Dipartimento di Sicurezza e Bioetica, Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
UOC Medicina Protetta-Malattie Infettive-ASL Viterbo, 0100 Viterbo, Italy.
Viruses. 2023 Mar 16;15(3):762. doi: 10.3390/v15030762.
Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype.
The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype.
A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs (8.4 in 100 patient-years follow-up, PYFU) and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33; = 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27; = 0.001), after adjusting for age, gender, baseline CD4 count and HIV-RNA, concurrent AIDS-defining event and months since HIV diagnosis. Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B (aHR 3.35; = 0.011), C (aHR 8.10; = 0.005), CRF02-AG (aHR 5.59; = 0.006) and G (aHR 13.90; < 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24; = 0.035) and CRF01-AE (versus B; aHR 10.65; = 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF.
In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone.
在随机试验中，基于多替拉韦（DTG）的一线治疗方案比基于达芦那韦（DRV）的方案显示出更优的疗效。我们在临床实践中比较了这两种策略，特别是考虑了治疗前药物耐药突变（DRMs）和 HIV-1 亚型的作用。
多中心抗逆转录病毒耐药性队列分析（ARCA）数据库被用来确定 2013 年至 2019 年期间开始使用 2NRTIs 加 DTG 或 DRV 进行一线治疗的 HIV-1 阳性患者。只选择了在治疗前进行基因耐药性测试（GRT）且 HIV-1 RNA≥1000 拷贝/mL 的成年（≥18 岁）患者。通过多变量 Cox 回归，我们在考虑治疗前 DRMs 和病毒亚型的情况下，比较了基于 DTG 和 DRV 的方案在病毒学失败（VF）时间上的差异。
共纳入 649 例患者，分别有 359 例（55.3%）和 290 例（44.7%）开始使用 DRV 和 DTG。在中位随访 11 个月期间，DRV 和 DTG 组分别有 41 例（8.4 例/100 患者年随访，PYFU）和 15 例（5.3 例/100 PYFU）发生 VF。与完全有效的 DTG 为基础的方案相比，DRV 治疗的 VF 风险更高（aHR 2.33； = 0.016），并且对于治疗前针对骨干的 DRMs 的 DTG 为基础的方案，风险更高（aHR 17.27； = 0.001），调整了年龄、性别、基线 CD4 计数和 HIV-RNA、并发 AIDS 定义性事件和 HIV 诊断后时间。与携带 B 型病毒亚型且接受 DTG 为基础方案治疗的患者相比，接受 DRV 治疗的患者在 B 型（aHR 3.35； = 0.011）、C 型（aHR 8.10； = 0.005）、CRF02-AG（aHR 5.59； = 0.006）和 G 型（aHR 13.90； < 0.001）中 VF 的风险增加；DTG 也显示在 C 型（与 B 型相比，aHR 10.24； = 0.035）和 CRF01-AE（与 B 型相比，aHR 10.65； = 0.035）中疗效降低。较高的基线 HIV-RNA 和较长的 HIV 诊断后时间也预示着 VF 的发生。
与随机试验一致，基于 DTG 的一线治疗方案总体上显示出比基于 DRV 的方案更优的疗效。GRT 可能仍然在识别更易发生 VF 的患者和指导抗逆转录病毒骨干药物的选择方面发挥作用。
