Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.
Pediatr Infect Dis J. 2012 May;31(5):469-73. doi: 10.1097/INF.0b013e31824bf239.
There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents.
A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.8 mg/m(2)) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at week 24
Eighty-seven subjects (45 TDF, 42 placebo) received the study drug. Through week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log(10)copies/mL, P = 0.55). The percentages of subjects who achieved HIV-1 RNA <400 copies/mL were similar at week 24 (40.9 versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4 versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9 versus 33.3%). TDF was generally safe and well tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the 2 groups.
This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.
目前，关于替诺福韦酯（TDF）在感染 HIV-1 的青少年患者中的安全性和抗病毒活性的数据较少。
进行了一项随机、双盲、安慰剂对照研究。90 名（12 至 <18 岁）正在接受抗逆转录病毒治疗且病毒载量阳性的青少年被随机分为 TDF 组（300mg，平均 216.8mg/m2）或安慰剂组，两组均联合优化背景治疗方案（OBR）治疗 48 周。主要疗效终点为第 24 周时与基线相比血浆 HIV-1 RNA 的时间加权平均变化。
87 名受试者（45 名 TDF，42 名安慰剂）接受了研究药物治疗。至第 24 周时，TDF 组和安慰剂组的血浆 HIV-1 RNA 的时间加权平均变化中位数无差异（-1.6 与 -1.6log10 拷贝/mL，P=0.55）。第 24 周时，HIV-1 RNA<400 拷贝/mL 的受试者比例在两组中相似（40.9%比 41.5%）。TDF 组和安慰剂组各有 25%的受试者（24.4%比 28.6%）的 OBR 中有至少 3 种活性药物。两组均有较多受试者对 TDF 存在基线基因型耐药（48.9%比 33.3%）。TDF 通常安全且耐受良好。两组间肾功能和骨矿物质密度的变化无统计学显著差异。
该研究未能达到其主要和次要疗效终点，即替诺福韦酯联合 OBR 治疗有抗逆转录病毒治疗史的青少年患者。OBR 的疗效和两组受试者对 TDF 的基线基因型耐药可能使疗效结果产生偏倚。在该青少年人群中未观察到与 TDF 相关的具有临床意义的肾毒性或骨毒性。
