Timothy Brown had HIV... and then did not

In South Africa alone, there are millions of HIV-positive people who wait for the day they will be able to utter the words, “I don’t have HIV anymore.”

The medical community has put aside the idea of curing this life-threatening disease, opting instead to focus on how to manage living with HIV. The cure for Aids can be likened to a mysterious alchemical formula that scientists have hoped exists, but have been unable to attain.

Researchers have spent thousands of man-hours and millions of dollars in an effort to develop a cure for this untamed disease. Thus far, research has only managed to come up with medications that allow infected people to live productive lives, but not to cure it.

However, this all changed for Timothy Brown when he was treated for leukaemia in 2007.

The story is quite remarkable. Brown was an ordinary man living in Berlin. He discovered he had contracted HIV in 1995 and was told he would be lucky to have two years to live.

Fortunately for him, antiretroviral (ARV) medication had started to become more readily available. For the next 10 years, he was living a healthy life on the medication. He was young, outgoing and gregarious.

In 2006, on a trip to New York while attending a wedding, Brown began to feel “miserable”, but attributed it to jet lag. He returned home, but he found the feeling persisted. A visit to the doctor revealed he had leukaemia.

Referred to Charité – Universitätsmedizin Berlin, he was treated by Gero Hütter, a specialist in blood cancers. Chemotherapy was recommended as a treatment, but it failed to eradicate the cancer. The only option left was a stem cell transplant from a bone marrow donor.

While ruminating on Brown’s case, Dr Hütter recalled hearing about a certain group of people who were naturally resistant to HIV.

These people in question carried a mutated CCR5 gene, called Delta 32. Because almost all strains of HIV use the CCR5 receptor to enter a host cell, the mutation confers resistance to HIV infection. It is believed by some that the immunity to HIV comes from surviving the Great Plague (1665–1666) when the survivors developed an immunity that has carried on to their heirs today.

Interestingly enough, about 1% of Caucasians are immune to HIV.

Dr Hütter had an idea to use Brown’s stem cell donor to cure the leukemia, but at the same time cure his HIV. The idea seemed preposterous.

In an interview with New York Magazine, Dr Hütter exclaimed: “My first thought was, ‘I’m wrong. There must be something I was missing’.”

Most of the HIV experts with whom he had consulted had accepted that a cure was impossible – not merely out of reach, but impossible.

Despite that, Dr Hütter decided to press on with his idea. He located 232 donors around the world to test for bone marrow compatibility and convinced the bone marrow registry to test for the mutated CCR5 gene.

“The main problem was that I was just a normal physician – I had no leading position. It was not always easy to get what we needed,” he says.

The tests cost money, and Dr Hütter’s laboratory paid for them out of their own budget.

Miraculously, the registry found one compatible donor who had the gene: Donor 61.

What makes this story all the more extraordinary, is that when looking for bone marrow donors for transplants, doctors usually start with family members first. Going outside the family carries risk, as unrelated donor transplants can result in graft-versus-host disease, where the receiver of the cells can develop an intolerance to the new transplanted cells, which can be fatal. Needless to say, the operation, while innovative, was extremely risky.

In February 2007, Brown had his first stem cell transplant from Donor 61, the first time an operation like this occurred. He stopped taking ARVs the day of the operation.

The surgery seemed to have been a success. “I went back to work, started working out at a gym and riding my bicycle again,” he said.

For a year Brown continued with his life, cancer-free. But in 2008, he relapsed – his leukemia had returned.

Dr Hütter did another transplant using tissue from Donor 61. This time the operation was a complete success. Subsequent testing and examination proved astounding: Not only was Brown completely cured of his leukemia, he was no longer infected with HIV. He has been dubbed the “Berlin Patient”.

Doctors are monitoring him at San Francisco General Hospital and at the University of California, San Francisco.

Brown has had countless biopsies. Doctors have samples of his blood, his brain, his liver and his rectum, and have run tests on these repeatedly. At the time of writing, there is no longer any evidence of HIV in his body.

Most people treated with ARVs continue to have the virus hidden somewhere in their bodies; countless sensitive tests have been run on Brown and no trace of the virus has been found anywhere in his system. Even levels of HIV-specific antibodies have declined. Since the transplant, he effectively no longer has a CCR5 receptor, which means that even if the virus were still present in his body, it cannot take root.

Almost four years after his operation by a doctor with an unorthodox idea, Brown has not had HIV. He has what the doctor’s call a “functional cure”.

His case is of great importance to scientists and researchers, as it has opened the door to what the medical community has long discarded: a real cure for HIV sufferers around the world.

The initial introduction of ARVs had given hope that HIV could be cured, but later tests soon revealed that as soon as the medication was stopped, the virus returned.

The medication did not eradicate the disease; the HIV continued to hide in the body, in the liver, brain or gut, invisible to the immune system. With Brown being HIV-free since his transplant, the possibility of finding a cure is once again on the table.

This will not be an easy task because even though he has been cured of HIV, the road that led him there was, firstly, quite unique and extremely gruelling. The chemotherapy and radiation killed off the existing cells in his bone marrow, which allowed Donor 61’s cells to replace it.

Seventeen months after the second transplant, doctors suspected that the chemotherapy had infected Brown’s brain, and a biopsy was done. It was negative, but he suffered neurological problems. He was temporarily blind and had memory lapses.

He is still undergoing physiotherapy to help him with walking and with his speech. His friends say he has become blunter in his interaction, his personality has changed. Brown told New York Magazine that he is not as gregarious as he used to be, as he “no longer feels attractive”.

Despite all he has had to endure, he is willing to let himself be tested and probed so that others can be helped. That takes tremendous courage, selflessness and strength.

The cure, if developed, would need to exist without the need for a donor to facilitate mass production, be accessible to the millions who are suffering from HIV and be inexpensive. Following the results of Brown’s experience, the cure would have to suppress the production of CCR5-bearing cells. At the moment, research is focusing on achieving this through transplants where the CCR5 cells are removed from the cells before being implanted and, using gene therapy, the cells can be transformed into HIV-resistant cells through manipulation. Some of these treatments are already undergoing early human trials.

One of the main barriers to finding a cure is that researchers need to isolate the exact reasons Brown was cured of HIV. It is clear that the CCR5 cells need to be suppressed, but researchers need to figure out if the anti-inflammatory medication he was given played a role in the overall result. Tests need to be done to pinpoint the reasons the method worked on him, and how to adapt it to the rest of the world.

The other barrier to the cure is money. Pharmaceutical companies are not too keen on finding a cure, as it makes little financial sense.

Using a drug every day to keep yourself healthy enough to live with the virus is more profitable than being able to take one tablet or injection that will rid your body of the disease entirely. It sounds uncaring, but a cure does not fit into the pharmaceutical market.

It has to be taken into account that once a compound belongs to a particular company, it cannot be used by anyone else. The knowledge is then held in the hands of the company who owns it, to do with it as it pleases.

For example, American biotechnology company, Medarex, developed a compound which, according to researchers, has great HIV-eradication possibilities. In 2009, Mederex was bought by Bristol-Myers Squibb, which now owns the compound. Since the buyout, the compound has not been tested on HIV, but is being tested on cancer instead.

The Berlin Patient case has pointed all the relevant people in the right direction toward finding a solution to what was once thought to be an unattainable cure. That does not mean it will happen today or even tomorrow, but it does mean researchers and scientists have a starting point.

Saarah Smith