核苷类逆转录酶抑制剂骨架对基于蛋白酶抑制剂的一线强化高效抗逆转录病毒治疗疗效的影响：5168 例患者 12 项临床试验的荟萃回归分析。

Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patients.

机构信息

Pharmacology Research Laboratories, University of Liverpool, Liverpool, UK.

出版信息

HIV Med. 2009 Oct;10(9):527-35. doi: 10.1111/j.1468-1293.2009.00724.x.

DOI:10.1111/j.1468-1293.2009.00724.x

PMID:19785663

Abstract

OBJECTIVES

Tenofovir/emtricitabine (TDF/FTC) and abacavir/lamivudine (ABC/3TC) are widely used with ritonavir (RTV)-boosted protease inhibitors (PIs) as first-line highly active antiretroviral therapy (HAART), but there is conflicting evidence on their relative efficacy. The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones.

METHODS

A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 5168 antiretroviral-naïve patients, where TDF/FTC (n=3399) or ABC/3TC (n=1769) was used with RTV-boosted PI. For each NRTI backbone and RTV-boosted PI, the percentage of patients with viral load <50 HIV-1 RNA copies/mL at week 48 by standardized Intent to Treat, Time to Loss of Virological Failure (ITT TLOVR) analysis were combined using inverse-variance weighting. The effect of baseline HIV RNA, CD4 cell count and choice of NRTI backbone were examined using a weighted analysis of covariance.

RESULTS

Across all the trials, HIV RNA suppression rates were significantly higher for those with baseline viral load below 100,000 copies/mL (77.2%) vs. above 100,000 copies/mL (70.9%) (P=0.0005). For the trials of lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r) and fosamprenavir/ritonavir (FAPV/r) using either TDF/FTC or ABC/3TC, the HIV RNA responses were significantly lower when ABC/3TC was used, relative to TDF/FTC, for all patients (P=0.0015) and for patients with baseline viral load <100,000 copies/mL (70.1%vs. 80.6%, P=0.0161), and was borderline for those with viral load >100,000 copies/mL (67.5%vs. 71.5%, P=0.0523).

CONCLUSIONS

This systematic meta-regression analysis suggests higher efficacy for first-line use of a TDF/FTC NRTI backbone with boosted PIs, relative to use of ABC/3TC. However, this effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence.

摘要

目的

替诺福韦/恩曲他滨（TDF/FTC）和阿巴卡韦/拉米夫定（ABC/3TC）与利托那韦（RTV）增强蛋白酶抑制剂（PI）联合广泛用于一线高效抗逆转录病毒治疗（HAART），但关于它们相对疗效的证据相互矛盾。ACTG 5202 和 BICOMBO 试验表明 TDF/FTC 的疗效更高，而 HEAT 试验则表明核苷逆转录酶抑制剂（NRTI）骨架之间无疗效差异。

方法

通过系统的 MEDLINE 搜索，在 12 项临床试验的 5168 名抗逆转录病毒初治患者中确定了 21 个治疗组，其中 3399 名患者使用 TDF/FTC，1769 名患者使用 ABC/3TC，与 RTV 增强 PI 联合使用。对于每个 NRTI 骨架和 RTV 增强 PI，通过标准化的意向治疗、病毒学失败时间（ITT TLOVR）分析，将 48 周时病毒载量<50 HIV-1 RNA 拷贝/mL 的患者百分比合并使用逆方差加权法。使用加权协方差分析检查基线 HIV RNA、CD4 细胞计数和 NRTI 骨架选择的影响。

结果

在所有试验中，基线病毒载量低于 100,000 拷贝/mL 的患者（77.2%）与高于 100,000 拷贝/mL 的患者（70.9%）相比，HIV RNA 抑制率显著更高（P=0.0005）。对于使用洛匹那韦/利托那韦（LPV/r）、阿扎那韦/利托那韦（ATV/r）和福沙那韦/利托那韦（FAPV/r）的试验，对于所有患者（P=0.0015）和基线病毒载量<100,000 拷贝/mL 的患者（70.1%比 80.6%，P=0.0161），与 TDF/FTC 相比，使用 ABC/3TC 时 HIV RNA 反应显著较低，对于病毒载量>100,000 拷贝/mL 的患者，这一结果具有边缘意义（67.5%比 71.5%，P=0.0523）。