British Man Becomes Second Person Ever To Be Cleared Of HIV

The capacity of the HIV-1 virus to enter white blood cells depends on the CCR5 receptor. Transfusions of stem cells with mutated versions of this receptor have been used to apparently eliminate HIV from a patient for the second time. Christoph Burgstedt/Shutterstock

Twelve years ago an individual was functionally cured of HIV through a stem cell transfusion. Unfortunately, this stunning success has proven hard to replicate. Now, however, a second person has had no detectable virus in their blood for 18 months after a similar, but milder treatment, offering hope this could become available on a widespread basis. However, the team behind this success are advising caution, saying it is too early to call it a cure.

CCR5 is a white blood cell receptor that acts as an entry point for the HIV-1 virus, the more common form of the disease. People with two copies of the Δ32 mutation of CCR5 gene are resistant to HIV-1 infection. Since Δ32 is rare, receiving copies from both your parents is like winning a genetic lottery. Scientists have wondered, however, whether this good fortune could be shared around by injecting stem cells from people with two Δ32 copies into HIV patients.

This approach led to the remarkable case in 2007 where Timothy Ray Brown, known as the "Berlin Patient," was functionally cured of an HIV infection he had had for at least 13 years. Brown was treated using stem cells, effectively transplanting his immune system, because he had an unrelated cancer, and the chemotherapy was interfering with the antiretroviral drugs that had previously controlled his infection. Post-treatment Brown stopped taking drugs but the virus has still not returned.

Unfortunately, stem cell transplants are not only expensive, but dangerous. They typically require knocking down the body's immune system to prevent it turning on the foreign cells. Brown was only treated this way because his prospects were so dire otherwise. He also naturally had one Δ32 copy, and when similar efforts failed with other patients, there was speculation this, or some other rare feature of Brown's case, was required for success.

The new case, the "London patient", was diagnosed with HIV in 2003, and put on antiretrovirals in 2012. Later that year he was diagnosed with Hodgkin's Lymphoma and needed chemotherapy. To prevent the virus rebounding, he was given a double Δ32 stem cell transfusion, although initially this was combined with ongoing antiretroviral treatment.

Sixteen months after the treatment, he was taken off antiretrovirals. He has been tested regularly in the 18 months since, and so far not only is there no sign of the virus returning, but his white blood cells are not expressing CCR5. The case report has been published in Nature.

It is important to note a functional cure is not a complete eradicated cure. It means even though copies of the virus may still be hiding quietly in the body, which can't be fought or treated unless they are activated, the virus is at a level that is undetectable in the patient's blood.

“By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people,” Professor Ravindra Gupta of University College London said in a statement.

Nevertheless, the researchers are clear: “At 18 months post-treatment interruption it is premature to conclude that this patient has been cured.” Advice that has been widely ignored.

The exact treatment used here is unlikely to be repeated widely. Unlike for Brown, radiotherapy wasn't required and the London patient experienced far less severe consequences than Brown, but Gupta believes the chemotherapy used against the lymphoma was an essential part of its success, temporarily destroying fast-dividing cells so replacement could occur. For people without cancer, treatment with antiretrovirals in the long term is preferable to even a short combination of chemotherapy and stem cell transfer. Moreover, there aren't enough double Δ32 donors to treat everyone. There are currently 37 million people infected with HIV, 21 million are on antiretroviral treatment, but drug-resistant strains are becoming more widespread.

Nevertheless, Gupta hopes the work demonstrates the viability of other, less risky, CCR5 modifications, possibly through gene therapy.

Comments

If you liked this story, you'll love these

This website uses cookies

This website uses cookies to improve user experience. By continuing to use our website you consent to all cookies in accordance with our cookie policy.