The cure for HIV

There are just two cases where the killer disease appears to have been cured. Researchers are also looking for other genes that can block HIV

It’s been almost 40 years since AIDS was first identified circa 1981. There are just two cases where the killer disease appears to have been cured. Although the second case has not yet been declared a definitive cure, it is described as a “proof of concept” AIDS can be cured.

The disease is caused by the Human Immunodeficiency Virus (HIV), which attacks the immune system. HIV takes over and kills a type of white blood cell, CD4 T-cells, which protect the body from infection. HIV inserts itself into the cell and replicates, spreading through the body. 

HIV is transmitted via exchange of body fluids. Once a person is HIV-positive, meaning the virus is in the system, that person may survive without symptoms for many years. Once the immune system is shut down, the infected person has full-blown AIDS and is vulnerable to all infections. Most AIDS victims die of cancer, pneumonia, and other diseases.

About 40 million people are estimated to have died as a consequence of AIDS, and another 35-40 million HIV-positive people are estimated to be currently surviving. Close to 1 million deaths per year are still being recorded, and about 2 million new infections occur every year. That’s an improvement over the early 2000s, when over 2 million were dying every year. 

It would be no exaggeration to say that HIV changed global social and sexual mores. It literally decimated Southern Africa with over 10 per cent of the population infected in several countries. Anti-retroviral (ARV) drugs can suppress the disease and allow indefinite periods of survival. But ARVs don't eradicate the virus. ARVs destroy cells in which HIV is actively replicating, but HIV can go into hiding, stop replicating, and remain dormant until the ARV therapy stops. Then, HIV returns. 

The first “cure” was found in 2007. Timothy Ray Brown, an American living in Berlin, was HIV-positive and under treatment for leukaemia. Leukaemia causes an abnormal increase in white blood cells. Blood cells are produced by bone marrow. Leukaemia treatment can involve bone marrow stem cell transplants from a healthy person. This helps regenerate healthy blood, and create a new immune system. Bone marrow transplants are dangerous — the patient’s immune system must be destroyed, prior to the transplant. 

A few people possess a mutated gene called CCR5 Delta 32, which offers natural immunity to HIV. This is a rare mutation, found only in some northern Europeans. The normal CCR5 gene, which most people possess, is used by HIV to enter T-cells. HIV cannot use the Delta-32 mutated gene and cannot replicate in a host with two copies of the CCR5 Delta 32 gene (one inherited from each parent). Even one copy of Delta 32 seems to offer protection. Only about 1 per cent of northern Europeans possess a genome with both copies. 

Brown’s doctors at the Charite University Medicine Berlin, Kristina Allers and Gero Hutter, found a compatible donor with a Delta-32 mutation. Twelve years after the marrow transplant, the “Berlin Patient”, as Brown is called in medical journals, remains HIV-free, and living normally. 

A similar approach was tried with the “London Patient”, by doctors at University College London (UCL) and Imperial College London, together with teams from Cambridge and Oxford. The patient was diagnosed with HIV infection in 2003 and on ARV therapy. In 2012, when he was diagnosed with another cancer, Hodgkin’s Lymphoma. The team was led by Dr Ravindra Gupta. 

In 2016, after chemotherapy, the patient was given a bone marrow stem cell transplant from a donor with two copies of Delta-32. As of now, according to reports from the University of Cambridge, he remains free of HIV, 18 months after ARV was discontinued and three years after the stem cell transplant. Given the long periods, HIV has been known to go into dormancy, the doctors are cautious about calling this a cure, yet. 

But it does indicate that therapy based on swapping out CCR5 genes can work. Both patients were in desperate straits with AIDS and cancer and this approach of nuking the immune system via chemotherapy and then transplanting a mutated CCR5 gene is life-threatening in itself (apart from being expensive and complex). Compatible donors may also be difficult to find. 

But these two cases offer hopes of finding less dangerous means of putting immunising genes into HIV-positive patients, via genetic engineering. The recent experiment where Chinese scientist, He Jiankui, genetically modified twins, Nana and Lulu, was one such attempt to change CCR5. Researchers are also looking for other genes that can block HIV. After many years, there’s hope that HIV could be eliminated.