Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London, UK.
Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
HIV Med. 2021 Sep;22(8):770-774. doi: 10.1111/hiv.13118. Epub 2021 May 8.
Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study.
At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively.
Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization.
Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.
对于基线病毒载量较高的个体，如原发性 HIV-1 感染（PHI）患者，快速启动抗逆转录病毒治疗（ART）非常重要。有时会考虑使用四药方案；然而，关于其耐受性的数据尚缺乏。本研究旨在评估在 HIV-1 储库研究中消除病毒（RIVER）研究中使用的四药方案的耐受性。
在入组时，ART 初治的成年参与者或新开始 ART 的患者，在 PHI 确诊前≤7 天内，在 4 周内开始或强化至四药方案。快速启动定义为确诊前或确诊后≤7 天。主要和次要结局分别为通过 7 天回顾法测量的患者报告的依从性和入组至随机化之间的方案转换。
共有 54 名男性被纳入研究：72.2%为白种人，中位年龄为 32 岁，42.6%的病毒载量≥100000 HIV-1 RNA 拷贝/ml，92.6%的感染途径为男男性行为。20 名（37%）开始四药方案，34 名（63%）方案强化。快速启动 ART 的比例为 37%，100%的患者在 4 周内开始治疗。第 4、12、24 周时，分别有 37.0%、69.0%和 94.0%的患者病毒载量不可测（＜50 拷贝/ml）。分别有 88.9%、87.0%、82.4%和 94.1%的患者在第 4、12、22 和 24 周报告了 100%的依从率。有 5 名患者转为三药方案，4 名患者改变了方案组成，2 名患者在随机化后改变了方案。
总体而言，四药方案具有良好的耐受性和较高的依从性。虽然四药方案相对于三药方案的益处尚不清楚，但如果临床需要暂时强化治疗以帮助促进治疗，我们的研究结果应该可以提供一些保证。
