Human immunodeficiency virus (HIV) damages the cells in the immune system, reducing the number of some of the white blood cells (CD4+ T cells) in the body and weakening the ability to fight everyday infections and disease. If left untreated, HIV infection eventually progresses until the immune system is too weak to defend against cancers and life-threatening infections, leading to acquired immunodeficiency syndrome (AIDS) within 2 to 15 years after infection. Without treatment, people with AIDS typically survive for 3 years.
Since the first reported case of HIV in 1981, over 25 million people have died and millions of people are infected each year, being one of the most significant health and social problems facing the modern world.
In recent years there have been many advances in HIV treatments and therapies that have dramatically improved the quality of life of people with HIV. Indeed, treatment can control HIV and enable people to live a long and healthy life with undetectable viral load. However, HIV infection remains incurable due to the permanent integration of HIV into the host cellular genome.
Interestingly, there is a rare group of HIV-positive individuals, referred to as “elite controllers”, who maintain undetectable viral loads in the absence of any treatment, without ever progressing to AIDS. As mentioned, this happens very rarely and early studies were not successful in finding common causes for protection.
So far, although there is no effective cure for HIV, only one person in history is considered to have been effectively “cured” of HIV infection:
The Berlin patient
Timothy Ray Brown (The Berlin patient) was diagnosed with HIV in 1995 and diagnosed with acute myeloid leukemia in 2006, a cancer that affects white blood cells. To treat the leukemia, doctors first used chemotherapy and radiation to kill virtually all of his white blood cells and then, the patient received a hematopoietic stem cell transplant from a donor to give him the stem cells necessary to develop new white blood cells .
When choosing a bone marrow donor, doctors selected an individual with a rare mutation that alters one of the main co-receptors (CCR5) HIV uses to get inside white blood cells, resulting in a mutated CCR5 protein. Therefore, the patient’s own immune system was destroyed by chemotherapy and radiation, killing most of the HIV infected cells in his body and then replacing them with cells from a donor with the CCR5 mutation, resulting in a new immune system full of HIV-resistant cells.
Until now, this success had not been reproduced in other HIV-infected patients, mainly because of the small minority of viruses that use alternative receptors, such as CXCR4. However, more than a decade after the Berlin Patient, a new study recently published in Nature described a second patient free of HIV after stem-cell therapy: The London patient, suggesting the first case was not an anomaly.
The London patient
The London patient, who is remaining anonymous, was diagnosed with HIV in 2003 and advanced Hodgkin’s lymphoma in 2012. Again, after chemotherapy, the patient was treated with stem cell transplants from a donor who carried a mutation in CCR5, making his white cells resistant to HIV and being in remission for 18 months since he stopped taking antiretroviral drugs.
These two patients were “functionally cured” or “in remission”, meaning that they don’t have to take medications and the viral load is undetectable (no HIV can be measured). However, it is too early to say they have been completely cured of HIV.
Therefore, although the method used is not appropriate for the millions of people around the world living with HIV because of HIV viruses using alternative receptors to CCR5 and the toxicity of chemotherapy and transplant-related side effects. The Berlin and London patients are the strongest proof that HIV can be “functionally cured”, offering hope for new future treatment strategies, including gene therapies.
Further reading and sources:
Past, present and future: 30 years of HIV research
The London Patient: HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation
The Berlin patient: Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell TransplantationSecond patient free of HIV after stem-cell therapy