英国伦敦大学学院Alasdair Bamford团队研究了非洲感染艾滋病毒儿童的二线抗逆转录病毒治疗。这一研究成果发表在2025年5月15日出版的《新英格兰医学杂志》上。

感染人类免疫缺陷病毒（HIV）的儿童在二线抗逆转录病毒治疗（ART）方面的选择有限。

在这项2 × 4因子设计的开放标签试验中，研究组随机分配一线治疗失败的艾滋病毒儿童接受富马酸替诺福韦阿拉那胺（TAF）-恩曲他滨或标准治疗（阿巴卡韦或齐多夫定加拉米夫定）作为主干，多替重力韦或利托那韦增强的达那韦、阿扎那韦或洛匹那韦作为锚定药物。主要结果是96周时病毒载量低于400拷贝/毫升。研究人员假设TAF-恩曲他滨的疗效不低于标准治疗，多替格雷韦和利托那韦增强的达那韦的疗效均优于利托那韦增强的洛匹那韦和阿扎那韦联合分析，利托那韦增强的阿扎那韦的疗效不低于利托那韦增强的洛匹那韦。安全性也进行了评估。

共有919名儿童接受随机分组；458人接受TAF-恩曲他滨治疗，461人接受标准治疗。指定的锚定药物是多替格拉韦（229名受试者）、利托那韦增强的达那韦（232名受试者）、利托那韦增强的阿扎那韦（231名受试者）和利托那韦增强的洛匹那韦（227名受试者）。参与者的中位年龄为10岁，497名（54.1%）为男性。基线时的中位病毒载量为每毫升17573拷贝。

在第96周，TAF-恩曲他滨优于标准治疗：病毒载量低于400拷贝/毫升的参与者百分比的调整差异为6.3个百分点（95%置信区间，2.0至10.6；P = 0.004）。达那韦优于利托那韦增强的洛匹那韦和阿扎那韦联合分析（调整后的差异，9.7个百分点；95% CI, 4.8 - 14.5；P<0.001），但利托那韦增强的达那韦没有（调整后的差异，5.6个百分点；95% CI, 0.3 ~ 11.0；P = 0.04）。利托那韦增强的阿扎那韦不逊于利托那韦增强的洛匹那韦。1例儿童死亡，29例（3.2%）发生严重不良事件，组间差异无统计学意义。

研究结果表明，包括TAF-恩曲他滨和多替格拉韦的二线抗逆转录病毒治疗方案对儿童有效，没有安全问题的证据。利托那韦增强的达那韦也有效。

附：英文原文

Title: Second-Line Antiretroviral Therapy for Children Living with HIV in Africa

Author: Victor Musiime, Mutsa Bwakura-Dangarembizi, Alexander J. Szubert, Vivian Mumbiro, Hilda A. Mujuru, Cissy M. Kityo, Abbas Lugemwa, Katja Doerholt, Chishala Chabala, Shafic Makumbi, Veronica Mulenga, Helen McIlleron, David Burger, Eva Natukunda, Clare Shakeshaft, Kyomuhendo Jovia Linda, Kusum Nathoo, Lara Monkiewicz, Ibrahim Yawe, Monica Kapasa, Mary Nyathi, Joyce Lungu, Bwendo Nduna, Wedu Ndebele, Annabelle South, Mwate Mwamabazi, Godfrey Musoro, Anna Griffiths, Khozya Zyambo, Rashidah Nazzinda, Kevin Zimba, Yingying Zhang, Simon Walker, Anna Turkova, A. Sarah Walker, Alasdair Bamford, Diana M. Gibb

Issue&Volume: 2025-05-15

Abstract:

BACKGROUND

Children living with human immunodeficiency virus (HIV) have limited options for second-line antiretroviral therapy (ART).

METHODS

In this open-label trial with a 2-by-4 factorial design, we randomly assigned children with HIV who had first-line treatment failure to receive second-line therapy with tenofovir alafenamide fumarate (TAF)–emtricitabine or standard care (abacavir or zidovudine, plus lamivudine) as the backbone and dolutegravir or ritonavir-boosted darunavir, atazanavir, or lopinavir as the anchor drug. The primary outcome was a viral load of less than 400 copies per milliliter at 96 weeks. We hypothesized that TAF–emtricitabine would be noninferior to standard care, that dolutegravir and ritonavir-boosted darunavir would each be superior to ritonavir-boosted lopinavir and atazanavir analyzed in combination, and that ritonavir-boosted atazanavir would be noninferior to ritonavir-boosted lopinavir. Safety was also assessed.

RESULTS

A total of 919 children underwent randomization; 458 were assigned to receive TAF–emtricitabine, and 461 to receive standard care. Assigned anchor drugs were dolutegravir (229 participants), ritonavir-boosted darunavir (232), ritonavir-boosted atazanavir (231), and ritonavir-boosted lopinavir (227). The median age of participants was 10 years, and 497 (54.1%) were male. The median viral load at baseline was 17,573 copies per milliliter. At week 96, TAF–emtricitabine was superior to standard care: the adjusted difference in the percentage of participants with a viral load of less than 400 copies per milliliter was 6.3 percentage points (95% confidence interval [CI], 2.0 to 10.6; P=0.004). Dolutegravir was superior to ritonavir-boosted lopinavir and atazanavir analyzed in combination (adjusted difference, 9.7 percentage points; 95% CI, 4.8 to 14.5; P<0.001), but ritonavir-boosted darunavir was not (adjusted difference, 5.6 percentage points; 95% CI, 0.3 to 11.0; P=0.04 [prespecified threshold, P=0.03]). Ritonavir-boosted atazanavir was noninferior to ritonavir-boosted lopinavir. One child died, and 29 (3.2%) had serious adverse events, with no significant between-group differences.

CONCLUSIONS

Second-line ART regimens including TAF–emtricitabine and dolutegravir were effective for children, with no evidence of safety concerns. Ritonavir-boosted darunavir was also effective.

DOI: NJ202505153921909

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2404597