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更昔洛韦 CMV 治疗对精液和血液中免疫激活和 HIV 病毒载量的影响:一项观察性临床研究。

Impact of CMV therapy with valganciclovir on immune activation and the HIV viral load in semen and blood: an observational clinical study.

机构信息

*Clinical Sciences Division, University of Toronto, Toronto, Ontario, Canada; †Deptartment of Pathology and Molecular Medicine, Queens University Kingston, Ontario, Canada; ‡Maple Leaf Medical Clinic, Toronto, Canada; §University Health Network, Toronto, Canada; and ¶Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

出版信息

J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):251-8. doi: 10.1097/01.qai.0000435256.34306.c1.

DOI:10.1097/01.qai.0000435256.34306.c1
PMID:24091693
Abstract

BACKGROUND

The HIV RNA viral load (VL) in vaginal secretions and semen is an independent predictor of HIV transmission. Blood VL is associated with semen VL, and local mucosal factors, such as semen cytomegalovirus (CMV) reactivation, may play an important role.

METHODS

Twenty-one HIV-CMV-coinfected, antiretroviral-naive men received 900 mg of oral valganciclovir once daily for 2 weeks in an open-label study. Blood and semen were collected at baseline, after 2 weeks of valganciclovir, and 2 months after therapy completion. The primary end point was change in semen HIV levels at 2 weeks, and the secondary end points were change in semen HIV VL at 2 months and change in semen CMV levels.

RESULTS

The HIV VLs fell significantly at 2 weeks in semen (median 3.44-3.02 log10 copies/mL, P = 0.02) and blood (median 3.61-3.10 log10 copies/mL, P < 0.01) and returned to baseline after therapy completion (median 3.24 and 3.71 log10 copies/mL in semen and blood, respectively). Semen CMV levels also fell on treatment (median 2.13-1.62 log10 copies/mL, P < 0.01) and continued to fall after therapy completion (median 0.91 log10 copies/mL at week 8, P < 0.001 vs. baseline). The reduced semen CMV VL was associated with decreased semen T-cell activation and enhanced CMV-specific T-cell responses in blood; changes in the semen HIV VL were not associated with immune parameters.

CONCLUSIONS

Although valganciclovir therapy was associated with reduced HIV and semen CMV levels, these results suggest that the reduced HIV VL was a direct drug effect rather than a CMV antiviral effect or CMV-associated immune alterations.

摘要

背景

阴道分泌物和精液中的 HIV RNA 病毒载量(VL)是 HIV 传播的独立预测因素。血液 VL 与精液 VL 相关,局部黏膜因素,如精液巨细胞病毒(CMV)再激活,可能发挥重要作用。

方法

21 例 HIV-CMV 合并感染、未接受抗逆转录病毒治疗的男性接受了为期 2 周的口服缬更昔洛韦 900mg 每日 1 次的开放标签研究。在基线、缬更昔洛韦治疗 2 周后和治疗完成后 2 个月采集血液和精液。主要终点是 2 周时精液中 HIV 水平的变化,次要终点是 2 个月时精液 HIV VL 的变化和精液 CMV 水平的变化。

结果

精液中的 HIV VL 在 2 周时明显下降(中位数 3.44-3.02 log10 拷贝/ml,P=0.02)和血液(中位数 3.61-3.10 log10 拷贝/ml,P<0.01),并在治疗完成后恢复到基线(精液和血液中的中位数分别为 3.24 和 3.71 log10 拷贝/ml)。精液 CMV 水平也在治疗期间下降(中位数 2.13-1.62 log10 拷贝/ml,P<0.01),并在治疗完成后继续下降(第 8 周时中位数 0.91 log10 拷贝/ml,P<0.001 与基线相比)。降低的精液 CMV VL 与降低的精液 T 细胞激活和增强的血液 CMV 特异性 T 细胞反应相关;精液 HIV VL 的变化与免疫参数无关。

结论

尽管缬更昔洛韦治疗与降低 HIV 和精液 CMV 水平相关,但这些结果表明,降低的 HIV VL 是直接的药物作用,而不是 CMV 抗病毒作用或 CMV 相关免疫改变的结果。

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