Can We Lure Dormant HIV to Its Death?

After years of trying to determine how to eradicate every trace of HIV, a team of researchers led by Dr. Carl Siliciano at Johns Hopkins University School of Medicine may have found a critical key. Even for people with undetectable viral loads and those on aggressive treatment regimens, HIV maintains the ability to hide inside cells, creating what scientists call “HIV latent reservoirs.” These reservoirs — literally collections of HIV-infected CD4+ T cells that cannot be reached by antiretroviral treatment — can slowly “leak” HIV-positive cells that can attack cells that are otherwise healthy. When an HIV-positive person’s immune system is further compromised — by a lapse in treatment, for example — the floodgates on those reservoirs open, unleashing a new round of viral infection that can rapidly spread to healthy cells. What’s more, the infected cells in the reservoir have often mutated from their original form, meaning they cannot be detected by the human immune system, even as they attack healthy cells. 
 

“In order to achieve HIV-free for an infected individual, we have to eradicate dormant HIV,” explains Kai Deng, a postdoctoral fellow in Siliciano’s lab at the Howard Hughes Medical Institute at Johns Hopkins. Deng is the lead author of a paper published in January in the online edition of the journal Nature, which chronicles the groundbreaking success the Johns Hopkins–led team had not only in finding these latent HIV reservoirs but also training cells to use their own defense mechanisms to destroy the dormant virus. 
 

Using a complex genetic process known as “deep sequencing” on blood samples from HIV-positive people, the researchers were able to train existing T cells to become “killer T cells,” essentially attacking dormant HIV where it is hiding. Through deep sequencing, T cells can be trained to detect latently infected cells. The process of drawing out the dormant virus is still a challenge needing a more perfect solution, the researchers tell Plus, but the Johns Hopkins study provides what could be an important step toward ultimately eradicating HIV.
 

Before T cells can be trained to become “killer” and detect infected cells that are usually hidden, the person’s HIV must be well managed, the researchers caution. A key factor in achieving such management is early treatment, both Deng and Siliciano stress. “Early treatment is very important,” Deng says. “When the treatment was initiated early, the latent HIV largely remained unchanged, which is easier for killer T cells to recognize and kill. Early treatment has [also] been shown to limit the size of viral latent reservoir in infected patients, which is considered beneficial for eradication.”
 

While latent reservoirs exist in HIV-positive people regardless of what, if any, treatment they are receiving, those who obtained treatment early had the greatest levels of HIV cells existing in their original, unmutated state. The longer an HIV-positive person goes without treatment, the more opportunities the virus has to mutate, making it harder to detect and even harder for the “killer T cells” to attack. Therefore, samples from those who received treatment early — within three months of infection — saw the most success with “killer T cells” able to destroy the HIV in infected cells. 

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