Why an HIV Cure is so Damn Hard to Find

Last month, about a hundred people attended an HIV Cure Conference in San Diego, where Jerry Zach, MD, of the David Geffen School of Medicine at UCLA spoke about activating and eliminating HIV reservoirs. The conference was co-hosted by the National Institutes of Health’s Collaboratory of AIDS Researchers for Eradication (CARE) and University of California San Diego AntiViral Research Center where other researchers are working on different aspects of the cure.

As Zach reported, scientists have learned from a handful of temporarily cured individuals (like the “Mississippi baby”) that HIV can hide out of sight, and be undetectable in the bloodstream and yet rebound later. Reservoirs of HIV are a major barrier to any cure because the current medications can’t find and treat the virus in those reservoirs.

Although researchers don’t yet understand how, Zach explained, HIV seems capable of “going to sleep” in these reservoirs, and because it’s not reproducing, doctors can no longer detect or treat the disease.

In order to eliminate the virus, doctors need to find ways to activate those reservoirs and make them visible for treatment. Zach’s team first needed to create “latency reversing agents” to give patients with HIV who are being treated with antiretroviral therapy.

But whatever drug they do use to wake up the virus has to “be a very safe medication,” Zach said. “Because patients are perfectly fine while [HIV is] asleep.”

The additional treatment shouldn’t make undetectable patients sick while it “turns on” the sleeping virus. Once the virus can “be seen,” Zach said the next step is to develop treatments to clear those infected cells and remove the sources of HIV from the body. He said that should lead to “eradication of the infection.”

Real life examples like the Mississippi baby suggest that even low levels of the virus can later rebound and restart the infection all over again. The Mississippi baby was born HIV-positive but began antiretroviral treatment at birth before later being off the medications and appearing cured. But then the virus came back. 

Any HIV cure, Zach explained, needs to offer “some extra protection” in case any of the virus remains hidden and later rebounds.

As a recent report reveals, using molecules called “bryologs,” Zach and other researchers have demonstrated that they can now wake up HIV in the lab and make detectable “at least for short time.” But they still don’t know if they can clear the newly detectable virus or if they have “reached every cell that is infected.”

In other words, some of virus could still remain hidden. One of the other CARE researchers, Dr. Warner Greene, has shown that much of the HIV virus hides in lymphatic tissues like those found in the spleen and tonsils. (Read more about Greene’s discoveries here.)  And Dr. David Margolis, who also spoke at the conference suggested the virus could even linger in a patient’s brain cells.

Zach's team is currently conducting studies in animal models, but even if they can prove that the process works in human trials, it would just be a first step in eliminating HIV reservoirs.

“The second step,” Zach said is, “using the knowledge we’ve built over 20 years" to "alter or amend the immune system in such a way that it can see these tiny little amount of viruses we are trying to reawaken.”

Doctors would then be able to wake up the HIV and make the virus visible to antiretroviral medications or a patient’s own natural immune response. Although researchers like Zach are making progress, Margolis later reiterated that completing the collaboratory efforts to develop a multipronged HIV cure, “ain’t gonna happen fast.”