Sagot-Lerolle Nathalie, Lamine Aurelia, Chaix Marie-Laure, Boufassa Faroudy, Aboulker Jean-Paul, Costagliola Dominique, Goujard Cécile, Pallier Coralie, Delfraissy Jean-François, Lambotte Olivier
INSERM, U802, Bicêtre, France.
AIDS. 2008 Jun 19;22(10):1125-9. doi: 10.1097/QAD.0b013e3282fd6ddc.
To investigate the impact of prolonged valproic acid treatment on the HIV reservoir in patients on highly active antiretroviral therapy.
In a single-center pilot study, the size of the HIV reservoir of 11 patients receiving valproic acid for seizures for more than 2 years was compared with 13 matched patients. In addition, the outcome of patients receiving valproic acid in the French clinical trials of scheduled treatment interruption was recorded.
Total and integrated HIV-1 DNA in, respectively, peripheral blood mononuclear cells and CD4 T cells of the patients were quantified by real-time PCR methods. The frequency of CD4 T cells carrying replication-competent virus was estimated by a quantitative limiting-dilution assay in which virus growth was detected by RT-PCR in culture supernatants of activated CD4 T cells. Clinical charts of the patients included in scheduled treatment interruption trials receiving valproic acid were reviewed.
Total and integrated HIV DNA were logarithmically more abundant than cells carrying replication-competent virus, but there was no significant difference in these three parameters between the two groups of matched patients. Three patients receiving valproic acid were included in scheduled treatment interruption trials. The rebound of viral replication was similar to that of the other patients of the trials.
Long-term valproic acid therapy seems to be insufficient to reduce the size of the HIV-1 reservoir.
探讨长期丙戊酸治疗对接受高效抗逆转录病毒治疗患者体内HIV储存库的影响。
在一项单中心试点研究中，将11例因癫痫接受丙戊酸治疗超过2年的患者的HIV储存库大小与13例匹配患者进行比较。此外，记录了法国定期治疗中断临床试验中接受丙戊酸治疗患者的结果。
通过实时PCR方法分别对患者外周血单核细胞和CD4 T细胞中的总HIV-1 DNA和整合HIV-1 DNA进行定量。通过定量极限稀释试验估计携带具有复制能力病毒的CD4 T细胞的频率，在该试验中，通过RT-PCR在活化的CD4 T细胞培养上清液中检测病毒生长。对接受丙戊酸治疗的定期治疗中断试验中患者的临床图表进行了回顾。
总HIV DNA和整合HIV DNA在对数上比携带具有复制能力病毒的细胞丰富，但两组匹配患者在这三个参数上没有显著差异。3例接受丙戊酸治疗的患者被纳入定期治疗中断试验。病毒复制的反弹与试验中的其他患者相似。
长期丙戊酸治疗似乎不足以减小HIV-1储存库的大小。
