喀麦隆HIV-1治疗失败后整合酶链转移抑制剂与第二代非核苷类逆转录酶抑制剂联合双重疗法的预测疗效：对低收入和中等收入国家长效治疗策略应用的启示

Predictive Efficacy of Dual Therapies Combining Integrase Strand Transfer Inhibitors with Second-Generation Non-Nucleoside Reverse Transcriptase Inhibitors Following HIV-1 Treatment Failure in Cameroon: Implications for the Use of a Long-Acting Therapeutic Strategy in Low- and Middle-Income Countries.

作者信息

Gouissi Anguechia Davy-Hyacinthe, Bouba Yagai, Semengue Ezechiel Ngoufack Jagni, Ka'e Aude Christelle, Takou Désiré, Ambe Chenwi Collins, Beloumou Grace, Nka Alex Durand, Basseck Wome Ulrich Roland, Santoro Maria Mercedes, Ceccherini-Silberstein Francesca, Chatté Adawaye, Montesano Carla, Cappelli Giulia, Colizzi Vittorio, Ndjolo Alexis, Mbanya Dora, Ndembi Nicaise, Perno Carlo-Federico, Fokam Joseph

机构信息

Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon.

Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé P.O. Box 337, Cameroon.

出版信息

Viruses. 2024 Nov 29;16(12):1853. doi: 10.3390/v16121853.

DOI:10.3390/v16121853

PMID:39772163

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11680099/

Abstract

Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients. We genotyped the HIV-1 gene using Sanger sequencing and assessed acquired RAMs to NNRTIs and INSTIs in patients failing treatment from March 2019 to December 2023. Drug susceptibility was interpreted using Stanford HIVdb v9.5, and statistical analyses were performed using SPSS v22. Of 130 successfully genotyped participants (median age (IQR): 38 (27-46) years; 59.2% female), 92.3% had RAMs to NNRTIs and 1.5% to INSTIs. Prevailing RAMs were Y181C (32.3%) among NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54% and 38.46% genotypic sensitivity, respectively. Among INSTIs, we found 97.69% efficacy for dolutegravir/bictegravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. The overall predictive efficacy of DT was lower among participants who failed 1st-Gen-NNRTI ( < 0.001); with etravirine + dolutegravir/bictegravir combination showing the highest score (43.8%). Conclusively, DT combining INSTIs + 2nd-Gen-NNRTIs might be suboptimal in the context of previous ART failure, especially with NNRTI-based treatment in low- and middle-income countries. The general data clearly indicate that without resistance testing, it is nearly impossible to use long-acting dual therapies in previously failing patients.

摘要

将整合酶链转移抑制剂（INSTIs）与第二代非核苷类逆转录酶抑制剂（2nd-Gen-NNRTIs）联合使用的双重疗法（DT）为改善艾滋病病毒（HIV）治疗的依从性提供了新的可能性。然而，对先前抗逆转录病毒药物的耐药相关突变（RAMs）可能会危及双重疗法的疗效。我们在此描述了喀麦隆患者治疗失败后INSTIs + 2nd-Gen-NNRTI联合双重疗法的预测疗效。我们使用桑格测序对HIV-1基因进行基因分型，并评估了2019年3月至2023年12月治疗失败患者中对非核苷类逆转录酶抑制剂和整合酶链转移抑制剂的获得性耐药相关突变。使用斯坦福HIVdb v9.5解释药物敏感性，并使用SPSS v22进行统计分析。在130名成功进行基因分型的参与者中（年龄中位数（四分位间距）：38（27 - 46）岁；59.2%为女性），92.3%对非核苷类逆转录酶抑制剂有耐药相关突变，1.5%对整合酶链转移抑制剂有耐药相关突变。常见的耐药相关突变在非核苷类逆转录酶抑制剂中为Y181C（32.3%），在整合酶链转移抑制剂中为R263K（0.7%）。在第二代非核苷类逆转录酶抑制剂中，依曲韦林、多拉韦林和利匹韦林的基因分型敏感性分别为43.85%、41.54%和38.46%。在整合酶链转移抑制剂中，我们发现多替拉韦/比克替拉韦的疗效为97.69%，卡博特韦为96.15%，埃替拉韦/拉替拉韦为92.31%。在第一代非核苷类逆转录酶抑制剂治疗失败的参与者中，双重疗法的总体预测疗效较低（<0.001）；依曲韦林 + 多替拉韦/比克替拉韦组合得分最高（43.8%）。总之，在先前抗逆转录病毒治疗失败的情况下，尤其是在低收入和中等收入国家基于非核苷类逆转录酶抑制剂的治疗中，INSTIs + 2nd-Gen-NNRTIs联合双重疗法可能并非最佳选择。总体数据清楚地表明，在没有耐药性检测的情况下，几乎不可能在先前治疗失败的患者中使用长效双重疗法。