November 2021
Examples of media coverage:
- Woman’s own immune system has possibly cured her of HIV – Benjamin Ryan, NBC News, November 15, 2021
- Scientists report finding a second person to be ‘naturally’ cured of HIV, raising hopes for future treatments – Megan Molteni, STAT News, November 15, 2021
- A Second Woman May Be Naturally Cured of HIV – Liz Highleyman, POZ Magazine, November 15, 2021
- A second HIV patient may have been ‘cured’ of infection without stem cell treatment, in extremely rare case – Jacqueline Howard, CNN, November 16, 2021
- Second Woman Spontaneously Clears HIV: ‘We Think More Are Out There’ – Heather Boerner, Medscape, November 16, 2021
Original sources:
- Journal article: A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation – Annals of Internal Medicine, November 16, 2021
- Editorial: The Esperanza Patient: More Hope for a Sterilizing HIV-1 Cure – Annals of Internal Medicine, November 16, 2021
TAG’s commentary:
A new study published by Xu Yu and colleagues in the Annals of Internal Medicine has generated extremely widespread media coverage. The report presents hopeful news about a possible second case in which a person’s immune system cleared all intact HIV from their body.
In contrast to many stories covered in the past on TAG’s Cure Research Media monitor, most of the news articles are admirably accurate, including the excellent NBC news coverage by Benjamin Ryan linked to above.
The published scientific paper is a case report about a 30-year-old woman in Argentina known as the Esperanza patient, who has chosen to remain anonymous to retain privacy. The woman was diagnosed HIV-positive by antibody testing in March 2013, but viral load has been persistently undetectable by commercial viral load tests over eight years of follow up. The woman thus met the criteria to be considered an elite controller.
Antiretroviral therapy (ART) was prescribed for a six-month period from September 2019 to March 2020, when the woman became pregnant, but stopped again after the birth of her healthy HIV-negative child. Viral load stayed undetectable throughout.
The crux of the study is that the researchers searched for evidence of HIV in vast numbers of peripheral blood cells (1.188 billion) sampled via standard blood draws and a procedure called leukapheresis. An additional sample of 503 million mononuclear cells was obtained from placental tissue after delivery of her baby.
No intact HIV capable of replicating could be found. A total of seven defective HIV DNA copies were identified in peripheral blood cell samples, and none in the placenta. Of these, most were missing parts of the HIV genetic code (deletions) and only one was nearly complete but contained hypermutations known to prevent virus replication.
These hypermutations in the virus genetic code are known to result from the antiviral activity of certain human cellular proteins, and so they represent evidence that HIV was replicating in the woman’s body at some point in the past.
The researchers were able to detect the presence of both CD4 and CD8 T cell immune responses targeting HIV, in addition to antibodies against some viral proteins. The antibodies recognized fewer viral proteins than is the case in most HIV-positive people, suggesting that viral replication had been very rapidly curtailed after infection before a broader array of antibody responses could develop.
In a discussion of their findings, the researchers explain that it is impossible to definitively prove that all the HIV that was capable of replicating has been cleared. But they believe the evidence supporting this conclusion is very strong.
The Esperanza patient is the second such case of an HIV elite controller potentially clearing all viable virus. The first was Loreen Willenberg, whose case was reported in a paper in the journal Nature in 2020.
The findings offer hope that there are immune mechanisms that can be identified and exploited to develop curative therapies for HIV. There is however a caveat: it could be that there are unique traits in these rare individuals, or unusual aspects of their HIV infection which cannot be replicated or translated to others.
Some of the news coverage uses the terminology “natural cure” to refer to the apparent role of the immune system in these cases, and it’s important to appreciate that this is not referring to products that get sold online or over the counter as “natural” therapies.
The research paper itself chooses to use the term “sterilizing cure” to describe the possible elimination of all viable HIV from the body. This terminology is not favored by many researchers and community-based advocates because of its negative connotations: sterilizing means cleaning, and the term “clean” has a history of being used as stigmatizing language to refer to HIV-negative status.
There is nothing unclean about a viral infection, the human body is full of viruses and bacteria, including ancient retroviruses that are now part of the human genetic code (genome). One such ancient retrovirus, HERV-K, contributes proteins to the placenta. If it was possible to completely sterilize the human body of all viruses and bacteria, it would be fatal.
All stakeholders in HIV cure research need to work together to select less stigmatizing terminology, whether “complete cure” or another alternative.
As an addendum, the NBC News report includes an encouraging update on cases of potential HIV cures achieved under different circumstances. These HIV-positive individuals received stem cell transplants to treat life-threatening cancers. The stem cell transplant donors possessed a rare genetic mutation that inhibits HIV from infecting cells, essentially equipping the recipients with a new, HIV-resistant immune system.
Timothy Ray Brown was the first individual to be cured of HIV by this approach, receiving the stem cell transplant in 2007. Brown died in 2020 from a recurrence of the cancer and is memorialized in the National AIDS Memorial Grove in Golden Gate Park in San Francisco.
In 2019, a second possible case was reported by Dr. Ravindra Gupta at the Conference on Retroviruses and Opportunistic Infections (CROI). Initially referred to as the London Patient, Adam Castillejo later publicly disclosed his identity. Castillejo has now been off ART for four years, and in the NBC News article Gupta states he now believes this represents a complete cure of HIV infection.
A third possible instance is a man in Düsseldorf, also reported at the 2019 CROI in a poster presentation. The researcher who presented the case, Björn Jensen, informed NBC News that the individual has now been off ART for three years with no evidence of HIV rebound.
The use of stem cell transplants is only appropriate in the context of treatment for certain cancers due to the risks associated with the procedure, but these outcomes add to the evidence that a complete cure of HIV may be achievable.