Life Sci. 2011 May 23;88(21-22):909-16. doi: 10.1016/j.lfs.2011.03.022. Epub 2011 Apr 6.
This report is a summary of a symposium entitled "Mother-to-Child Transmission (MTCT) of HIV and Drugs of Abuse in Highly Active Antiretroviral Therapy (HAART) Era," organized by The National Institute on Drug Abuse, National Institutes of Health in Rockville, Maryland, October 13, 2009. In the pre-HAART era, the prevalence of MTCT of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant factor in MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. In the Unites States, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT in the HAART era is still of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load through a variety of putative mechanisms such as: a) promoting HIV mutation and replication through non-adherence to HAART; b) impairing the efficacy of HAART through drug-drug interaction; and c) promoting HIV replication in monocyte/macrophages. Drugs of abuse may promote HIV replication by increasing the expression of CCR5 receptors, decreasing the expression of CCR5 receptor ligands, increasing the expression of CXCR4 receptors, increasing the expression of DC-SIGN, and possibly inducing epigenetic changes.
本报告是 2009 年 10 月 13 日,由马里兰州罗克维尔市美国国立卫生研究院国家药物滥用研究所组织的题为“高效抗逆转录病毒治疗(HAART)时代母婴传播(MTCT)艾滋病毒和药物滥用”的研讨会的总结报告。在 HAART 前时代,HIV 母婴传播的流行率约为 25%,孕妇滥用药物(非法药物和吸烟)是母婴传播的重要因素。然而,随着 HAART 的引入,HIV 母婴传播的比例已降至 2%以下。在美国,估计目前约有 5.1%的孕妇使用非法药物,16.4%的孕妇吸烟。HAART 时代 MTCT 的残留流行率仍令人担忧,这可能与孕妇中持续存在的物质使用有关。在本报告中,我们回顾并提出了证据,支持这样一种假设,即滥用药物确实有可能增加 HAART 存在时 HIV 的母婴传播。孕妇接触滥用药物可能会通过多种机制增加 HIV 的母婴传播,包括可能对胎盘造成损害、诱导早产,以及通过多种推测机制增加母体血浆病毒载量,例如:a)通过不遵守 HAART 促进 HIV 突变和复制;b)通过药物相互作用损害 HAART 的疗效;c)促进单核细胞/巨噬细胞中的 HIV 复制。滥用药物可能通过增加 CCR5 受体的表达、减少 CCR5 受体配体的表达、增加 CXCR4 受体的表达、增加 DC-SIGN 的表达,并可能诱导表观遗传变化,从而促进 HIV 复制。