Fight to cure HIV gets tougher as study sheds light on hidden virus

Just as some scientists were becoming more hopeful about finding a way to overcome HIV's ability to resist, evade, and otherwise survive efforts to rid it from the body, another hurdle has emerged, new research from Johns Hopkins shows.

In a cover-story report published in the journal Cell, Johns Hopkins infectious disease experts say the amount of potentially active, dormant forms of HIV hiding in infected immune cells may actually be 60-fold greater than previously thought. The hidden HIV, researchers say, is part of the so-called latent reservoir that remains long after antiretroviral drug therapy has successfully brought viral replication to a standstill. The disappointing finding comes after a three-year series of lab experiments, which researchers say represents the most detailed and comprehensive analysis to date of the latent reservoir of HIV proviruses.

If antiretroviral therapy is stopped or interrupted, the study found, some proviruses can reactivate, allowing HIV to make copies of itself and resume infection of other immune cells. Senior study investigator Robert Siliciano, who in 1995 first showed that reservoirs of dormant HIV were present in immune cells, says that while the study shows most proviruses in the latent reservoir are defective, curing the disease will depend on finding a way to target all proviruses with the potential to restart the infection.

In the study, 213 HIV proviruses were isolated from the reservoirs of eight patients. Though the proviruses were initially unresponsive to highly potent biological stimuli, some 12 percent could later still become active and were capable of replicating their genetic material and transmitting infection to other cells. Siliciano, a professor at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator, says that all of these non-induced proviruses had previously been thought to be defective, with no possible role in resumption of the disease.

The team's findings pose a serious problem to prevailing hopes for the so-called "shock and kill" approach to curing HIV, Siliciano says. He adds that this new discovery could boost support for alternative approaches to a cure, including renewed efforts to develop a therapeutic vaccine to stimulate immune system cells that attack and kill all HIV.

"Our study results certainly show that finding a cure for HIV disease is going to be much harder than we had thought and hoped for," he says.

Currently, there are more than 34 million people in the world living with HIV, including an estimated 1,178,000 in the United States.