New therapeutic approach that could help eliminate dormant HIV infection

Aug 11 2005

US scientists have tested a new therapeutic approach that could help eliminate dormant HIV infection that current treatments miss. The researchers report these preliminary findings in a proof-of-concept study in this week’s issue of The Lancet.

Highly-active antiretroviral therapy (HAART) has improved the outcome for patients with HIV by targeting virus replication and restoring immune function. However, HIV can still persist in a non-replicating state in some infected cells, preventing virus eradication. Scientists know that an enzyme called histone deacetylase 1 (HDAC1) helps HIV to persist in a latent phase of infection. David Margolis (University of North Carolina at Chapel Hill, USA) and colleagues tested the ability of valproic acid, an inhibitor of HDAC, to deplete HIV infection.

The investigators enrolled four HIV-infected volunteers taking HAART with long-term suppression of the virus. They intensified the effect of HAART to prevent the spread of HIV by giving patients a drug called enfurvitide twice daily for 4–6 weeks. They then gave the patients oral valproic acid twice daily for 3 months. The researchers found that there was a 75% reduction in latent HIV infection in three out of the four patients.

Dr Margolis states: “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 at an early stage of infection . . . For those in whom viral replication is suppressed, latent viral infection could then be tackled with HDAC inhibitors, intensified therapy, or both . . . This finding, though not definitive, suggests that new approaches will allow the cure of HIV in the future.”

In an accompanying Comment Jean-Pierre Routy (McGill University Health Centre, Montreal, Canada) states: “These results, although preliminary, merit further urgent study.

In particular, they argue for a formal randomised trial to assess changes in the blood and tissue of the number of latently infected cells . . . This is the first glimpse of a new therapeutic approach that might represent a possible step towards making HIV-infection no longer a chronic disease.”