A new study finds that the barrier to discovering a cure for HIV may be higher than previously thought.
Antiretroviral drug therapy, the standard response to HIV, targets actively replicating HIV virus but has no impact on inactive, also known as latent, forms of the virus. That latent cell base, or reservoir, in HIV-infected patients consists of proviruses—viral DNA that gets inserted into the genome of the patients’ immune cells.
A newer treatment known as “shock and kill” activates the immune cells and the proviruses they harbor, and then uses 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 percent of proviruses are turned on.
In the new study, the researchers found that the proviruses are capable of replicating normally. Researchers had earlier thought these cells were defective. The Johns Hopkins researchers say that finding may indicate that the size of the latent reservoir is higher, 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,” says Robert Siliciano, the senior scientist on the study and a professor of medicine at Johns Hopkins.
“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,” Siciliano said.
The study was published ahead of an upcoming translational medicine conference “What Will it Take to Achieve an AIDS-free World?” set for November 3-5 in San Francisco. The conference was organized by the journals Cell and The Lancet, to highlight important limitations of current HIV treatment strategies. The organizers hope the conference can help lead to the development of more effective interventions.
“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.
Siciliano’s study was published in Cell.