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 Press October 24th in the journal Cell has shown that it could be 60 times larger than previously thought. The findings, publishing ahead of the upcoming translational medicine conference "What Will it Take to Achieve an AIDS-free World?" organized by Cell and The Lancet, highlight important limitations of current treatment strategies and could lead to the development of more effective interventions.

"We would like to use these findings by developing better ways to measure the size of the latent reservoir in patients who are participating in future trials of potentially curative strategies," says senior study author Robert Siliciano of Johns Hopkins University School of Medicine. "In this way, we think our analysis will contribute to HIV eradication efforts."

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.

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, and it is unclear how long it will take to find a way to do this."

In an effort to bridge the gap between clinicians and researchers focused on understanding, preventing, and curing HIV/AIDS, Siliciano is co-organizing a conference with Kenneth Mayer (the Fenway Institute) and Editors from Cell and The Lancet called "What Will it Take to Achieve an AIDS-free World?" Taking place November 3rd through 5th in San Francisco, California, the meeting will bring scientists and clinicians together in editorially curated sessions designed to catalyze the development of new translational approaches and solutions. "We would like to bring together basic virologists and immunologists, experts in vaccine development and drug treatment, and public health experts to discuss the most important approaches to ending the epidemic," Siliciano says.

Cell, Ho et al.: "Replication-competent non-induced proviruses in the latent reservoir increase barrier to HIV-1 cure."

For more information on the upcoming Translational Medicine Conference "What Will It Take to Achieve an AIDS-free World?", please visit http://www.translationalmedicine-lancet-cell.com/HIV/index.html

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