From the Journals

Second woman spontaneously clears HIV: ‘We think more are out there’


 

A fossil record of HIV

Yet, there was still HIV in the woman’s system. Dr. Laufer and Dr. Yu wanted to know whether that HIV was transmissible or whether it was a relic from when HIV was still replicating and was now defective and incapable of replicating. They performed extensive genome sequencing on nearly 1.2 billion cells that Dr. Laufer had taken from the patient’s blood in 2017, 2018, 2019, and 2020, an additional 503 million cells that were from the placenta of the baby she gave birth to in 2020, and 150 million resting CD4 T cells. Proviral sequencing was undertaken of the full DNA of the HIV to detect whether the virus was still intact. The DNA was then analyzed by use of an algorithm and was tested for mutations. The investigators tested the patient’s CD4 cells to determine whether the cells still harbored any latent HIV.

In this way, they conducted a full viral workup using tests that are far more sensitive than the viral load tests the woman had undergone in the clinic. The investigators then assessed the patient’s immune system to see what the various cells of the immune system could tell them about how well her natural immune system could identify and kill HIV. They isolated the Esperanza Patient’s immune cells and subjected those cells to HIV in the lab to see whether the cells could detect and eliminate the virus.

And just to be safe, they checked to make sure there were no antiretroviral drugs in the patient’s system.

What they found was that without treatment, her CD4 count hovered around 1,000 cells – a sign of a functioning immune system. DNA sequences revealed large chunks of missing DNA, and one sequence had an immune-induced hypermutation. In total, seven proviruses were found, but none were capable of replicating. The CD4 cells they evaluated showed no evidence of latent HIV.

In other words, they had uncovered a fossil record.

“These HIV-1 DNA products clearly indicate that this person was infected with HIV-1 in the past and that active cycles of viral replication had occurred at one point,” Dr. Yu and colleagues write in their recent article.

What may be more useful to researchers looking to turn this spontaneous cure into treatment for millions of people living with active HIV was the evidence that the woman’s immune system had trained itself to attack HIV through a number of genetic mutations. What they found, the researchers write, was evidence of “an incomplete seroconversion” – that is, when the patient was acquiring HIV, the infection was stopped in its tracks.

Yet, Dr. Yu and colleagues say that they can’t prove that the woman is fully cured of HIV.

“Although this might sound unsatisfying, it reflects an intrinsic limitation of scientific research,” they write. “Scientific concepts can never be proved through empirical data collection; they can only be disproved.”

There are more out there

Are these women the only ones to have spontaneously cleared HIV? That’s the question, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Just like they can’t disprove that the women cured themselves, they can’t prove that she and Ms. Willenberg are the only two people to have experienced this cure.

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