Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland.
Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland; University of Basel, Basel, Switzerland; SolidarMed, Partnerships for Health, Maseru, Lesotho.
Lancet Glob Health. 2024 Aug;12(8):e1312-e1322. doi: 10.1016/S2214-109X(24)00183-9.
Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT.
The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed.
Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study.
GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART.
Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation.
For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.
接受抗逆转录病毒疗法（ART）的儿童和青少年艾滋病毒感染者病毒血症发生率较高。我们评估了在莱索托和坦桑尼亚这两个几乎无法获得基因耐药检测（GRT）的国家，进行 GRT 以指导后续治疗是否能改善治疗结局。
基因型指导与经验性管理病毒血症（GIVE MOVE）是一项开放性、平行组随机对照试验，招募了年龄在 6 个月至 19 岁之间、正在接受 ART 治疗且病毒载量至少为 400 拷贝/mL 的 HIV 感染者。参与者是从莱索托和坦桑尼亚的 10 个临床中心和医院招募的。参与者通过电子随机分配，1:1 接受 GRT 加专家建议（GRT 组）或重复病毒载量检测和经验性的后续治疗（常规护理组）。参与者和研究人员未设盲，但终点委员会和进行病毒载量检测的实验室工作人员设盲。两组参与者均至少接受 3 次强化依从性咨询，GRT 组在入组时抽取血液进行 Sanger 测序评估 GRT。改良意向治疗人群的复合主要终点是死亡、住院、新出现的世卫组织 HIV 临床 4 期事件或在 36 周时未记录到低于 50 拷贝/mL 的病毒抑制，排除了在随机分组后被回溯发现不符合条件的参与者。严重不良事件在改良意向治疗人群中进行分析。该试验在 ClinicalTrials.gov （NCT04233242）注册，试验状态已完成。
2020 年 3 月 3 日至 2022 年 7 月 5 日，共纳入 286 名参与者，其中 284 名参与者纳入改良意向治疗分析（GRT 组 144 名，常规护理组 140 名）。这些参与者中，158 名（56%）为女性，126 名（44%）为男性。5 名（3%）GRT 组和 4 名（3%）常规护理组未完成随访，但纳入主要分析。两组的中位年龄均为 14 岁（IQR 9-16）。GRT 组有 67 名（47%）参与者和常规护理组有 73 名（52%）参与者发生复合主要终点（校正比值比 0·79 [95%CI 0·49 至 1·27]；校正风险差 -0·06 [95%CI -0·17 至 0·06]；p=0·34）；所有达到复合主要终点的参与者在 36 周时均未记录到病毒抑制。未记录到死亡病例，只有 1 例需要住院的 4 期临床事件（在常规护理组）；这是该研究中唯一记录到的严重不良事件。
在接受 ART 的病毒血症儿童和青少年中，GRT 指导管理并没有显著改善治疗结局。
博特纳基金会、瑞士国家科学基金会和戈特弗里德和朱莉娅·班格特-里纳基金会。
