Grant Philip M, Tierney Camlin, Budhathoki Chakra, Daar Eric S, Sax Paul E, Collier Ann C, Fischl Margaret A, Zolopa Andrew R, Balamane Maya, Katzenstein David
Division of Infectious Diseases, Stanford University, Palo Alto, California.
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
HIV Clin Trials. 2013 Nov-Dec;14(6):284-91. doi: 10.1310/hct1406-284.
ACTG A5202 randomized treatment-naïve individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC.
To compare regimen-specific early virologic response.
Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (N = 1,813) and from entry to week 1, 2, and 4 in substudy subjects (n = 179). We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional hazards models.
TDF/FTC and ABC/3TC produced similar week 4 VL declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median -2.1 vs -1.9 log10 copies/mL; P < .001). In the substudy of subjects with week 1, 2, and 4 VL data, there was no difference in VL decline in individuals randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller week 4 VL decline was associated with increased risk of virologic failure.
Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity.
ACTG A5202研究将初治个体随机分为接受替诺福韦-恩曲他滨（TDF/FTC）或阿巴卡韦-拉米夫定（ABC/3TC）联合依非韦伦（EFV）或阿扎那韦/利托那韦（ATV/r）治疗。高筛查病毒载量（VL）分层（≥100,000拷贝/mL）的个体使用ABC/3TC时病毒学失败率增加。
比较特定治疗方案的早期病毒学反应。
我们使用Wilcoxon秩和检验，比较了A5202研究受试者（N = 1,813）从入组到第4周以及子研究受试者（n = 179）从入组到第1、2和4周的特定治疗方案的VL变化。我们使用Cox比例风险模型评估第4周VL变化与病毒学失败时间之间的关联。
在整个研究人群和高VL分层中，TDF/FTC和ABC/3TC在第4周时VL下降情况相似。第4周时，EFV导致的VL从基线下降幅度大于ATV/r（中位数分别为-2.1对-1.9 log10拷贝/mL；P <.001）。在有第1、2和4周VL数据的受试者子研究中，随机接受TDF/FTC与ABC/3TC的个体在VL下降方面没有差异，但在这些时间点的每一个，EFV导致的VL从入组时下降幅度均大于ATV/r。第4周VL下降幅度较小与病毒学失败风险增加相关。
在所有治疗组中，第4周病毒学反应较弱与随后病毒学失败的较高风险相关。然而，第4周VL下降的治疗方案间差异与A5202研究中先前报道的长期病毒学疗效差异并不平行，这表明治疗方案间反应差异并非由于抗病毒活性的内在差异。
