Background Lamivudine+dolutegravir maintenance dual therapy (DT) could be less effective than three-drug therapies (TT) in the context of resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (NRTIs). The “ARCA” database was queried to test this hypothesis with a trial-emulation strategy. Methods People living with HIV on 2NRTI plus either a protease inhibitor or a non-NRTI, switching to DT or dolutegravir-based TT, were followed-up from the first HIV-RNA<50 cps/mL (baseline) to virological failure (VF, i.e., 2 consecutive HIV-RNA≥50 cps/ml or one HIV-RNA≥200 cp/mL). Those switching to DT within 6 months were assigned to the “treatment”-arm, all other patients to the “control”-arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. By using inverse-probability of censoring weight (IPCW)-Cox regression models, we calculated hazard-ratios of VF for DT versus TT, stratified for the presence of RAMs. Results Overall, 626 people (204 on DT, 422 on TT; 73% men, mean age 44 years) were analyzed. Ten and 31 VF occurred with DT and TT, respectively, over a median of 5.8 years. Compared with a fully-active TT, the DT had similar efficacy (aHR: 0.88, 95% CI 0.29-2.61; p=0.812) when full susceptibility was confirmed at historical genotype. When in both groups previous M184V/I was present, the risk of VF was higher for DT but not statistically significant (versus TT, aHR 3.06, 95% CI 0.45-20.84; p=0.252). Conclusions DT was not associated with a statistically significant higher risk of VF than dolutegravir-based TT.

中文翻译：

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拉米夫定加多替拉韦与以多替拉韦为基础的三药治疗方案对病毒学抑制的艾滋病毒感染者的疗效

背景 在核苷逆转录酶抑制剂 (NRTI) 耐药相关突变 (RAM) 的情况下，拉米夫定 + 多替拉韦维持双重疗法 (DT) 可能不如三药疗法 (TT) 有效。通过查询“ARCA”数据库，通过试验模拟策略来检验这一假设。方法 接受 2NRTI 加蛋白酶抑制剂或非 NRTI 治疗的 HIV 感染者，转用 DT 或多替拉韦为基础的 TT，从首次 HIV-RNA < 50 cps/mL（基线）到病毒学失败（VF）进行随访。 ，即连续2个HIV-RNA≥50 cps/ml或1个HIV-RNA≥200 cp/mL)。那些在 6 个月内转为 DT 的患者被分配到“治疗”组，所有其他患者被分配到“对照”组。每个参与者也被克隆，分配给相反的策略，并在偏离该策略时进行审查。通过使用审查权重逆概率 (IPCW)-Cox 回归模型，我们计算了 DT 与 TT 的 VF 风险比，并根据 RAM 的存在进行分层。结果 总体而言，对 626 人进行了分析（204 人接受 DT，422 人接受 TT；73% 为男性，平均年龄 44 岁）。 DT 和 TT 分别发生 10 例和 31 例室颤，中位时间为 5.8 年。与完全活性 TT 相比，当在历史基因型中确认完全易感性时，DT 具有相似的疗效（aHR：0.88，95% CI 0.29-2.61；p=0.812）。当两组中均存在既往 M184V/I 时，DT 的 VF 风险较高，但无统计学意义（与 TT 相比，aHR 3.06，95% CI 0.45-20.84；p=0.252）。结论 与基于多替拉韦的 TT 相比，DT 与 VF 风险的统计学显着升高无关。