Ok, this is still in its infancy, but this could be the single largest breakthrough in HIV treatment since we started using cocktails -- maybe larger. I quote from the Lancet on a new article coming out this week -- the following is the abstract, and is acceptable for reproduction. ----
The Lancet 2005; 366:549-555
DOI:10.1016/S0140-6736(05)67098-5
Depletion of latent HIV-1 infection in vivo: a proof-of-concept study
Ginger Lehrman a, Ian B Hogue a, Sarah Palmer b, Cheryl Jennings c, Celsa A Spina d, Ann Wiegand b, Alan L Landay c, Robert W Coombs e, Douglas D Richman d, John W Mellors f, John M Coffin b, Ronald J Bosch g and David M Margolis email address a h
Persistent infection in resting CD4+ T cells prevents eradication of HIV-1. Since the chromatin remodeling enzyme histone deacetylase 1 (HDAC1) maintains latency of integrated HIV, we tested the ability of the HDAC inhibitor valproic acid to deplete persistent, latent infection in resting CD4+ T cells.
Procedures
We did a proof-of-concept study in four volunteers infected with HIV and on highly-active antiretroviral therapy (HAART). After intensifying the effect of HAART with subcutaneous enfuvirtide 90 μg twice daily for 4–6 weeks to prevent the spread of HIV, we added oral valproic acid 500–750 mg twice daily to their treatment regimen for 3 months. We quantified latent infection of resting CD4+ T cells before and after augmented treatment by limiting-dilution culture of resting CD4+ T cells after ex-vivo activation.
Findings
The frequency of resting cell infection was stable before addition of enfuvirtide and valproic acid, but declined thereafter. This decline was significant in three of four patients (mean reduction 75%, range 68% to >84%). Patients had slight reactions to enfuvirtide at the injection site, but otherwise tolerated treatment well.
Interpretation
Combination therapy with an HDAC inhibitor and intensified HAART safely accelerates clearance of HIV from resting CD4+ T cells in vivo, suggesting a new and practical approach to eliminate HIV infection in this persistent reservoir. This finding, though not definitive, suggests that new approaches will allow the cure of HIV in the future.
Affiliations
a University of Texas Southwestern Medical Center at Dallas, Department of Medicine, Division of Infectious Diseases, 5323 Harry Hines Boulevard, Dallas, TX 753901, USA
b HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MA, USA
c Department of Immunology/Microbiology, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL, USA
d University of California San Diego and Veterans Affairs Medical Center, San Diego, CA, USA
e Departments of Laboratory Medicine and Medicine, University of Washington, Seattle, WA, USA
f University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
g Harvard School of Public Health, Boston, MA, USA
h North Texas Veterans Health Care Systems, Dallas, TX, USA
Corresponding Author InformationCorrespondence to: Prof David Margolis
The Lancet (requries registration)