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.
"A first study reported a decrease in the frequency of circulating resting CD4þ T cells carrying replication competent HIV-1 in four patients receiving cART after 16 weeks of additional treatment with VPA (Lehrman et al., 2005). However, subsequent randomized clinical studies could not confirm these results and no significant effects of VPA were evidenced (Archin et al., 2010; Routy et al., 2012; Sagot-Lerolle et al., 2008; Steel et al., 2006). Failure of VPA was eventually associated to a poor capacity of this molecule to inhibit HDAC3, the HDAC isoform that is thought to play a preponderant role in HIV latency (Huber et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: Thirty years after the identification of HIV, a cure for HIV infection is still to be achieved. Advances of combined antiretroviral therapy (cART) in recent years have transformed HIV infection into a chronic disease when treatment is available. However, in spite of the favorable outcomes provided by the newer therapies, cART is not curative and patients are at risk of developing HIV-associated disorders. Moreover, universal access to antiretroviral treatment is restricted by financial obstacles. This review discusses the most recent strategies that have been developed in the search for an HIV cure and to improve life quality of people living with HIV.
"HAART could then stop the virus, whilst the immune system could destroy the infected cells. These findings have however been challenged . The above mentioned function of VPA as an HDAC inhibitor has also led to its use in direct reprogramming in generation of induced pluripotent stem (iPS) cells, where it has been shown that addition of VPA allows for reprogramming of human fibroblasts or neural stem cells to iPS cells without addition of genetic factors . "
[Show abstract][Hide abstract] ABSTRACT: Valproic acid (VPA) is an anti-epileptic and mood-stabilizing compound successfully used in the clinics since many decades. During the last few years, research on VPA revitalized. VPA has profound impact on nuclear chromatin structure in target cells by impinging on epigenetic mechanisms such as inhibition of histone deacetylase HDAC1, with implications for HIV and cancer treatment, and for the direct reprogramming in generation of induced pluripotent stem (iPS) cells. VPA can thus act at multiple levels and in several cellular systems. In addition to its established applications for the treatment of neurological and psychiatric disorders, and its newly discovered epigenetic mechanisms of action, the peripheral metabolic effects of VPA administration, in particular impinging on the heart and on the liver, are now starting to be understood. These have important consequences for the management of therapy and also for investigation purposes. The aim of this article is on one hand to summarize the emerging knowledge on the role of VPA during the occurrence of cardio-metabolic dysfunctions and on the other hand to describe concisely the VPA-induced epigenetic modifications in target cells.
"It is also used to treat migraine headache and schizophrenia . Recently, VPA is under investigation for treatment of HIV and various cancers . VPA not only suppresses tumour growth and metastasis, but also induces tumour differentiation in vitro and in vivo. "
[Show abstract][Hide abstract] ABSTRACT: SEC is an undifferentiated tumour used in tumour studies. MTX is an antimetabolite used in treatment of cancer, autoimmune diseases and induction of abortion. VPA is used as anticonvulsant and is under investigation for treatment of cancer. The aim of this work was to compare between the effect of each of MTX and VPA on solid Ehrlich tumour in mice.
Forty albino mice were divided into 4 equal groups: control untreated group, SEC group, SEC+MTX group, and SEC+VPA group. Tumour volume, tissue CAT, tissue GR, tissue MDA, tissue cholesterol and tissue TNF-α were determined. A part of the tumour was examined for histopathological and immunohistochemical study.
MTX alone or VPA alone induced a significant increase in tissue CAT and GR with a significant decrease in the tumour volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with a significant increase in p53 expression compared to SEC group. This effect was more significant in MTX treated group compared to VPA treated group.
MTX has more antitumour effect than VPA against SEC.
Journal of the Egyptian National Cancer Institute 12/2012; 24(4):161-7. DOI:10.1016/j.jnci.2012.08.001
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.