AIDS. 1998 Oct 1;12(14):F151-60.
To evaluate the toxicity, tolerability and effect on laboratory markers of adding lamivudine (3TC) to nucleoside analogue reverse transcriptase inhibitors (NRTI) in children with HIV-1 infection.
Randomized double-blind trial.
HIV-1-infected children on stable NRTI therapy were randomized to receive 3TC syrup or tablets (4 mg/kg twice daily) or matching placebo in addition to existing therapy. Endpoints were serious adverse events, and changes in CD4 cell count and plasma HIV-1 RNA. Analyses were on an intention-to-treat basis.
A total of 162 (81 on 3TC, 81 on placebo) children [median age, 6.5 years; interquartile range (IQR), 4.1-10.1 years] were included. At randomization, 52 were receiving zidovudine (ZDV), 39 didanosine (ddl), 54 ZDV-ddl and 17 ZDV-zalcitabine (ddC); 32 (20%) had AIDS; median CD4 cell count was 328 x 10(6)/I (IQR, 127-696 x 10(6)/l), and median HIV-1 RNA was 4.9 log10 copies/ml (IQR, 4.3-5.4 log10 copies/ml). Median follow-up was 40 weeks (IQR, 29-49 weeks) and 76% of follow-up was on blinded therapy for both 3TC and placebo groups. There were 11 serious adverse events in the blinded phase [two clinical (both placebo) and nine laboratory (five 3TC, four placebo)], five (two 3TC, three placebo) resulting in stopping trial drug. At 24 weeks, the CD4 cell count was greater in the 3TC group by a median of 47 x 10(6)/l and HIV-1 RNA was lower by 0.30 log10 copies/ml (P = 0.03 and 0.002, respectively, versus the placebo group). The difference in reduction in HIV-1 RNA up to 24 weeks, as measured by area under the curve minus baseline, between 3TC and placebo groups was 0.38 log10 copies/ml (95% confidence interval, 0.12-0.65) greater in children taking ZDV-containing regimens at baseline, compared with those on ddl monotherapy (P = 0.005), after adjusting for other factors at baseline. Thirteen children developed new AIDS events (six on 3TC, four on placebo) of whom three died (all placebo).
The addition of 3TC to current NRTI therapy in children was safe and well-tolerated. There was evidence that treatment changes in HIV-1 RNA viral load were greater in children taking regimens that included ZDV.
评估在感染人类免疫缺陷病毒1型（HIV-1）的儿童中，在核苷类似物逆转录酶抑制剂（NRTI）基础上加用拉米夫定（3TC）的毒性、耐受性及对实验室指标的影响。
随机双盲试验。
接受稳定NRTI治疗的HIV-1感染儿童被随机分组，在现有治疗基础上，分别接受3TC糖浆或片剂（4毫克/千克，每日两次）或匹配的安慰剂。观察终点为严重不良事件、CD4细胞计数及血浆HIV-1 RNA的变化。分析采用意向性治疗原则。
共纳入162名儿童（3TC组81名，安慰剂组81名）[中位年龄6.5岁；四分位间距（IQR），4.1 - 10.1岁]。随机分组时，52名接受齐多夫定（ZDV）治疗，39名接受去羟肌苷（ddI）治疗，54名接受ZDV-ddI治疗，17名接受ZDV-扎西他滨（ddC）治疗；32名（20%）患有艾滋病；中位CD4细胞计数为328×10⁶/升（IQR，127 - 696×10⁶/升），中位HIV-1 RNA为4.9 log₁₀拷贝/毫升（IQR，4.3 - 5.4 log₁₀拷贝/毫升）。中位随访时间为40周（IQR，29 - 49周），3TC组和安慰剂组76%的随访期采用盲法治疗。盲法治疗阶段有11起严重不良事件[2起临床事件（均为安慰剂组）和9起实验室事件（3TC组5起，安慰剂组4起）]，5起（3TC组2起，安慰剂组3起）导致停用试验药物。在24周时，3TC组CD4细胞计数中位数比安慰剂组高47×10⁶/升，HIV-1 RNA比安慰剂组低0.30 log₁₀拷贝/毫升（与安慰剂组相比，P值分别为0.03和0.002）。在基线时接受含ZDV方案治疗的儿童中，3TC组与安慰剂组相比，至24周时HIV-1 RNA曲线下面积减去基线值所测得的HIV-1 RNA降低差异为0.38 log₁₀拷贝/毫升（95%置信区间，0.12 - 0.65），在调整基线时的其他因素后，与接受ddI单药治疗的儿童相比差异有统计学意义（P = 0.005）。13名儿童出现新的艾滋病相关事件（3TC组6名，安慰剂组4名），其中3名死亡（均为安慰剂组）。
在儿童当前的NRTI治疗中加用3TC是安全且耐受性良好的。有证据表明，接受含ZDV方案治疗的儿童，其HIV-1 RNA病毒载量的治疗变化更大。
