替诺福韦酯治疗抗逆转录病毒治疗失败的HIV-1感染青少年的长期疗效和安全性：GS-US-104-0321研究的最终结果

Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321.

作者信息

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

机构信息

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.

出版信息

Pediatr Infect Dis J. 2015 Apr;34(4):398-405. doi: 10.1097/INF.0000000000000649.

DOI:10.1097/INF.0000000000000649

PMID:25599284

Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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。

方法

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）。

结果

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%。