Balestre Eric, Dupon Michel, Capdepont Sophie, Thiébaut Rodolphe, Boucher Sébastien, Fleury Hervé, Dabis François, Masquelier Bernard
INSERM U593, Université Victor Segalen, Bordeaux, France.
J Clin Virol. 2006 Jun;36(2):95-9. doi: 10.1016/j.jcv.2006.02.002. Epub 2006 Mar 23.
HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTI)-only based, comprising tenofovir DF(TDF) have been shown to lead to high rates of virological failures (VF), mainly in patients on first-line combination therapy. We wished to investigate the virological response to these regimens in a large cohort of antiretroviral (ARV)-treated patients.
Patients followed-up in the Aquitaine Cohort in 2001-2003 and who had received NRTI-based, TDF-including regimens for at least 3 months were included. The VF was defined as: (i) a decrease in plasma HIV-1 RNA <0.5 log(10)copies/ml between M0 and M3; or (ii) a plasma HIV-1 RNA >50 copies/ml at M3 in patients with plasma HIV-1 RNA <50 copies/ml at M0. The baseline RT genotype was determined in a subgroup of patients.
Within 121 patients (95% ARV-experienced) who received either lamivudine (3TC)/didanosine (DDI)/TDF (n=48), or abacavir (ABC)/3TC/TDF (n=14), or 3TC/zidovudine (ZDV)/TDF (n=27), or 3TC/ZDV/ABC/TDF (n=20), or DDI/ABC/TDF (n=12), the ABC/3TC/TDF and DDI/ABC/TDF combinations were associated with the highest frequencies of VF. In contrast the use of ZDV was related to a better virological response. The baseline RT genotype was also predictive of the virological outcome.
NRTI-based, TDF-including therapies can lead to high rates of VF both in ARV-naïve and in ARV-experienced patients. Our data strongly suggest the interest of associating ZDV and TDF in these regimens.
仅基于HIV-1核苷/核苷酸逆转录酶抑制剂(NRTI),包含替诺福韦酯(TDF)的治疗方案已显示出较高的病毒学失败率(VF),主要发生在接受一线联合治疗的患者中。我们希望在一大群接受抗逆转录病毒(ARV)治疗的患者中研究这些治疗方案的病毒学反应。
纳入2001年至2003年在阿基坦队列中接受随访且接受基于NRTI、包含TDF的治疗方案至少3个月的患者。病毒学失败定义为:(i)在M0和M3之间血浆HIV-1 RNA下降<0.5 log(10)拷贝/毫升;或(ii)M0时血浆HIV-1 RNA<50拷贝/毫升的患者在M3时血浆HIV-1 RNA>50拷贝/毫升。在一组亚组患者中确定基线RT基因型。
在121例患者(95%有ARV治疗经验)中,这些患者接受了拉米夫定(3TC)/去羟肌苷(DDI)/TDF(n = 48)、或阿巴卡韦(ABC)/3TC/TDF(n = 14)、或3TC/齐多夫定(ZDV)/TDF(n = 27)、或3TC/ZDV/ABC/TDF(n = 20)、或DDI/ABC/TDF(n = 12)治疗,其中ABC/3TC/TDF和DDI/ABC/TDF组合的病毒学失败频率最高。相比之下,使用ZDV与更好的病毒学反应相关。基线RT基因型也可预测病毒学结果。
基于NRTI、包含TDF的治疗方案在初治和有ARV治疗经验的患者中均可导致较高的病毒学失败率。我们的数据强烈表明在这些治疗方案中联合使用ZDV和TDF是有益的。