Della Negra Marinella, De Carvalho Aroldo Prohmann, De Aquino Maria Zilda, Pinto Jorge Andrade, Da Silva Marcos Tadeu Nolasco, Andreatta Kristen N, Graham Bryan, Liu Ya-Pei, Quirk Erin K
From the *Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; †Hospital Infantil Joana de Gusmão, Hospital DIA - Agronômica, Florianópolis, Brazil; ‡Instituto da Criança do Hospital das Clínicas da FMUSP, São Paulo, Brazil; §Faculdade de Medicina, UFMG, Belo Horizonte, Brazil; ¶Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil; ‖Gilead Sciences, Foster City, California; and **Gilead Sciences, Cambridge, United Kingdom.
Pediatr Infect Dis J. 2015 Apr;34(4):398-405. doi: 10.1097/INF.0000000000000649.
Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321).
HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients.
Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline.
Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.
关于富马酸替诺福韦二吡呋酯（TDF）长期治疗HIV感染青少年的报道有限。我们公布了GS-US-104-0321（研究321）随机、安慰剂（PBO）对照、双盲阶段之后的开放标签（OL）TDF扩展研究的最终结果。
接受TDF 300mg或PBO并采用优化背景治疗方案（OBR）治疗24至48周的12至17岁HIV感染青少年，随后在一项单臂研究扩展中接受OL TDF加OBR治疗。对所有接受TDF治疗的患者评估HIV-1 RNA水平及安全性，包括骨矿物质密度（BMD）。
81名受试者接受了TDF治疗（中位疗程96周）。没有受试者因安全性/耐受性问题死亡或停用OL TDF。在第144周时，HIV-1 RNA<50拷贝/mL的比例在最初随机接受TDF治疗且基线HIV-1 RNA>1000拷贝/mL的23名受试者中有30.4%（7名），在从PBO换用TDF且HIV-1 RNA<1000拷贝/mL的12名受试者中有41.7%（5名），而在随机接受PBO加OBR治疗失败且HIV-1 RNA>1000拷贝/mL并从PBO换用TDF的2名受试者中为0%（0名）。1名受试者出现对TDF的病毒耐药。在第144周时，估计肾小球滤过率的中位数下降为38.1 mL/min/1.73m²（n = 25）。在第144周时观察到脊柱BMD中位数增加（+12.70%，n = 26），全身除头部外BMD中位数增加（+4.32%，n = 26），以及身高年龄校正Z评分增加（n = 21；脊柱为+0.457，全身除头部外为+0.152）。81名受试者中有5名（6%）的BMD较基线持续下降>4%。
一些受试者对TDF加OBR有病毒学反应，且TDF耐药罕见。TDF耐受性良好，可考虑用于治疗HIV感染的青少年。
