一项伐昔洛韦用于抑制抗逆转录病毒治疗的 HIV/单纯疱疹病毒 2 合并感染成人减轻炎症和免疫激活的随机对照试验。

A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy.

机构信息

Department of Medicine, University of Toronto.

出版信息

Clin Infect Dis. 2013 Nov;57(9):1331-8. doi: 10.1093/cid/cit539. Epub 2013 Aug 14.

DOI:10.1093/cid/cit539

PMID:23946220

Abstract

BACKGROUND

Human immunodeficiency virus (HIV) is associated with increased systemic inflammation and immune activation that persist despite suppressive antiretroviral therapy (ART). Herpes simplex virus type 2 (HSV-2) is a common coinfection that may contribute to this inflammation.

METHODS

Sixty HIV type 1 (HIV-1)/HSV-2-coinfected adults on suppressive ART were randomized 1:1:1 to 12 weeks of placebo, low-dose valacyclovir (500 mg twice daily), or high-dose valacyclovir (1 g twice daily) in this 18-week trial. Co-primary outcome measures were the percentage of activated (CD38(+)HLA-DR(+)) CD8 T cells in blood, and highly sensitive C-reactive protein, interleukin 6, and soluble intercellular adhesion molecule 1 in plasma. Secondary outcomes included additional immune, inflammatory cytokine, and endothelial activation markers. The impact of valacyclovir (both groups combined) on each outcome was estimated using treatment × time interaction terms in generalized estimating equation regression models.

RESULTS

Participants were mostly white (75%) men who have sex with men (80%). Median age was 51 (interquartile range [IQR], 47-56) years, median duration of HIV infection was 15 (IQR, 8-21) years, median CD4 count at enrollment was 520 (IQR, 392-719) cells/µL, and median nadir CD4 count was 142 (IQR, 42-240) cells/µL. Valacyclovir was not associated with significant changes in any primary or secondary immunological outcomes in bivariate or multivariable models. Medication adherence was 97% by self-report, 96% by pill count, and 84% by urine monitoring. Eight patients had adverse events deemed possibly related to the study drug (5 placebo, 1 low-dose, 2 high-dose), and 6 patients reported at least 1 HSV outbreak (3 placebo, 3 low-dose, 0 high-dose).

CONCLUSIONS

Valacyclovir did not decrease systemic immune activation or inflammatory biomarkers in HIV-1/HSV-2-coinfected adults on suppressive ART.

CLINICAL TRIALS REGISTRATION

NCT01176409.

摘要

背景

人类免疫缺陷病毒（HIV）与全身性炎症和免疫激活有关，尽管接受了抑制性抗逆转录病毒疗法（ART），但这种炎症和免疫激活仍持续存在。单纯疱疹病毒 2 型（HSV-2）是一种常见的合并感染，可能导致这种炎症。

方法

在这项为期 18 周的试验中，60 名接受抑制性 ART 的 HIV-1/HSV-2 合并感染的成年人按 1:1:1 的比例随机分配，接受 12 周的安慰剂、低剂量伐昔洛韦（500mg，每日 2 次）或高剂量伐昔洛韦（1g，每日 2 次）。主要转归指标为血液中活化（CD38+HLA-DR+）CD8 T 细胞的百分比，以及血浆中高敏 C 反应蛋白、白细胞介素 6 和可溶性细胞间黏附分子 1。次要转归包括其他免疫、炎症细胞因子和内皮细胞激活标志物。使用广义估计方程回归模型中的治疗×时间交互项估计伐昔洛韦（两组合并）对每种结果的影响。

结果

参与者主要为白人（75%）男男性行为者（80%）。中位年龄为 51 岁（四分位距 [IQR]，47-56），中位 HIV 感染时间为 15 年（IQR，8-21），入组时 CD4 计数的中位数为 520 个/µL（IQR，392-719），CD4 计数的最低值中位数为 142 个/µL（IQR，42-240）。伐昔洛韦在双变量或多变量模型中均未与任何主要或次要免疫学结果的显著变化相关。药物依从性通过自我报告为 97%，通过药片计数为 96%，通过尿液监测为 84%。8 名患者发生了 8 起不良事件，被认为可能与研究药物有关（5 名安慰剂，1 名低剂量，2 名高剂量），6 名患者报告至少发生了 1 次单纯疱疹病毒爆发（3 名安慰剂，3 名低剂量，0 名高剂量）。