Reservoirs of Latent HIV Hinder Quest for a Cure


In patients who are being treated with antiretroviral therapy (ART), it appears that a latent form of HIV residing in immune cells can continue to reproduce.

HIV has remained stubbornly impervious to a complete cure, and researchers have uncovered new evidence that may explain this problem, at least in part. In patients who are being treated with antiretroviral therapy (ART), it appears that a latent form of HIV residing in immune cells can continue to reproduce, potentially reactivating the virus in the body and offering resistance against ART.

According to researchers at Johns Hopkins University School of Medicine, this latent HIV has an extremely long half-life, presenting a significant obstacle to complete eradication of the disease.

To learn more about the reservoir of latent HIV in immune cells, the research team grew CD4 cells from the blood of 12 HIV-positive patients who were on ART. The cells were then stimulated with rounds of various chemicals to induce them to divide and proliferate. Each time the cells were stimulated they were split into 2 groups, one of which was the control group. The other group of cells would then go through the stimulation process again. The researchers discovered that the stimulated cells were able to proliferate without releasing active HIV, but that the new cells created from this division actually did emit active HIV.

In addition, the scientists discovered that when they sequenced the genomes of the viruses that were released after each stimulation, the viruses were almost all genetically identical. This gave support to the theory that the viruses had replicated during the study rather than that they came from different HIV types, as some infected people harbor more than one type of HIV.

“These [latently infected] cells are present in everybody [with HIV], but they’re very rare—about 1 in a million,” Robert Siciliano, MD, PhD, professor of medicine at Johns Hopkins University School of Medicine and an author of the study, told Contagion®, adding that the medical community has known for roughly 20 years that these cells exist in HIV patients. “What’s new in the last year is understanding why these latently infected cells never go away.”

The scientists discovered that these cells divide without producing HIV, although later they may begin to produce the virus; researchers aren’t sure why this happens. “The finding that they are actually proliferating is disturbing,” Siciliano said, adding that this cell replication is the reason the scientific community has been unable to come up with a complete cure: “This division helps keep these cells from disappearing.” By contrast, he notes, hepatitis C has proven quite curable because a latent form of the disease doesn’t exist. Patients are able to take medications that eradicate the virus; once a person has gone three months without detectable levels of hepatitis C in the blood, he or she is considered cured.

Going forward, Dr. Siciliano and his team plan to focus on HIV’s propensity to replicate. “We’d like to figure out what’s causing the proliferation [of the cells] and if there’s any way to stop it,” he said. If their research yields answers, this will likely represent a real breakthrough in the quest to wipe out HIV for good.

Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.

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