Auto Immunisation Disease Syndrome (AIDS) emerged as a scourge in the final two decades of the 20th century. Patients afflicted with this disease had no chance of recovering from it and had to face this harsh reality with forbearance. The good news is about the breakthrough achieved in cutting this fatal disease and for just the second time since the global epidemic began, a patient appears to have been cured of infection with H.I.V the virus that causes AIDS.
The welcome development occurred after nearly 12 years to the day after the first patient known to be cured, a feat that researchers have long tried, and failed, to duplicate. The success came as a surprise but confirmed that a cure for H.I.V. infection is possible although the process is difficult and tedious. The medical opinion, however, is that the remission achieved is long–term and could well be termed as a cure.
The successful treatment in both cases resulted from bone-marrow transplants given to infected patients but the transplants were intended to treat cancer in the patients, not H.I.V and this is not a realistic treatment option in the future. Instead, powerful drugs are now available to control H.I.V. saving patients the cumbersome process of transplants that have harsh side effects that can last for years. Nevertheless, rearming the body with immune cells similarly modified to resist H.I.V. might well succeed as a practical treatment.
There is now a second patient whom doctors describe just as ‘London patient’ in view of medical ethics. Earlier a German doctor in 2007 described the first such cure as the ‘Berlin patient’ who was later identified as Timothy Ray Brown, 52, a resident of California. Prior to this case, in case after case, the virus came roaring back, often around nine months after the patients stopped taking antiretroviral drugs or else the patients died of cancer. The failures left scientists wondering whether Mr. Brown’s cure would remain a fluke.
Mr. Brown had had leukemia and after chemotherapy failed to stop it, needed two bone-marrow transplants. The transplants were from a donor with a mutation in a protein called CCR5, which rests on the surface of certain immune cells. H.I.V. uses the protein to enter those cells but cannot latch on to the mutated version. Mr. Brown was given harsh immunosuppressive drugs of a kind that are no longer used and suffered intense complications for months after the transplant. He was placed in an induced coma at one point and nearly died.
But in case of the London patient doctors have ensured that a near-death experience is not required for the procedure to work. He had Hodgkin’s lymphoma and received a bone-marrow transplant from a donor with the CCR5 mutation in May 2016. He, too, received immunosuppressive drugs but the treatment was much less intense, in line with current standards for transplant patients. He quit taking anti-H.I.V. drugs in September 2017, making him the first patient since Mr. Brown known to remain virus-free for more than a year after stopping.
Although the London patient was not as ill as Mr. Brown had been after the transplant, the procedure worked about as well: The transplant destroyed the cancer without harmful side effects. The transplanted immune cells, now resistant to H.I.V., seem to have fully replaced his vulnerable cells. Most people with the H.I.V.-resistant mutation, called delta 32, are of Northern European descent and relevant data indicate that they number about 22,000 such donors. So far 38 H.I.V infected people have received bone-marrow transplants from six donors without reported mutation.
The London patient is 36th on this list. Another one, number 19 on the list and referred to as the “Düsseldorf patient,” has been off anti-H.I.V. drugs for four months. The consortium’s scientists have repeatedly analysed the London patient’s blood for signs of the virus. They saw a weak indication of continued infection in one of 24 tests but say this may be the result of contamination in the sample. The most sensitive test did not find any circulating virus. Antibodies to H.I.V. were still present in his blood but their levels declined over time, in a trajectory similar to that seen in Mr. Brown.
The treatment regime is far from perfect and requires development of intense gene-therapy approaches to knock out CCR5 on immune cells or their predecessor stem cells. Resistant to H.I.V. infection, these modified cells should eventually clear the body of the virus. Several companies are pursuing gene therapies but have not yet been successful. The modification must target the right number of cells, in the right place — only the bone marrow, for example, and not the brain— and tweak only the genes directing production of CCR5.
It is expected that eventually scientists may be able to develop a viral delivery system that, when injected into the body, seeks out all CCR5 receptors and deletes them or even a donor stem cell that is resistant to H.I.V. but could be given to any patient. One important caveat to any such approach is that the patient would still be vulnerable to a form of H.I.V. called X4, which employs a different protein, CXCR4, to enter cells. Even if a person harbours only a small number of X4 viruses, they may multiply in the absence of competition from their viral cousins. TW
Dr. Fahd Ali is a medical practitioner in the US and is very active socially