Issue: October 2020
Disclosures: Yu reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
August 27, 2020
3 min read
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Was a patient cured of HIV without a stem cell transplant?

Issue: October 2020
Disclosures: Yu reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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In a study explaining how certain patients can control HIV without medication, researchers reported what one of them called “a provocative idea.”

In one of the so-called elite controllers, the researchers were unable to detect any HIV in more than a billion cells, raising the possibility that the patient has achieved a sterilizing cure.

Xu Yu pullquote

To date, only two people are believed to have been cured of HIV, most recently the so-called “London patient.” Both achieved sustained remission after undergoing stem cell transplantation, a risky treatment that is not suitable for most patients.

Healio spoke with Xu G. Yu, MD, group leader at the Ragon Institute of MGH, MIT and Harvard and associate professor of Medicine at Harvard Medical School, about the possibly cured patient, the study’s other findings and their implications for HIV patient care.

Q: What are this study’s key takeaways?

A: The quality, rather than quantity, of the HIV reservoirs define a state of a functional cure of HIV. We found that in elite controllers, HIV was often found in locations of the human genome that researchers call “gene deserts.” In these inactive parts of the human genome, human DNA is never turned on, and thus, HIV cannot be effectively expressed but remains in a “blocked and locked” state. This means that viral genomes at these positions are blocked from being expressed and therefore are incapable of causing disease.

Our data indicate that for future evaluation of cure strategies, not only the changes in the quantity of intact viruses, but also the changes in the chromosomal locations and integration sites of intact viruses should be analyzed as an outcome parameter or endpoint.

It may be possible to achieve a sterilizing cure of HIV through natural immunity. Notably, a sterilizing cure of HIV has so far been achieved only after hematopoietic stem cell transplantation.

Q: What makes elite controllers different from virally suppressed patients?

A: HIV elite controllers can spontaneously maintain undetectable HIV viremia in the absence of any ART. They represent less than 0.5% of all HIV-infected individuals. We believe that these elite controllers were able to achieve this drug-free control of HIV through their natural immunity, unlike the general persons living with HIV who normally can achieve viral suppression only through taking daily ART.

We like to refer to elite controllers as having a “functional cure.” However, [one of the participants] seems to have a sterilizing cure.

Q: What is different about the woman whose test results suggest she has been cured?

A: In the rare instance, such as in [the participant] in our study, we failed to detect intact HIV despite analyzing more than 1.5 billion cells. We hypothesize that this patient has achieved a sterilizing cure of HIV-1 through natural immune-mediated mechanisms — a provocative idea given that a sterilizing cure of HIV has previously been observed only after a highly toxic hematopoietic stem cell transplantation.

We are currently searching for more elite controllers who also may have achieved a sterilizing cure of HIV. If so, HIV infection may in the future be regarded as a disease that can naturally heal in rare instances.

Q: Are the findings relevant to the care of other patients with HIV?

A: The strengths of the study is that it gives us a blueprint what a functional cure of HIV looks like. For inducing a cure of HIV in larger numbers of HIV-1-infected individuals, we don’t have to get rid of all intact HIV sequences in their genomes — we need to target only those viruses that are located in active parts of the human genome where they can be actively expressed. In the future, we will consider immunotherapeutic interventions that are specifically designed to eliminate those HIV sequences that are integrated in active parts of the human genome. The remaining sequences that are integrated in inactive parts of the human genome do not seem to cause disease, and it looks like they can largely be ignored.

In addition, we are also analyzing the viral reservoir profile in some long-term ART-treated individuals to see whether some of these persons would have a reservoir profile that we see in HIV elite controllers.