Pharmacology Research Laboratories, University of Liverpool, Liverpool, UK.
HIV Med. 2009 Oct;10(9):527-35. doi: 10.1111/j.1468-1293.2009.00724.x.
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.
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.
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).
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.
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。
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。
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）。
这项系统的荟萃回归分析表明，与使用 ABC/3TC 相比，一线使用 TDF/FTC NRTI 骨架与增强 PI 联合治疗具有更高的疗效。然而，这种效果可能因试验之间在基线特征、患者管理或依从性方面的差异而受到影响。
