Timothy Ray Brown, a HIV positive man, was administered a blood stem cell transplant from bone marrow in 2007 to treat relapsed leukaemia. His oncologist actively screened the unusually high donor pool for a donor with a rare genetic mutation known to offer protection from infection with the Human Immunodeficiency Virus (HIV). Mr Brown remains in remission from his leukaemia and is touted as the first person in the world known to have ‘recovered’ from HIV as he has remained clear of the virus since.
Suggestions that blood stem cell transplants from similar donors be used to ‘cure’ HIV are an attractive option for a disease that affects so many but for which there is no cure. HIV or the Human Immunodeficiency Virus hijacks immune system T-cells, our defence against disease causing progressive failure of the immune system; this allows life-threatening opportunistic infections and cancer to thrive.
HIV is a retrovirus, an obligate parasite that uses the hosts genetic copying machinery, as it cannot copy is own genetic material. HIV is surrounded by a lipid envelope and membrane-bound proteins which must recognise and bind to a specific protein receptor called CD4 on the T-cell so that it can gain entry into the cell. Once inside, the viral envelope is removed by host cell enzymes exposing viral genetic ribose nuclei acid (RNA). An RNA attached enzyme, copies RNA into deoxyribonucleic acid (DNA) and the host immune cell is then tricked into reproducing the viral genome instead of its own DNA and newly released virus particles are able to infect adjacent cells. CD4 works in combination with another co-receptor protein CCR5 (and sometimes CXCR4); people with two copies of a called CCR5-delta 32 have remained resistant to HIV infection despite repeated exposure to the virus. Long-term survivors, people with HIV who continued to have a functioning immune system for ten to 30 years after infection and without medication, were found to only have a single mutation of the gene CCR5-delta 32 which explained the slower progression to HIV.
HIV can rapidly and easily mutate changing the shape of its surface proteins while replicating within a single individual and when transmitted from one individual, this rate of change is so fast that our immune systems and vaccine developers are one step behind the ability of the virus to produce new strains.
The currently available treatment is HAART or Highly Active Antiretroviral treatment decreases the amount of HIV in the body by blocking its entry into cells and rebuilds the immune system.
The stem-cell donor which was transplanted twice into Mr Brown was homozygotes-depleted and Mr Brown CD4 T-cells all carry the donor’s two copy CCR5 delta 32 mutation gene. Suggestions that blood stem cell transplants from similar donors be used to ‘cure’ HIV are being treated with extreme caution. This is a risky and sometimes fatal procedure requiring that the patient’s immune system is completely eliminated to allow successful transplantation. No recurrence of leukaemia or detectible HIV has been found in Mr Brown bloodstream or tissues where HIV is known to specifically lurk and while it is possible that the virus could induce disease in these tissues which include lymph nodes, the gut, brain, liver and heart, his immune system markers have returned to normal levels.
HIV vaccines are proposed as a potential preventative treatment. HIV vaccine trials by Canadian, US-Thai and Spanish researchers have established that using a “killed whole virus” technique is safe, with no side effects and can stimulate the production of antibodies to HIV providing a protective immune response. Larger scale population vaccine studies are needed but a safe, effective and widely available vaccine is unlikely to be present for at least another 15 years.
This one successful case does not scientifically prove that blood stem cell transplants are widely suitable as a treatment for HIV infection but the results do offer hope of alternative successful treatment.