Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medical Sciences, Infectious and Tropical Diseases Unit, AOU Senese, Siena, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Int J Antimicrob Agents. 2022 Sep;60(3):106636. doi: 10.1016/j.ijantimicag.2022.106636. Epub 2022 Jul 9.
Despite the wide use of single-tablet regimens (STRs), few real-life data are available regarding the impact of pre-existent drug resistance on virological failure (VF). We aimed to fill this gap by analysing a large cohort of individuals selected from the ARCA database. The impact on VF of pre-existent resistance-associated mutations (RAMs) and cumulative genotypic susceptibility score (cGSS) before STR start was evaluated through survival analysis. Potential emergence of resistance at VF was also evaluated. Overall, 3916 individuals were included, comprising 678 treatment-naïve (G1), 2309 treatment-experienced aviraemic (G2) and 929 viraemic (G3), of whom 65.2% were treated with a STR based on efavirenz (35.2%) or rilpivirine (30.0%). At 2 years after starting a STR, the overall probability of VF was 5.9% in G1, 8.7% in G2 and 20.8% in G3. No impact of pre-existent resistance on VF was found in G1. The probability of VF was higher in patients with cGSS < 3 (reduced susceptibility to at least one drug) than in those with cGSS = 3 (full susceptibility to STR drugs) both in G2 and G3. A higher probability of VF was also found in the presence of pre-existent M184V (alone or in combination with pre-existent thymidine analogue mutations). Among patients who failed STR, a significant emergence of RAMs was found only in those exposed to EFV/FTC/TDF in G3 (specifically K103N and M184V). Our results confirm a high efficacy of STRs in clinical settings. Pre-existent resistance appears to influence virological efficacy of STRs in treatment-experienced individuals (both aviraemic and viraemic).
尽管单一片剂方案（STRs）得到了广泛应用，但关于预先存在的耐药性对病毒学失败（VF）的影响，几乎没有真实世界的数据。我们旨在通过分析从 ARCA 数据库中选择的大量个体来填补这一空白。通过生存分析评估 STR 开始前预先存在的耐药相关突变（RAMs）和累积基因型易感性评分（cGSS）对 VF 的影响。还评估了潜在的耐药性在 VF 时的出现。总体而言，纳入了 3916 名个体，包括 678 名治疗初治（G1）、2309 名治疗经验丰富的艾滋病毒血症（G2）和 929 名病毒血症（G3），其中 65.2%接受了基于依非韦伦（35.2%）或利匹韦林（30.0%）的 STR 治疗。在开始 STR 治疗后 2 年，G1 中 VF 的总体概率为 5.9%，G2 为 8.7%，G3 为 20.8%。在 G1 中，预先存在的耐药性对 VF 没有影响。在 G2 和 G3 中，cGSS<3（对至少一种药物的敏感性降低）的患者比 cGSS=3（对 STR 药物的完全敏感性）的患者 VF 的概率更高。在存在预先存在的 M184V（单独存在或与预先存在的胸苷类似物突变联合存在）的情况下，VF 的概率也更高。在 STR 失败的患者中，仅在 G3 中暴露于 EFV/FTC/TDF 的患者中发现了明显的 RAM 出现（具体为 K103N 和 M184V）。我们的结果证实 STR 在临床环境中的高效性。预先存在的耐药性似乎影响了治疗经验丰富的个体（艾滋病毒血症和病毒血症）对 STR 的病毒学疗效。
