Lancet. 2013 Jun 15;381(9883):2091-9. doi: 10.1016/S0140-6736(13)61164-2.
Uncertainty exists about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NtRTI). We compared a second-line regimen combining two new classes of drug with a WHO-recommended regimen.
We did this 96-week, phase 3b/4, randomised, open-label non-inferiority trial at 37 sites worldwide. Adults with HIV-1 who had confirmed virological failure (plasma viral load >500 copies per mL) after 24 weeks or more of first-line treatment were randomly assigned (1:1) to receive ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). The randomisation sequence was computer generated with block randomisation (block size four). Neither participants nor investigators were masked to allocation. The primary endpoint was the proportion of participants with plasma viral load less than 200 copies per mL at 48 weeks in the modified intention-to-treat population, with a non-inferiority margin of 12%. This study is registered with ClinicalTrials.gov, number NCT00931463.
We enrolled 558 patients, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1·8%, 95% CI -4·7 to 8·3), fulfilling the criterion for non-inferiority. 993 adverse events occurred in 271 participants in the control group versus 895 in 270 participants in the raltegravir group, the most common being gastrointestinal.
The raltegravir regimen was no less efficacious than the standard of care and was safe and well tolerated. This simple NtRTI-free treatment strategy might extend the successful public health approach to management of HIV by providing simple, easy to administer, effective, safe, and tolerable second-line combination antiretroviral therapy.
University of New South Wales, Merck, AbbVie, the Foundation for AIDS Research.
对于使用非核苷类逆转录酶抑制剂（NNRTI）加两种核苷或核苷酸逆转录酶抑制剂（NtRTI）的一线联合抗逆转录病毒治疗发生病毒学失败的 HIV-1 感染者，最佳治疗方法尚不确定。我们比较了联合使用两类新药的二线方案与世界卫生组织推荐的方案。
这是一项在全球 37 个地点进行的 96 周、3b/4 期、随机、开放标签的非劣效性试验。在一线治疗 24 周或更长时间后，经确认发生病毒学失败（血浆病毒载量>500 拷贝/ml）的 HIV-1 成人患者，按 1:1 比例随机分配（随机分组）接受利托那韦增强洛匹那韦加两种或三种 NtRTI（对照组）或利托那韦增强洛匹那韦加雷特格韦（雷特格韦组）。随机序列由计算机生成，采用区块随机化（区块大小为 4）。参与者和研究者均未对分组进行盲法。主要终点为改良意向治疗人群中 48 周时病毒载量<200 拷贝/ml 的患者比例，非劣效性边界为 12%。该研究在 ClinicalTrials.gov 注册，编号为 NCT00931463。
我们共纳入 558 例患者，其中 541 例（对照组 271 例，雷特格韦组 270 例）纳入主要分析。48 周时，对照组 219 例（81%）患者和雷特格韦组 223 例（83%）患者达到主要终点（差异 1.8%，95%CI-4.7 至 8.3），符合非劣效性标准。对照组 271 例患者中发生 993 例不良事件，雷特格韦组 270 例患者中发生 895 例，最常见的是胃肠道事件。
雷特格韦方案的疗效不劣于标准治疗，且安全且耐受良好。这种简单的不含 NtRTI 的治疗策略可能通过提供简单、易于管理、有效、安全和耐受的二线联合抗逆转录病毒治疗，扩展成功的公共卫生管理 HIV 的方法。
新南威尔士大学、默克、艾伯维、艾滋病研究基金会。
