Drug brings HIV out of hiding
A study has boosted the prospects of a cure for HIV. For the first time, results have shown that a drug can safely kick-start production of the dormant virus in patients, so that it might be detected and attacked more easily by the immune system.
The finding was announced today at the 19th annual Conference on Retroviruses and Opportunistic Infections in Seattle, Washington. But other studies released at the same event suggest that merely flushing the virus out of hiding is not enough to kill infected cells and that a cure is some way off.
HIV integrates itself into cell genomes, causing the cells to make new copies of the virus when they transcribe their own DNA. But in some cells, HIV survives for decades in a resting, or latent, state without transcribing its genes to make new viruses. This renders the infected cells in the 'latent reservoir' invisible to the bodys immune defences and to antiretroviral treatment.
Suberoylanilide hydroxamic acid seems to force HIV to make copies of itself, potentially making infected cells more visible to the body's immune system.
NIBSC/SPL
Studies had suggested that a drug called suberoylanilide hydroxamic acid (SAHA) could push the virus out of its slumber, but the approach had not been tested in people. So researchers led by David Margolis, a molecular virologist at the University of North Carolina at Chapel Hill, treated six people with a single dose of SAHA and tested its effect on CD4+ T cells immune cells that are targeted for infection by HIV. The study found that SAHA did kick-start transcription of HIV in latently infected CD4+ T cells: researchers detected nearly 5 times as many HIV transcripts in the patients resting CD4+ T cells after treatment as before. There were no serious side effects.
This study provides the first proof-of-concept demonstration of disruption of latency, which is a significant step towards eradication of HIV from the body, says Margolis.
But Margolis and other researchers are cautious about what the study means in the quest for an HIV cure. Sharon Lewin, an infectious-disease doctor at Monash University in Melbourne, Australia, is also studying SAHA in patients; so far, 10 have taken the drug for two weeks without experiencing serious side effects. But, she says, no study has yet demonstrated that activating latent HIV leads to destruction of infected cells.
Margolis's study, says Lewin, looked at a small number of patients, and although it is an important step to show that the drug has caused some alteration in viral production, we dont yet know how that translates into getting rid of latent infected cells.
At the Seattle conference, Liang Shan, a researcher at Johns Hopkins University in Baltimore, Maryland, presented the results of a study, published today in Immunity1, in which CD4+ T cells were taken from people with HIV and treated with SAHA in vitro. The cells did not die, even when combined with the patients' own 'killer' T cells, which are specialized to destroy virus-infected cells. However, when the killer T cells were first exposed to pieces of HIV, they did destroy the infected cells.
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Drug brings HIV out of hiding