂 ART 中断 24 个月后 PR 间隔的变化有统计学意义（P<0.01）。
与 NNRTI 为基础的方案相比，不同的蛋白酶抑制剂方案对 QT 的影响相似，程度最小。所有基于蛋白酶抑制剂的方案（增强或非增强）均与 PR 延长有关，中断蛋白酶抑制剂方案可减少 PR 延长。需要进一步研究以证实本研究的结果，并评估差异的临床意义。
