studying the cure for hiv


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In Dec 12, 2010, Allers et al has declared that "Cure for HIV has achieved" in their finding published in one of the highly rated journal known entitle as "Blood". Evidences suggest that their claim hold water and has a potential to be one of the strategies to cure HIV rather than just treating HIV. So far, all the efforts to produce a successful vaccine against HIB has failed, which are marred with one problem or another. Somehow we can blame HIV itself for failure to develop a vaccine, because HIV turns out to be smarter to develop better and improved strategy to live successfully in the host. Various drugs has been developed which targets different stages of viral replication to control HIV infections, most of the anti-retroviral drugs are very effective to reduce viral replication significantly, but none of them are effective enough to control viral replication at all. This means while these anti-retroviral drugs are effective, they can bring down the viral replication to bare minimal levels, which can prolong life-span of HIV seropositive or HIV patient, eventually, with the deterioration of immune-system, HIV replication fails to control and patients will develop a full blown AIDS, which is certainly a final chapter of life of a HIV infected patient. So far, it can be easily said that in case of HIV infections that "HIV infections can be controlled only, cannot be cured". Scientists and physicians always hoped that one day we may be able to get a control over this menace. They are all working in this direction, but success seems like a farfetched reality.

HIV has been identified for the first time approximately 30 years ago in 1981, in the form of Pneumocytitis carinii pneumonia (PCP) among 5 patients, but at that time it was not known as HIV or AIDS. A concerted effort has lead to the identification of its causative organism by Luc Motaignier in 1984 for which he was awarded Nobel Prize in 2008. Its name as HIV was adopted in 1988 by International Committee on Taxonomy of Viruses, to avoid confusions among different names of the same virus. Since then HIV research has seen unprecedented growth and development, even though humanity has to see a possible cure for HIV.

In early nineties of last century, a very unusual phenomenon was observed among HIV patients. It was noticed that some individual have been exposed to HIV infections, but they remain HIV free even though they were not taking any medication to treat HIV. This observation was very intriguing with lots skepticism around it, which led to detailed study of this phenomenon. This is called as Natural Resistance against HIV infections. Initially it was thought that may be these individual needs a very numbers of HIV particle to infect them, so various experiment have been tried in laboratory. As we know that CD4 positive T-cells (cell type found in our blood under the category of White Blood Cells), so these cells were removed from these patients and infected in the test-tube or culture plates with various amount of HIV infective particles, but they failed to be infected even with very high concentrations. This observation has led to realize that apart from CD4 HIV also need some other receptor to infect the cells. These new receptors are now known as chemoreceptors. These chemoreceptors are of two types, i.e., CXCR4 and CCR5. On the basis of needs of chemoreceptors, HIV itself is classified into two types namely X4 and R5 types.

Detailed studies have shown that these individual have natural resistance because of mutation (in other words, these receptors are not normal or modified) in their chemokine receptor CCR5. Due to this change in CCR5 HIV losses its secondary receptor responsible for HIV infection or enetry of HIV into the cells. Since HIV cannot infects the cells, these individual remains HIV free, even though they have been infected with HIV at various occasions. The main reasons for this modulation in CCR5 receptor is deletion of 32 base pairs of DNA in their gene sequence, hence it is called as CCR5Δ32/Δ32. Some individual have been completely resistance to HIV due to mutation is homologous in nature, which mean both the copies of 32 base pairs are missing in these individuals. Some individuals are not resistant to HIV infection, but HIV infection progression is extremely slow in these individuals, because they are heterozygous in nature for 32 base pair mutation, which means they still have one copy of normal sequence while one copy of 32 base pair is missing in these individuals. So far, this mutation has been observed only in ~1-3% of Caucasian population, while it has not been reported in other races. This observation is of high significance for HIV infections, as it provides an opportunity to revisit the mechanism of HIV infections as well as possibility to find a cure for HIV. It is another debate and issue, that how to use this information, where to use this information to cure HIV. This observation has to wait for more than 15 years to see its implication for human health to cure HIV patient.

Gero Hutter has put this observation on trial in a HIV infected patients in 2007. This patient is also known as Berlin Patient. This patient was infected with HIV but HIV infection was in control, due to proper anti-retroviral treatment. But this patient was reported with acute myeloid leukemia and chemotherapy was tried with this patient. Chemotherapy was not very successful to control AML, while due to toxicity doctors has withdrawn the anti-retroviral medications. Withdrawal of anti-retroviral drugs has led to rebound of HIV infection in this patient. Chemotherapy could not cure AML, while withdrawal of anti-retroviral drugs has made a negative impact on HIV infection. So, only choice for the treatment was the bone marrow transplantation for this Berlin Patient. Geo Hutter was hematologist in this team, so he has taken a conscious decision to transplant this patient with CCR5Δ32/Δ32, because this particular kind of mutation is known to have lesser chances for GVHD (a phenomenon of bone marrow rejection in case of bone marrow transplantation) and since this mutation has been shown to be completely resistant to HIV infection. Therefore, this will be an added advantage for this patient to target two birds with one stone. One the one hand this patient can be relived from AML while on the other hand this patient will be spared with further HIV infections. This was a successful case of bone marrow transplantation of bone marrow. But it has left different question to be answered to ascertain the fact that is this method has potential to be used to cure HIV infection.

These concerns can be answered by waiting and watching the long-term survival of this patient.

The same patient was followed by team of doctors and scientist, as he survived for more than 4 years since the initial bone marrow transplantation. The results of this study is presented and published in a very famous scientific journal Blood by Allers in December 12, 2010. This team followed closely Berlin Patient for the effect of bone marrow transplantation and HIV infection. They have declared that "Cure for HIV have been achieved". In their study they find that now this patient has all the blood cells from donor bone marrow and do not have any cell of his own bone marrow, which shows the success of transplantation and this phenomenon is known as Chimerism in medical terms. They have also looked these cells in mucosal parts of the body, which means cells deep inside the body and tissues are also from donor bone marrow, usually it is a major concern in case of bone marrow transplantation. This patient was also tested negative for HIV RNA (from blood circulation) as well HIV cDNA (in cells which can be infected with HIV like T-cells and monocytes and macrophages), which means this patient do not show any signs of HIV infections. Since this patients was not taking any medication for HIV and complete absence of HIV, that means the bone marrow transplantation with CCR5Δ32/Δ32 has proven that these cells are resistant to HIV infection. To assure the long term latently infected cells are still there in this patient some of the cells from mucosal part of body were also tested for HIV with one of the most sensitive method turn out to be negative. At later stages brain cells potentially get infected with HIV, this patients also gone with brain surgery and that has provided an opportunity to test the presence of HIV in brain, which also turn out to be negative. So far most of the possible clinical test so far performed in this patient shows all the positive signs that HIV has been cured. Still there are some risks for this patient is that another type of HIV (i.e., X4) exposure could infect this patient and he may become HIV positive. For this certain precaution has to be followed by this patient and also some new drugs which can block CXCR4 receptors are available which could help this patient. Even though HIV is cured in this patient, but we have to still be careful to say it is going to happen until unless this therapeutic intervention can be tried successfully in more patients as well as we still need long-term follow up of Berlin Patient.

This technology has opened up a flood gates for numerous future possibilities to be looked upon to make them to successful end. One of the major drawback is this mutation exist only in ~1-3% of Caucasian population, therefore, there is not enough donors for ever increasing and longer living population of HIV infected individuals. So far, this has not been observed in other races, for which there are numerous economic and social reasons. Therefore, there is strong need of international funding agencies to start an active research program for identification of either natural resistance against HIV in other races or presence of mutation in other races. A future possibility for the availability of universal donor, but time will tell that how successful we could be to make this as a reality with the application of various biotechnological tools available to us. Gene silencing (a method which can silence a gene of our interest) could be a blessing for those patients who can have an access to sibling bone marrow for transplantation.

At the end, the message is, probably we are approaching towards a goal to cure HIV, that carries too much of significance in case of failures to develop HIV vaccines. Unavailability of successful vaccine against HIV will not provide any preventive measures against HIV infection, but soon we can say " HIV is not any more incurable, for some, if not for all".

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