Barrier to HIV cure bigger than previously thought

The journal Cell just published Bob Siliciano and pals data on the enormity of HIV’s latent reservoirs. According to the research, the new estimate of resting – but replication competent – T-cell reservoirs seriously diminish the possibility that most of those with HIV can be easily cured. However, the data bolsters the case for frequent HIV screening. The chance of being functionally cured (the immune system can control HIV on its own without needing meds) or actually cured (HIV is eliminated from the body) can be significantly enhanced by early detection and treatment of HIV infection. Those who begin early treatment – starting within months of infection –  can prevent the build up of these infected cell reservoirs. This seems to be key for at least becoming functionally cured (example: the VISCONTI study).

A press release excerpt on Siliciano’s HIV reservoirs study is below as are some video of him on the topic.

The Journal Cell: Barrier to HIV cure bigger than previously thought

HIV infection is typically treated with antiretroviral therapy, which targets actively replicating HIV but does not affect inactive or latent forms of the virus. The latent reservoir is the biggest barrier to curing HIV, and a study published by Cell October 24th in has shown that it could be 60 times larger than previously thought. The findings were published ahead of the upcoming translational medicine conference “What Will it Take to Achieve an AIDS-free World?”.

The latent reservoir in HIV-infected patients consists of proviruses—viral DNA that gets inserted into the genome of the patients’ immune cells. A treatment strategy known as “shock and kill” involves activating these immune cells and the proviruses they harbor, and then using antiretroviral therapy to keep the activated viruses from infecting other cells. But when these immune cells are activated in the test tube, less than 1% of proviruses are turned on, according to recent estimates using standard methods that measure the size of the latent reservoir.

HIV infection is typically treated with antiretroviral therapy, which targets actively replicating HIV but does not affect inactive or latent forms of the virus. The latent reservoir is the biggest barrier to curing HIV. 

In the new study, Siliciano and his team set out to characterize the vast majority of proviruses that are not affected by this intervention. They found that a significant proportion of these noninduced proviruses have intact genomes and are capable of replicating normally, in contrast to the prevailing belief that they are defective. Moreover, these intact noninduced proviruses may increase the size of the latent reservoir by a factor of 60, compared with previous estimates. “These results indicate an increased barrier to cure, as all intact noninduced proviruses need to be eradicated,” Siliciano says. “Although cure of HIV infection may be achievable in special situations, the elimination of the latent reservoir is a major problem.”

Videos : Siliciano explains the newly published data here.  Below, at the IAS conference earlier this year, Siliciano explained the challenges of eliminating HIV latent cell reservoirs.

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