“It’s now almost exactly two years since we treated him and the virus is nowhere to be seen”
“Considering how bleak things looked a year ago, it is amazing to hear the word eradication”
Since discovery of HIV (Human immunodeficiency virus) in 1984 by Luc Montagnier of the Pasteur Institute in Paris and Robert Gallo of the National Cancer Institute in Washington DC, humans have been in a constant struggle to search for a ‘cure’ for this retrovirus; the cause of AIDS and deaths of more than 20 million people to date. So, how far have we advanced in 25 years??
Let’s look back in time to year 1995. Saquinavir, a protease inhibitor drug that results in defective HIV formation, was produced. This, along with previous less effective antiretroviral drugs such as AZT (zidovudine), a drug that stops the replication of HIV in our cells by stopping the action of the virus’ enzyme reverse transcriptase, initiated HAART (Highly Active Antiretroviral Therapy). For the first time, patients had access to a reliable treatment of HIV, using a ‘cocktail’ of drugs (generally 3). The possibility of HIV becoming resistant to such treatment is unlikely as it will have to mutate 3 times simultaneously against the 3 different drugs used. By taking a couple of pills a day, AIDS progression can be discontinued. Yet, their high cost, side-effects and inconvenience of taking them everyday compels for new, better treatments to be developed.
November 2008 – a true breakthrough for modern HIV treatment was announced; through a bone marrow transplant to treat Leukaemia, a 42-year old German patient was cured of AIDS. How is this possible?
In the mid 1990’s it was first discovered that natural genetic variation in some people’s immune systems meant that some people are naturally immune from HIV. These individuals have mutations in the gene of CCR5 of CD4 white blood cells, resulting in the loss of 32 amino acids in the gene (delta32 mutation).
In a normal situation, HIV binds to the CCR5 molecules on the surface of CD4 cells which then allows it to enter and invade the cell. However, in individuals with such a mutation, the mutated CCR5 molecules never reach the surface, and as a result, HIV is unable to invade their CD4 cells. Such is the case here with the bone marrow transplant.
When the transplant occurred, the man’s own immune system was destroyed due to the chemotherapy, and he received the HIV-resistant cells from the bone marrow of the donor.
So, what do all this point towards?
Unfortunately, repetition of such an event is rather unlikely. Bone marrow donors are rare and those with HIV-resistant cells are even rarer. Ultimately, it is perhaps unethical to give a non-leukaemia patient a bone marrow transplant.
Luckily however, we have alternative ways to make use of this new discovery. Currently, several related gene therapy projects are underway.
One of these is a project by Sangamo Biosciences of Richmond, California. First CD4 cells are extracted from patients, harmless viruses are then added to these CD4 cells which carries genes that code for artificial ZFNs (zinc finger nucleus). The modified CD4 cells then produce ZFNs, which disrupts the CCR5 genes. Finally the cells are inserted back into the patients. The idea is that the modified CD4 cells will replicate faster and live longer than HIV-infected ones and eventually become dominant. The results have been tested and shown to be positive on HIV-infected mice. Philip Gregory of Sangamo suggests that in the future modification of the stem cell CD34 might prove to be even more effective as stem cells are capable of becoming every type of white blood cells thus the entire immune system can become resistant to HIV.
John Rossi, director of the City of
Ultimately, at the end of the day, gene-therapy using HIV-resistant CD4 cells is still in an experimental step and it will be many years before it will actually be able to be put into practice in regular clinics. However, this discovery leads to alternative ways to combat HIV, and points towards a future in which we will no longer need to rely on drugs in our struggle against HIV.
Blog written by student number 42005434
References:
Andy Coghlan, “One shot to rid body of HIV”, 18 February 2009, NewScientist Volume 201 No. 2696.
Available online at: http://www.newscientist.com/article/mg20126964.400-gene-therapy-promises-oneshot-treatment-for-hiv.html?full=true
“Suddenly there is hope that HIV can be defeated”, 18 February 2009, NewScientist Volume 201 No. 2696.
Available online at:
http://www.newscientist.com/article/mg20126963.200-new-hopes-over-elimination-of-aids.html
Clare Wilson, “NO MORE AIDS”, 19 February 2009, NewScientist Volume 201 No. 2696.
Available online at:
http://www.newscientist.com/article/mg20126966.100-are-we-about-to-eliminate-aids.html
Andy Coghlan, “Gene therapy for HIV shows promise”, 15 February 2009,
Andy Coghlan, “HIV ‘cure’ won’t save millions”, 14 November 2008,
“Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation”, 12 February 2009, The
http://content.nejm.org/cgi/content/short/360/7/692
“Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells”, 15 February 2009, Nature Medicine,
http://www.nature.com/nm/journal/v15/n3/abs/nm.1932.html
John Pickrell, “Timeline: HIV and AIDS”, September 2006,
http://www.newscientist.com/article/dn9949-timeline-hiv-and-aids.html?full=true
John Pickrell, “Facts and Figures: HIV and AIDS”, September 2006,
http://www.newscientist.com/article/dn9947-facts-and-figures-hiv--aids.html
Julie Clayton, “Beating the odds”, 8 February 2003,
http://www.newscientist.com/article/mg17723814.500-beating-the-odds.html?full=true
