ViiV Healthcare, Durham, North Carolina, USA.
Department of Pediatrics and Child Health, Children's Infectious Diseases Clinical Research Unit, Stellenbosch University, Tygerberg, South Africa.
AIDS Res Hum Retroviruses. 2024 Oct;40(10):606-613. doi: 10.1089/AID.2024.0020. Epub 2024 Jul 19.
APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4 cell count was 1,235 cells/mm [ = 51] at baseline, 1,690 cells/mm ( = 41) at Week 48, and 1,280 cells/mm ( = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.
APV20002 是一项多中心、国际性、开放性标签研究，于 2003 年开始，旨在研究利托那韦增强的福沙那韦（FPV/r）口服溶液（OS）与基于核苷逆转录酶抑制剂的抗逆转录病毒疗法（ART）联合用于治疗 4 周至<2 岁的 HIV-1 感染者的药代动力学、疗效和安全性，主要终点为第 48 周（48W）。APV20002 中的参与者可以在 48W 后继续在研究中，直到他们所在国家/地区可以获得 FPV OS。如果儿童体重超过>39 公斤或 FPV OS 没有临床获益，则需要停药。共有 59 名参与者入组；5/59 名接受了单次 FPV OS 访视以进行药代动力学测定。大多数（38/54；70%）为抗逆转录病毒经验者；39/59 名参与者接受了>48 周的治疗，其中 4/39 名因不良事件（AE）在 48 周后停药。48W 时，88%的参与者的 HIV-1 RNA<400 拷贝/mL（Observed 分析）；在第 684 周时，HIV-1 RNA<400 拷贝/mL 的比例仍保持较高（84%-100%）。基线时的中位 CD4 细胞计数为 1,235 个细胞/mm[=51]，第 48 周时为 1,690 个细胞/mm（=41），第 180 周时为 1,280 个细胞/mm（=21）。从基线到第 684 周，54/59（92%）名参与者无论因果关系如何，均至少发生了 1 次治疗出现的 AE；42/59（71%）发生了治疗出现的 2-4 级 AE，主要是最大毒性：2 级；21/59（36%）和 21/59（36%）发生了严重或 3/4 级 AE。从基线到第 684 周，14/54（26%）名参与者符合病毒学失败（VF）标准，9/14 名在 48W 前符合。9/14 名 VF 患者中有 1 名在 48W 时出现了治疗出现的对 FPV 的耐药性，1 名出现了对拉米夫定/恩曲他滨的耐药性。48W 后，5 名 VF 参与者中有 4 名进行了表型检测；所有参与者在 VF 时对所有研究药物仍敏感。总之，FPV OS 为基础的 ART 在这项长期儿科研究中至 684 周的治疗中具有疗效，并且通常耐受性良好，安全性与成人和较大儿童的经验一致。
