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
(Lancet 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. |
The
Pharmaceutical Journal
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