[接受齐多夫定治疗且未出现HIV感染进展的患者的频率及特征]

[Frequency and characteristics of patients treated with zidovudine and absence of progression of HIV infection].

作者信息

Soriano V, Heredia A, Mas A, Vallejo A, Garćia-Lerma G, Bravo R, Gómez-Cano M, Villalba N, Moreno V, Laguna F, Valencia E, Martínez P, González-Lahoz J

机构信息

Servicio de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid.

出版信息

An Med Interna. 1997 Jun;14(6):282-5.

PMID:9410098

Abstract

BACKGROUND

the efficacy of zidovudine (ZDV) is lost in many treated individuals after a few weeks or months of monotherapy. The development of drug resistance seems to explain this adverse event. However, some individuals seem to persistently benefit clinically and immunologically from ongoing ZDV monotherapy. The degree and causes of this phenomenon remain unclear.

PATIENTS AND METHODS

we studied 280 HIV-infected patients who have been receiving ZDV monotherapy for more than 18 months (mean 28 +/- 7 months), and whom has a CD4+ count between 200 and 500 x 10(6)/l at baseline. We classified them into two groups: Non-progressors with ZDV (NP-ZDV), subjects with an increase or a reduction < 15% in the CD4+ count; and Progressors with ZDV (P-ZDV), subjects showing a decline in the CD4 count > 15%. Epidemiological, immunological and virological features of each group were compared.

RESULTS

the prevalence of NP-ZDV in this population was 15.7% (44/280). Age, gender, and risk behaviour were not significantly different in NP-ZDV and P-ZDV. Although the CD4/CD8 ratio, as well as the CD45R0/CD45RA ratio into the CD4+ subpopulation, were higher in NP-ZDV than in P-ZDV, the values did not achieve statistical significance. Virological studies were performed on 36 (81.8%) NP-ZDV and 55 (23.3%) P-ZDV. Mean HIV-RNA titer was higher in P-ZDV than in NP-ZDV (8.4 x 10(4) vs. 1.5 x 10(3) copies/ml; p < 0.01). Virus isolation from circulating mononuclear cells was made more frequently in P-ZDV than in NP-ZDV (90.9% vs. 81.5%), although it did not achieve statistical significance. The syncitium-inducing (SI) phenotype was detected in more than a quarter (27.3%) of P-ZDV but was absent in NP-ZDV (p < 0.01). The prevalence of RT mutations at codon 215 was much lower in NP-ZDV than in P-ZDV, and it showed a strong statistical significance (13.9% vs. 74.5%; p < 0.01).

CONCLUSIONS

prolonged (> 2 years) lack of immunological and clinical progression can be observed in 15% of HIV-infected persons with mild immunosuppression, undertaking ZDV monotherapy. This effect seems to be associated with a characteristic virological profile, in which a low viral load, the absence of SI phenotype, and a lack of development of ZDV-resistance are the most relevant features.

摘要

背景

许多接受齐多夫定（ZDV）单药治疗的患者在几周或几个月后会失去其疗效。耐药性的产生似乎可以解释这一不良事件。然而，一些患者似乎在持续的ZDV单药治疗中在临床和免疫方面持续获益。这一现象的程度和原因仍不清楚。

患者与方法

我们研究了280例接受ZDV单药治疗超过18个月（平均28±7个月）且基线时CD4 +细胞计数在200至500×10⁶ /L之间的HIV感染患者。我们将他们分为两组：ZDV治疗无进展者（NP-ZDV），即CD4 +细胞计数增加或减少<15%的患者；以及ZDV治疗进展者（P-ZDV），即CD4细胞计数下降>15%的患者。比较了每组的流行病学、免疫学和病毒学特征。

结果

该人群中NP-ZDV的患病率为15.7%（44/280）。NP-ZDV组和P-ZDV组在年龄、性别和危险行为方面无显著差异。尽管NP-ZDV组的CD4/CD8比值以及CD4 +亚群中的CD45R0/CD45RA比值高于P-ZDV组，但这些值未达到统计学显著性。对36例（81.8%）NP-ZDV患者和55例（23.3%）P-ZDV患者进行了病毒学研究。P-ZDV组的平均HIV-RNA滴度高于NP-ZDV组（8.4×10⁴对1.5×10³拷贝/毫升；p<0.01）。P-ZDV组从循环单核细胞中分离病毒的频率高于NP-ZDV组（90.9%对81.5%），尽管未达到统计学显著性。超过四分之一（27.3%）的P-ZDV患者检测到合胞体诱导（SI）表型，而NP-ZDV患者中未检测到（p<0.01）。NP-ZDV组中密码子215处RT突变的患病率远低于P-ZDV组，且具有很强的统计学显著性（13.9%对74.5%；p<0.01）。