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初治抗反转录病毒治疗的 HIV 感染者中,基线 HIV-1 嗜性对病毒学应答和 CD4 细胞计数增加的影响。

Impact of baseline HIV-1 tropism on viral response and CD4 cell count gains in HIV-infected patients receiving first-line antiretroviral therapy.

机构信息

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

出版信息

J Infect Dis. 2011 Jul 1;204(1):139-44. doi: 10.1093/infdis/jir218.

Abstract

BACKGROUND

Viral tropism influences the natural history of human immunodeficiency type 1 (HIV-1) disease: X4 viruses are associated with faster decreases in CD4 cell count. There is scarce information about the influence of viral tropism on treatment outcomes.

METHODS

Baseline plasma samples from patients recruited to the ArTEN (Atazanavir/ritnoavir vs. Nevirapine on a background of Tenofovir and Emtricitabine) trial were retrospectively tested for HIV-1 tropism using the genotypic tool geno2pheno(FPR=5.75%). ArTEN compared nevirapine with atazanavir-ritonavir, both along with tenofovir-emtricitabine, in drug-naïve patients.

RESULTS

Of 569 ArTEN patients, 428 completed 48 weeks of therapy; 282 of these received nevirapine and 146 of these received atazanavir-ritonavir. Overall, non-B subtypes of HIV-1 were recognized in 96 patients (22%) and X4 viruses were detected in 55 patients (14%). At baseline, patients with X4 viruses had higher plasma HIV RNA levels (5.4 vs 5.2 log copies/mL, respectively; P = .044) and lower CD4 cell counts (145 vs 188 cells/μL, respectively; P < .001) than those with R5 strains. At week 48, virologic responses were lower in patients with X4 viruses than in patients with R5 viruses (77% vs 92%, respectively; P = .009). Multivariate analysis confirmed HIV-1 tropism as an independent predictor of virologic response at week 24 (P = .012). This association was extended to week 48 (P = .007) in clade B viruses. Conversely, CD4 cell count recovery was not influenced by baseline HIV-1 tropism.

CONCLUSIONS

HIV-1 tropism is an independent predictor of virologic response to first-line antiretroviral therapy. In contrast, it does not seem to influence CD4 cell count recovery.

CLINICAL TRIALS REGISTRATION

NCT00389207.

摘要

背景

病毒嗜性影响人类免疫缺陷病毒 1 型(HIV-1)疾病的自然史:X4 病毒与 CD4 细胞计数更快下降有关。关于病毒嗜性对治疗结果的影响,信息很少。

方法

回顾性检测 ArTEN(阿扎那韦/利托那韦与奈韦拉平相比,在替诺福韦和恩曲他滨背景下)试验中招募的患者的基线血浆样本,使用基因型工具 geno2pheno(FPR=5.75%)检测 HIV-1 嗜性。ArTEN 在初治患者中比较了奈韦拉平与阿扎那韦-利托那韦,两者均与替诺福韦-恩曲他滨联合使用。

结果

在 569 名 ArTEN 患者中,428 名完成了 48 周的治疗;其中 282 名接受了奈韦拉平,146 名接受了阿扎那韦-利托那韦。总体而言,在 96 名患者(22%)中发现了非 B 型 HIV-1 亚型,在 55 名患者(14%)中检测到了 X4 病毒。基线时,X4 病毒患者的血浆 HIV RNA 水平更高(分别为 5.4 和 5.2 log 拷贝/mL;P=0.044),CD4 细胞计数更低(分别为 145 和 188 个/μL;P<0.001)。在第 48 周时,X4 病毒患者的病毒学应答低于 R5 病毒患者(分别为 77%和 92%;P=0.009)。多变量分析证实,在第 24 周时,HIV-1 嗜性是病毒学应答的独立预测因素(P=0.012)。这种关联在 B 型病毒中延伸到第 48 周(P=0.007)。相反,CD4 细胞计数的恢复不受基线 HIV-1 嗜性的影响。

结论

HIV-1 嗜性是一线抗逆转录病毒治疗病毒学应答的独立预测因素。相比之下,它似乎并不影响 CD4 细胞计数的恢复。

临床试验注册

NCT00389207。

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