Possible new therapeutic approach for HIV
Valproic acid may offer a new approach to eliminating persistent HIV infection in resting CD4+ cells, according to researchers in the US ( 2005;366:549).
Ginger Lehrman, University of Texas Southwestern Medical Centre, Dallas, and colleagues conducted a proof-of-concept study in four HIV patients who had been taking highly active antiretroviral therapy (HAART) for at least two years. The volunteers were given subcutaneous enfuvirtide (Fuzeon) 90µg twice daily for four to six weeks to intensify HAART therapy. Oral valproic acid 500–750mg twice daily was then added to their regimen for three months.
HAART effectively suppresses plasma concentrations of HIV but it cannot eradicate latent infection in resting T cells. This latent infection persists through the agency of an enzyme called histone deacetylase 1 (HDAC1). Valproic acid is a histone deacetylation inhibitor and is able to induce HIV expression in resting T cells.
The researchers measured the frequency of latent infection before and after the addition of enfuvirtide and valproic acid, and found that it declined significantly in three out of the four patients (mean reduction 75 per cent, range 68 per cent to >84 per cent). The depletion was greater than that previously reported after intensification of HAART therapy alone. Treatment was well tolerated with only minor reactions at the enfuvirtide injection site.
“Our findings suggest that eradication of established HIV infection might be achieved in a staged approach. Patients should perhaps first be treated with standard antiretroviral regimens … for those in whom viral replication is suppressed, latent viral infection should then be tackled with HDAC inhibitors, intensified therapy, or both,” say the researchers.
Citation: Electronicjuice URI: 10020564
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