"Elite Controllers" Give Hope for an HIV Cure

Virus HIV

Researchers have published a study of a woman being called the "Esperanza patient," one of what researchers call "elite controllers," who seem to eradicate HIV naturally. 

There are two known cases of people having been "cured" of HIV: Timothy Ray Brown, dubbed the "Berlin Patient," and Adam Castillejo, dubbed the "London Patient." Both underwent complicated stem cell transplants after acquiring leukemia (Brown) or Hodgkin's lymphoma (Castillejo). 

The 30-year-old woman, who was diagnosed with HIV in 2013, lives in Esperanza, Argentina. Her immune system appears to have cured her of HIV.

"I enjoy being healthy," she told NBC News. "I have a healthy family. I don't have to medicate, and I live as though nothing has happened. This already is a privilege."

Although via cocktails of antivirals, HIV can be controlled, the virus remains hidden in T-cells in the body, in what are called "viral reservoirs." The drugs keep the viral DNA, called a provirus, under control, but the disease will recur if the person stops taking the drugs.

The Esperanza patient's immune system is someone how able to suppress the HIV virus's replication with drugs. The occurrence of such people is about 1 in 200.

"This is really the miracle of the human immune system that did it," said Xu Yu, a viral immunologist at the Ragon Institute in Boston, who partnered with Natalia Laufer, a physician scientist at INBIRS Institute in Buenos Aries, Argentina.

The researchers performed exhaustive analysis on 64 people who, like the Esperanza patient, are elite controllers. They found that these people's immune systems have destroyed cells that harbor HIV. The cells that were left over were infected cells where the viruses' genome was spliced into regions of cellular DNA too far from the machinery that stimulates viral replication.

One of the people analyzed was Loreen Willenberg, who is a now-67-year-old woman from California. She was diagnosed with HIV in 1992. Researchers have sequenced billions of her cells but have found no intact viral sequences, making her case similar to the Esperanza patient.

The research team analyzed 1.2 billion of the Esperanza patient's blood cells in search of viable HIV. A mother, they also evaluated 500 million placental-tissue cells after she gave birth to a baby in March 2020 who was HIV-negative. Of the 1.118 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues analyzed, seven defective proviruses, some derived from clonally expanded cells, were detected. But a viral outgrowth assay test did not retrieve replication-competent HIV from 150 million resting CD4+ T cells, and no HIV-1 RNA was detected in 4.5 mL of plasma.

"The study sets the standard for demonstrating that the Esperanza patient has no replication-competent proviral DNA within her cells," said Carl Dieffenbach, director of the Division of AIDS at the National Institute of Allergy & Infectious Diseases (NIAID), part of the National Institutes of Health. The study was funded by NIAID and the Bill & Melinda Gates Foundation. "The more of these patients we uncover and work up, the more complete our understanding of what a cured patient looks like."

Aside from being a scientific curiosity, researchers hope that what they learn from the Esperanza patient and elite controllers like her can be applied to general HIV populations. Perhaps the mechanisms of action seen with these individuals' immune systems can lead to new immunotherapies or retroviral drugs.

"This gives us hope that the human immune system is powerful enough to control HIV and eliminate all the functional virus," Xu Yu said. "Time will tell, but we believe she has reached a sterilizing cure."

Steven Deeks, an HIV researcher and professor of medicine at the University of California, San Francisco, who was not involved in the study, who has worked with Xu Yu in the past, said that he wants to learn more about what happens in patients such as the Esperanza patient the first couple days and weeks after becoming infected. They don't know why her immune system didn't develop antibodies to the HIV proteins they would have expected her to, suggesting that her immune system somehow prevents viral replication early before the virus can spread and become too much for her immune system to control. That typically only happens when people begin antiretroviral drugs very early.

The study was published in Annals of Internal Medicine.

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