For once, the healthcare world brings us good news: a team of researchers from the Johns Hopkins School of Medicine have announced that, for the first time, a woman may have been cured of HIV. Code-named “the New York patient,” she received a new type of stem cell transplant from a donor who was naturally resistant to the HIV virus.
Following the treatment, the patient was able to stop taking her HIV medication without the disease reoccurring. So far, she has been disease-free for 15 months.
Why Is HIV Hard to Cure?
Ever since HIV/AIDS first appeared, the general understanding was that HIV can’t be cured because the virus hijacks the immune system that is meant to combat it. This is because HIV will not just progressively destroy the T cells that produce antibodies, but it can also hide its genetic code inside lymphocytes.
Lymphocytes live longer than other immune cells, allowing the virus to lie dormant for years. As a result, HIV remission is usually not permanent, unless the patient continues anti-retroviral therapy for life. Otherwise, the virus can awaken at any time and begin infecting the body again.
It took nearly 20 years for the first HIV treatment to be available. When the first anti-retroviral medications were launched, the scientific community responded with great optimism. These medicines could stop the virus from replicating throughout the body and prevent the disease from progressing into AIDS.
Until very recently, interest in developing an HIV cure had dwindled, as it seemed much safer to manage the disease forever. The New York patient is just the third person in the world – and the first woman – to manage such a feat.
Who is the “New York Patient”?
Although her identity has not been released to the public, the research team at Johns Hopkins School of Medicine released some background info on the now-recovered woman. Her case was originally presented during the virtual Conference on Retroviruses and Opportunistic Infections.
She is a middle-aged woman of mixed race who was initially diagnosed with HIV in 2013. In 2017, she was diagnosed with acute myeloid leukemia. She was treated at the New York-Presbyterian Weill Cornell Medicine Cener by Dr. Jingmei Hsu and Dr. Koen van Besien, two stem cell-transplant experts.
Can HIV Be Cured Now? Here’s What the Researchers Did
In all known cases, the cure involves destroying the immune system with radiation, which would also kill the virus hiding in T-killer cells. Then, the immune system is “replaced” with a new one via bone marrow or stem cell transplant.
How was HIV cured for the first time?
All cured HIV patients so far had severe forms of cancer and HIV. The first and third patients had Acute Myeloid Lymphoma (AML), while the second patient had Hodgkin’s lymphoma.
In AML and Hodgkin’s lymphoma, the bone marrow begins producing large, misshapen, or abnormal red blood cells. One of the options to counter this is with a stem cell transplant, which allows the patient to regenerate “normal” bone marrow that will no longer produce diseased blood cells.
The first two patients received a stem cell transplant from an adult donor with a genetic mutation that made him naturally resistant to HIV. In this way, doctors treated both the leukemia and HIV infection simultaneously.
Bone marrow transplants are expensive, dangerous, and potentially toxic. Before receiving one, patients have to receive extensive radiation therapy to destroy their immune system; this is meant to prevent the body from rejecting the new stem cells. Total body irradiation can also kill any infected cells where HIV may be hiding but at a huge cost.
This method poses two problems: first, it is notoriously hard to find a matching donor for any stem cell transplant – let alone one where the donor is also resistant to HIV. The genetic anomaly that grants HIV resistance is extremely rare, occurring in less than 0.5% of the population.
The second main problem is that stem cell transplants have a high chance of failure. The first patient cured of HIV using this method, Timothy Ray Brown (originally known as “the Berlin patient”), developed graft-versus-host-disease, a severe complication that is often fatal. He remained HIV-free until he passed from leukemia in 2020.
The second person cured, Adam Castillejo or “the London patient,” remains healthy to this day.
What was done differently for the latest HIV cure?
With the New York Patient, the doctors at New York-Presbyterian joined forces with two pediatric infectious disease specialists: Dr. Deborah Persaud, from Johns Hopkins, and Dr. Yvonne Bryson, from the University of California, Los Angeles (UCLA).
They designed a new regime for the patient, known as a “haplo-cord transplant.” It consisted of alternating umbilical cord blood infusions with adult stem cell grafts.
Why? According to Dr. Persaud, umbilical cord blood cells offer three advantages:
- The stem cells in umbilical cord blood cells are still a partial “blank slate,” so matching a donor with a receiver is much easier.
- It’s a lot easier to test umbilical cord blood for the HIV-resistant gene.
- A baby can donate umbilical cord blood at birth without any pain (unlike donating stem cells from the bone marrow, which requires painful needles in the spine).
Umbilical blood cord cells have already been used for treating leukemia in children. However, they had not been used in adults before because they contain relatively few stem cells. This is why they were combined with adult stem cells, which could fill in the gap while the cord blood stem cells grew.
But wouldn’t you need two donors, then? Yes, but each one only had to be a partial match. This makes it easier to find appropriate donors for people of more diverse racial backgrounds, often under-represented in donor banks.
In addition, the gene that provides resistance to HIV is mainly found in people of northern European ancestry. This means that patients from other ethnicities would be unlikely to find a full match to provide HIV-resistant cells.
HIV Cure: Can We Expect One Soon at the Pharmacy?
It is still too soon to say “Mission Accomplished” despite renewed optimism. The treatment used so far is dangerous and expensive, and it will not be offered to the overwhelming majority of patients living with HIV.
Stem cell transplants are too dangerous for any large-scale clinical trials, and it is considered unethical to do them on people who don’t already have leukemia or certain types of lymphoma.
While this breakthrough treatment will open the gate for a few more people, we are talking about maybe a dozen candidates a year. Plus, there is still some uncertainty around the New York Patient. While she is currently home and symptom-free, there is still the possibility that a lone HIV-infected lymphocyte may have escaped the irradiation.
For Dr. Bryson, the results so far are exciting, but they will need to wait a couple of years before declaring the patient completely cured. If she remains virus-free for three or more years, her team could attempt a haplo-cord transplant in more people.
Healthcare researchers also hope that the knowledge gained through this case will help develop new methods for gene therapy. In turn, this could help create more efficient HIV drugs.
Can HIV be cured at an early stage?
The closest thing we have to a widely-applicable HIV cure is Post-Exposure Prophylaxis (PEP). This requires taking three different antiretroviral medications (combined into a single tablet) for at least 28 days immediately following exposure.The big catch is that patients need to start PEP 72 hours after infection at the latest. This is a very short window of time, and every hour counts. People who have had unprotected sex with an HIV-positive person or have been injured with a needle should head to an emergency room to begin PEP as soon as possible.
If you are at risk for repeated exposure to HIV infections, there is a similar regimen known as PrEP or Pre-exposure Prophylaxis. PrEP involves taking two types of antiretrovirals (rather than three) for an indefinite amount of time.
Researchers have been chasing an HIV cure for over 20 years. Will we see an HIV cure or vaccine by 2030? We hope so – and every success story brings us one step closer to it.
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