齐多夫定-拉米夫定联合疗法用于未接受过抗逆转录病毒治疗的垂直感染艾滋病毒儿童的初步研究。

Pilot study of zidovudine-lamivudine combination therapy in vertically HIV-infected antiretroviral-naive children.

作者信息

Horneff G, Adams O, Wahn V

机构信息

Department of Paediatrics, Institute of Medical Microbiology and Virology, Heinrich Heine University, Düsseldorf, Germany.

出版信息

AIDS. 1998 Mar 26;12(5):489-94. doi: 10.1097/00002030-199805000-00010.

DOI:10.1097/00002030-199805000-00010

PMID:9543447

Abstract

OBJECTIVE

To examine tolerance and efficacy of a zidovudine plus lamivudine combination in HIV-infected children without previous exposure to antiretroviral drugs.

METHODS

Thirteen vertically infected children (aged 4 months to 10 years) were treated with zidovudine (approximately 100 mg/m2 three times daily) and lamivudine (4 mg/kg twice daily). CD4 T-cell count, plasma HIV RNA concentration, complete blood count and blood chemistry profile were monitored before treatment and at months 1, 3 and 6.

RESULTS

In general, treatment was well tolerated. One child developed slight neutropenia in the presence of antineutrophil antibodies. CD4 cell count increased from 851+/-621 x 10(6)/l at baseline to 1073+/-945 x 10(6)/l at month 3 (P < 0.05) and to 1133+/-728 x 10(6)/l at month 6 (P = 0.01). CD4+ cell count increased in 10 patients after 3 months and in 11 patients treated for 6 months. One child showed a continuous decrease of CD4 cells despite treatment. Before treatment the plasma HIV RNA concentration was elevated in nine children (> 4.0 log10 copies/ml) and decreased in all of them: by month 1, the mean reduction was -1.16 log10 copies/ml; by month 3, -1.38 log10 copies/ml; and by month 6, -1.53 log10 copies/ml compared with baseline. However, one child showed steadily increasing viral load from 2.7 log10 copies/ml to a maximum of 4.52 log10 copies/ml, surprisingly in association with increasing numbers of CD4 cells. This child was switched to a new combination regimen after 6 months of treatment. Plasma HIV RNA levels below limit of detection were reached in six patients: after 1 month of treatment in one patient, after 3 months in five patients, and after 6 months in six patients. There was a mean reduction of viral load from 4.56 log10+/-4.63 log10 copies/ml (n = 13) to 3.8 log10+/-3.9 log10 copies/ml (P < 0.05; n = 9) after 1 month, to 3.67 log10+/-3.88 log10 copies/ml (P < 0.01; n = 13) after 3 months, and to 3.64 log10+/-3.95 log10 copies/ml after 6 months of treatment (P < 0.001; n = 13).

CONCLUSIONS

This pilot study demonstrates the feasibility of zidovudine-lamivudine combination in children not previously exposed to antiretroviral drugs. This promising combination should therefore be evaluated in larger trials.

摘要

目的

研究齐多夫定与拉米夫定联合用药对既往未接受过抗逆转录病毒药物治疗的HIV感染儿童的耐受性和疗效。

方法

13名垂直感染儿童（年龄4个月至10岁）接受齐多夫定（约100mg/m²，每日3次）和拉米夫定（4mg/kg，每日2次）治疗。在治疗前以及治疗第1、3和6个月时监测CD4 T细胞计数、血浆HIV RNA浓度、全血细胞计数和血液化学指标。

结果

总体而言，治疗耐受性良好。1名儿童在存在抗中性粒细胞抗体的情况下出现轻度中性粒细胞减少。CD4细胞计数从基线时的851±621×10⁶/l增加到第3个月时的1073±945×10⁶/l（P<0.05），并在第6个月时增加到1133±728×10⁶/l（P = 0.01）。3个月后10名患者的CD4⁺细胞计数增加，6个月治疗后11名患者的CD4⁺细胞计数增加。1名儿童尽管接受了治疗，但CD4细胞仍持续减少。治疗前9名儿童的血浆HIV RNA浓度升高（>4.0 log₁₀拷贝/ml），所有这些儿童的血浆HIV RNA浓度均下降：到第1个月时，平均下降-1.16 log₁₀拷贝/ml；到第3个月时，-1.38 log₁₀拷贝/ml；到第6个月时，与基线相比下降-1.53 log₁₀拷贝/ml。然而，1名儿童的病毒载量从2.7 log₁₀拷贝/ml稳步增加至最高4.52 log₁₀拷贝/ml，令人惊讶的是其CD4细胞数量也增加。该儿童在治疗6个月后改用新的联合治疗方案。6名患者的血浆HIV RNA水平降至检测下限以下：1名患者在治疗1个月后，5名患者在治疗3个月后，6名患者在治疗6个月后。治疗1个月后病毒载量平均从4.56 log₁₀±4.63 log₁₀拷贝/ml（n = 13）降至3.8 log₁₀±3.9 log₁₀拷贝/ml（P<0.05；n = 9），治疗3个月后降至3.67 log₁₀±3.88 log₁₀拷贝/ml（P<0.01；n = 13），治疗6个月后降至3.64 log₁₀±3.95 log₁₀拷贝/ml（P<0.001；n = 13）。