Mississipi Baby event and future possibilities for HIV treatment

• INTRODUCTION:

Few months ago, many news channels and printing medias gave priority to a news which attracted many people towards it. It created a topic of discussion not only among health professionals but also to civilians interested in health progress. The news reported that a HIV infected baby was ‘functionally cured’ in Mississipi Medical Centre by Dr. Hannah Gay and her team almost accidentally. Is it really a great achievement into HIV treatment? Is our quest to find HIV cure coming to an end with this event ? Before talking about these straight away, lets talk about and be introduced to most unfriendly virus of mankind ‘HIV’.

What is HIV ?

Human Immunodeficiency Virus (HIV) is one of the member of lentivirus i.e. slowly replicating retrovirus. It infects vital cells in the human immune system and it may then allow life threatening opportunistic infections and cancers, resulting the infection to be fatal. Infection can be spread by the transfer of blood, semen, vaginal fluid, pre-ejaculate or breast milk.

Difference between HIV and AIDS:

HIV is a virus which infects our immune system and damages progressively with time. This is a type of virus which unlike other viruses once infects a human, never gets away. Acquired Immuno Deficiency Syndrome (AIDS) is a syndrome . A healthy person usually has a CD4 (White Blood Cell) count between 600 and 1200 but as it drops below 200, the persons immune system is severely weakened and s/he is diagnosed with AIDS even if s/he has not become sick from other opportunistic infections. If a person with HIV is diagnosed with opportunistic infections or cancers even if the CD4 count is above 200, he or she is said to have AIDS. Opportunistic infections can be PCP (a type of pneumonia), or KS (Kaposi Sarcoma), wasting syndrome (involuntary weight loss), memory impairment or tuberculosis (TB). Once a person is diagnosed with AIDS, s/he is always said to haveAIDS even if the Cluser designation4 ( (CD4) count goes up again or the infection defining AIDS is cured. Most patients die from opportunistic infections or malignancies associated with the progressive failure of immune system.

Brief Life Cycle of HIV Life cycle of HIV can be understood mainly through four principle processes :

1) Entry through suitable host : HIV can only replicate inside its host cell i.e. human cells. The virus reaches a cell that carries a special protein called CD4 on its surface . The spikes (made mainly by glycoprotein gp120) present in the virus stick to the CD4 and helps the viral envelope to fuse with the cell membrane. The HIV then releases its contents (nucleocapsid ) into the cell leaving the envelope outside.

2) Reverse transcription and integration :

The viral contents consists three main enzymes : reverse transcriptase, protease, and integrase . Reverse transcriptase begins the reverse transcription converting the viral RNA into DNA. The DNA is transported to the cell nucleus and the enzyme integrase facilitates the integration of viral DNA into host cell DNA. The HIV DNA integrated host DNA is known as provirus. This then becomes undetectable by immune system of the host.

3) Transcription and Translation:

Provirus may lie inactive for a long time but when it becomes activated, it treats HIV genes same way as host (human) gene. Proviral DNA transcripts into messenger RNA. Then mRNA is transported outside the nucleus which facilitates translation by which building blocks for new virus are synthesized .

4) Assembly, Budding and Release:

Newly formed HIV proteins and enzymes from mRNA gather together to form new viral particles. Protease cleaves longer protein into smaller core proteins needed to create infectious virus. The HIV particles are then released by budding from the host cell. They get the envelope by host cell membrane.

Newly matured HIV are ready to infect another cell and begin replication process again.

HIV replicates billions of times a day destroying host immune cells.

Management of HIV :

The management of HIV AIDS normally includes the use of multiple anti retroviral drugs. The use of multiple drugs acting on different viral targets is known as Highly Active Anti Retroviral Therapy (HAART). It helps to decrease HIV count in body , improve the immune system and prevent opportunistic infections. There are many approaches and mechanisms for treating HIV infections. Many drugs are available which target different stage of the lifecycle of HIV and a combination of drug are mostly preffered. Lets not discuss it in detail.

Why treatment of HIV is very complex ?

Many viruses such as viruses causing common cold and flu stay in the body for only few days but HIV do not leave once it is entered. We can see that many viral diseases are curable easily but HIV is not an easy case. HIV can be named as a clever virus, it has its own strategies so that it persists many years in an infected person. It infects the very cell (CD4) that is supposed to fight against the virus. It inserts its genes into the DNA of host cell so it is intimately associated with a variety of cells. This allows HIV to escape from patients immune system or from antiviral drugs. The viruses lie hidden in certain reservoir cells in the body that are not reached by current drugs. While spreading in infected individual, HIV undergoes changes. Hence many variants of HIV can exist even within a single person. So, its like we’re not treating one virus but many thousands of slightly different viruses and the fact that each of them integrated into host cells makes it even worse. Hence it becomes very hard job to get rid of all HIV totally from body or it can be said impossible till today. A realistic goal for HIV management is to suppress HIV so that it does not raise fatal diseases and is not efficiently transmitted to anyone else.

What is Mississipi Baby event and is it really a breakthrough ?

At mississipi medical centre, it was discovered that a child 2 and a half years old was ‘cured’ of HIV accidentally . After baby was born, it was found that mother was HIV infected. Hence the baby was infected as well. After this discovery , the baby was given three different medications to fight against the virus but follow up was interrupted. After one year, doctors found that the mother had alresdy stopped giving medication to the child. Doctors then ran tests to see how much HIV is presently left in the baby blood, no traces of HIV was found. They then declared that the child no longer require further medication.

But is this really a big one ?

Unfortunately, not. It does not seem to be that big. The mississipi baby became infected because the mother was not tested in early pregnancy. Had she been tested timely, the woman would have been put on antiretroviral drugs, the baby would have been safer and would have given a short course of drugs which almost certainly have prevented the transmission of HIV from mother to child. When doctors found that mother had HIV, it was too late for preventive measures to be applied which compelled them to go to plan B putting the baby on the full three drug combination directly. It is already known and established fact that the sooner the drug regimen supplied, the better is the result. Hence it seems that the drug hit the target at the right time and to the right degree and hence the virus disappeared. Hence the baby is said to be ‘functionally cured’ in which traces of virus may remain but they are inactive and cant be seen on blood. In this case, mother disappeared and discontinued medication for five months. Other babies would have been treated the same way but remain on the drugs. Now by this single case, they should not stop the drug. One HIV free baby may be exceptional, there may be reasons that this baby was different. The mississipi baby was unusual for rich countries because majority of pregnant women in rich countries are tested for HIV and most infections in baby are prevented but not in poor countries. In 2011, 300 thousands of babies were infected at birth hence it seems that this event will, therefore save thousands of lives there but the thing is that there is already a way of preventing these infections using drugs. Hence the problem is not how to do it but needs to be ensured that the drugs and medical staffs are in the right place at the right time. Any practical applications for curing HIV is still further.

Is it a first case of HIV being functionally cured ?

No, it is not. There was a patient in Berlin named Timothy Ray Brown ( now known as The Berlin Patient) and was functionally cured of HIV. His story was something different. He was suffering from both HIV and leukemia. He was 40 years old when he developed leukemia. He had been infected with HIV for more than 10 years and was keeping his infection under control with standard HIV regimen. The patient doctor, Gero Hutter used an idea. Since HIV gets reserved in WBC, why not to try to cure the patient of leukemia and HIV at the same time? Hence he took a donor who carried relatively rarer mutation called CCR5delta 32 for stem cell transplantation. People with this mutation lack functional CCR5 , the main receptor type which HIV most often uses to enter the host cell. After receiving the HIV resistant stem cells, his HIV dropped to undetectable levels. A year later, his leukemia returned and it needed second round of chemotherapy and a second infusion of HIV resistant stem cells. It was very harsh treatment. The patient suffered very heavy problems for this. But this doesn’t seem easy to cure other patients through the same procedure.

The mutation that has HIV resistance is relatively rare . A patient with leukemia cant wait very long for treatment and its not easy to find a matched donor who carries double mutation. It gives too much of sufferings to the patient.

Does Berlin patient event open the door for the cure of HIV ?

Yes, it is partially true but not right now. But this finding has given the hope that there is real possibility to cure HIV AIDS. It is not practical or desirable to submit relatively healthy people with massive chemotherapy and stem cell transplantation. Only few patients with HIV would want to go through the painful and life threatening cancer treatment that was part of this cure. So far, this is not applied to any other patients. But we can always search for a better idea. This event has definitely given us a new hope.

Future possibilities :

Unlike recently being used approaches in treating HIV, some researchers are now exploring the use of taking a patients own cells and genetically engineering them to fight against HIV and some results are exciting. Other researchers are using different techniques to alter stem cells to fight HIV. Until the Berlin patient, most experts considered all of these treatments unlikely to succeed. Now it seems to be like nearer to success.

COME ON SCIENTISTS, YOU’RE GONNA GET THERE !!!

REFERENCES :

en.wikipedia.com

www.sciencedaily.com

www.dictionery.com

www.google.com

www.avert.com

www.who.int aidssupport.aarogya.com

www.guardian.co.uk

www.medicinenet.com