Accurate: It is accurate that a woman is in long-term HIV remission following a stem cell transplantation.
FULL CLAIM: Umbilical cord stem cells can be a cure for HIV; umbilical cord blood should be collected
REVIEW
The human immunodeficiency virus (HIV) has infected around 80 million people worldwide since the beginning of the HIV pandemic in the early 1980s. Untreated HIV infection results in acquired immunodeficiency syndrome (AIDS), which has claimed the lives of about 36 million people.
The HIV pandemic continues to be a problem. In 2020, there were 1.5 million new infections and more than 600,000 AIDS-related deaths. Although medical discoveries have led to treatments that significantly increase the life expectancy of HIV-positive patients, these treatments can only control the infection, not get rid of it.
However, there have been instances of people deemed to be cured of HIV following a procedure called stem cell transplantation, a procedure that is used in the treatment of blood cancer. At least two HIV-positive individuals, the “Berlin patient” and the “London patient”, achieved undetectable HIV viral loads after receiving a stem cell transplant[1,2].
And more recently in February 2022, the Washington Post reported that a woman was cured of HIV after receiving umbilical cord stem cells transplant. This is true; as the researchers monitoring the woman’s condition reported in a scientific abstract, the woman was transplanted with stem cells and achieved long-term HIV remission afterward: there was no detectable HIV in her blood up to 14 months after she stopped antiviral treatment.
However, a Facebook post interpreted these research findings to mean that that umbilical cord blood should be routinely collected as it can serve to cure HIV. After reviewing the claim, Health Feedback found that it missed important context that would inform the reader why stem cell transplantation as a possible go-to HIV therapy isn’t viable in most cases.
We first need to explain how stem cell transplantation works. This technique has two steps. First, the patient is subjected to high-dose chemotherapy or irradiation to wipe out their bone marrow. The bone marrow is the tissue responsible for producing white blood cells, so this preparatory procedure kills a large part of the patient’s white blood cells. This step is necessary to prevent rejection of donor stem cells by the patient’s immune system. Then, the patient receives an infusion of stem cells, which colonize and rebuild the destroyed bone marrow and start producing new white blood cells.
Because of the irradiation and chemotherapy and the subsequent transplantation, stem cell transplant is a lengthy and complex medical procedure with several potentially life-threatening side effects. The reason why the three patients qualified for stem cell transplantations is that they all suffered from blood cancer, and stem cell transplantation is a classic therapeutic option in those cases. The Berlin patient had leukemia, the London patient had Hodgkin’s lymphoma, while the woman had acute myeloid leukemia.
Carlos del Rio, professor of medicine at Emory University School of Medicine, told the Washington Post that “this is not a scalable intervention”. “A bone-marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured”, concurred Sharon Lewin, president-elect of the International AIDS Society. Therefore, it cannot be reasonably envisioned as a broad therapeutic option for HIV patients who don’t have blood cancer.
Furthermore, available results showed that stem cell transplants alone cannot prevent HIV from proliferating. HIV is known to infect a type of white blood cell called CD4+ T lymphocytes. Therefore it would make sense that a stem cell transplant that involves removing the infected T cells and replacing them with healthy, uninfected ones could clear out the virus from the body.
However, researchers tested this approach on monkeys with a simian equivalent of HIV. They found that the amount of virus in the monkey’s blood started creeping back up after the transplantation[3]. Thus, they concluded that stem cell transplantation alone cannot get rid of HIV. This was also confirmed in humans, when two HIV-positive patients—the “Boston patients”—underwent a transplantation using “regular” stem cells. The transplantation unfortunately proved unable to ward off the HIV infection.
The reason why this strategy proved successful in the Berlin, London, and the more recent U.S., patients is because their stem cell donors harbored a specific genetic mutation called CCR5-Δ32/Δ32. CCR5 is a protein present on the surface of the CD4+ T lymphocytes that HIV uses to latch onto the cells and infect them[4]. This is similar to the way SARS-CoV-2 binds onto the ACE-2 protein at the surface of cells[5].
T lymphocytes with the CCR5-Δ32/Δ32 mutation produce a truncated form of CCR5 to which HIV cannot bind. Therefore, people bearing that mutation are unlikely to become HIV-positive because the virus is unable to infect the cells and proliferate[6,7].
After the stem cell transplantation from their CCR5-Δ32/Δ32 donors, the three patients grew new bone marrow cells bearing that mutation and produced new CCR5-Δ32/Δ32 T lymphocytes that are protected from HIV infection. Therefore, the patients were made resistant to any remaining HIV that may have been dwelling in their body.
As the above demonstrates, this HIV treatment requires a donor with a very specific mutation. A study surveyed for the presence of CCR5-Δ32/Δ32 in 1.3 million potential donors[8]; they found that the frequency of people with that CCR5-Δ32/Δ32 mutation vary depending on the geographical area and found the highest frequency in the Faroe Islands where 2.3% of the tested individuals had CCR5-Δ32/Δ32. This is a rather low percentage, indicating that the mutation is quite rare, which means that the majority of umbilical cord stem cell donors won’t be suitable if curing HIV is the main goal. It is therefore unlikely that this approach will turn into a mainstream therapy for HIV infection. Therefore, it’s impractical to systematically collect umbilical cord fluid from babies with that objective in mind, as suggested in the Facebook post.
In summary, to date there have been three patients who benefited from a long-lasting HIV remission after receiving a stem cell transplant. However, not all stem cell transplantations can cure HIV. It worked in the cases of these three patients because the donor stem cells bore a rare mutation that makes the cells resistant to HIV infection. In addition, stem cell transplantation is a complex and risky medical procedure that cannot be scaled up to treat HIV-positive patients. The reason it was undertaken in these three patients was primarily to treat their cancer, not to treat HIV infection.
REFERENCES
- 1 – Gupta et al. (2019) HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature.
- 2 – Hütter et al. (2009) Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation. The New England Journal of Medicine.
- 3 – Mavigner et al. (2014) Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant. PLOS Pathogens
- 4 – Lederman et al. (2006) Biology of CCR5 and Its Role in HIV Infection and Treatment. Journal of the American Medical Association.
- 5 – Shang et al. (2020) Cell entry mechanisms of SARS-CoV-2. PNAS.
- 6 – Samson et al. (1996) Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature.
- 7 – Novembre et al. (2005) The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele. PLOS Biology.
- 8 – Solloch et al. (2017) Frequencies of gene variant CCR5-Δ32 in 87 countries based on next-generation sequencing of 1.3 million individuals sampled from 3 national DKMS donor centers. Human Immunology.
