Since AIDS, or acquired immune deficiency syndrome, was identified in 1981, there has been only one medically-certified cure. That occurred under unusual circumstances and it gave researchers an important clue about new ways to attack the disease. Recent advances in genetic engineering techniques have aided in this process. Some studies offer new hope of a cure for the 35 million estimated to be infected worldwide.
No disease inspires as much superstitious dread. So far, AIDS is estimated to have killed over 30 million people and it infects millions every year. It is especially prevalent in Sub-Saharan Africa.
Anti-retroviral (ARV) drugs suppress the disease and allow indefinite periods of survival. But ARVs don’t eradicate the human immunodeficiency virus (HIV), which causes AIDS. ARVs destroy cells in which HIV is actively replicating. But when HIV is hit by ARVs, it just stops replicating, goes into hiding, and remains dormant. When the ARV therapy stops, HIV returns.
HIV is transmitted through the exchange of body fluids. Common causes of infection (not necessarily in order) include unprotected sex, blood transfusions, sharing needles and so on. The associations with promiscuity and drug addiction make it hard to implement policies to stop HIV-spread. What works best is a combination of sex education and drug awareness programmes, coupled with easy availability of condoms and disposable needles. But in conservative societies like India, people object to sex education. Some religions also discourage the use of condoms.
Someone infected with HIV (HIV-positive) may survive years, without symptoms. The virus attacks a class of white blood cells called CD4 T-cells. It inserts itself into the cell and replicates. T-cells are part of the natural immune system. Once AIDS develops owing to HIV taking over T-cells, the immune system shuts down. Most AIDS patients die of cancer, pneumonia, or some other infection.
The new approaches involve inserting immune genes into HIV-positive patients, through genetic engineering of stem cells. Every researcher is cautious about claims of cures. The characteristic long symptom-less periods and HIV’s ability to hide can be cruelly deceptive. HIV-positive people are also vulnerable to quacks. Many charlatans, including a cross-dresser who teaches yoga on Indian television, have claimed at various times to have found AIDS cures.
Some people have natural genetic immunity for various reasons. Advances in understanding of genomes have helped identify some of the causes of immunity. Researchers have known for a while that a mutated gene called CCR5 Delta 32 offers natural immunity to HIV.
The mutation is rare and found only in a few northern Europeans. The normal CCR5 gene, which most people possess, is the receptor HIV uses to enter T-cells. HIV cannot use the Delta-32 mutated gene and, hence, cannot replicate in a host who has two copies of the CCR5 Delta 32 gene (one inherited from each parent). Even one copy of Delta 32 seems to offer some protection. Only about one per cent of northern Europeans possess both copies.
In 2007, Timothy Ray Brown, an American resident in Berlin, was HIV-positive and also under treatment for leukaemia. Leukaemia causes an abnormal increase in white blood cells and a drop in red cells. Blood cells are produced by bone marrow. One drastic treatment is a bone marrow stem cell transplant from a healthy person. This helps regenerate healthy blood with a good haemoglobin ratio, and a new immune system. It’s dangerous since the patient’s entire immune system must be destroyed prior to the transplant.
Brown’s doctors at the Charite University Medicine Berlin, Kristina Allers and Gero Hutter, found a compatible donor who belonged to that rare one per cent with the Delta-32 mutation. Five years later, after the transplant procedures, the “Berlin Patient”, as Brown is called in medical journals, is still HIV-free and doctors concur that this is a functional cure.
Bone marrow stem cell transplants are very dangerous and very expensive. The potential donor pool of Delta-32 is small. But the case led researchers to look for other ways to insert mutated CCR5 into HIV patients. They also started looking for other genes offering natural immunity and attempting to engineer new genes to offer immunity.
One experiment at the University of Pennsylvania inserted T-cells genetically engineered to search and destroy cells infected with HIV. It has given encouraging results in 43 HIV patients, whose own T-cells were removed, engineered and re-introduced into their bodies. This sort of adaptive T-cell therapy has also been used in diseases like cancer. One key advantage is a reduced danger of rejection because the cell isn’t alien.
In another trial, at the Davis Campus, University of California, researchers have been experimenting on mice, which have similar immune systems to humans. In this study, a cocktail of three anti-HIV genes, including an engineered mutation of CCR5, were introduced into blood stem cells. The genetically-engineered stem cells seem to have been successful at curing HIV-infected mice. Now the research team is seeking regulatory permission to move onto human trials.
A related development is the discovery by teams at the University of Northern California, and at the Albert Hospital in Melbourne, that some anti-cancer drugs can prevent HIV from going latent and hiding. In that case, drugs that kill actively-infected HIV cells could work at flushing it completely, while it was prevented from hiding.
All these studies are a long way from scaling up to and becoming standard procedures. But a combination of these approaches may eventually lead to a permanent cure for this scourge. For the first time, medical researchers believe that this is a genuine possibility.
