Acquired Immunodeficiency Syndrome (AIDS)
Acquired Immunodeficiency Syndrome or AIDS has become the biggest challenge for medical science.It is caused by a virus called Human Immunodeficiency Virus or HIV.Now AIDS is a disease of pandemic proportions and a cure or vaccine may be decades away.First reported in USA in 1981, the virus was isolated in 1984 by two scientist Robert Gallo and Montagnier working independently.By the end of 2005, about 40 million HIV seropositive individual were living in the world, which included 2.5 million children.The virus entered India in 1980 and from 1986 onward, the Indian Council of Medical Research has started the serosurveillance against HIV.Today India has the second largest number of HIV infected people.AIDS is also called opportunistic disease because HIV will depress the immune system of body and thus other disease causing organism can easily enter and infect the body.Here other disease are using the opportunity created by HIV, to invade and survive which will eventually lead to the death of an individual.
Transmission and Course of the disease
As we all know, majority of patients get HIV infection as a sexually transmitted disease.About 81% of people fall under this category.The next most common mode of transmission of HIV is through blood.When needles or instruments having the blood of a HIV patient is used again, the disease is easily transmitted.So the risk is high for patients who receive blood transfusion many times, for example hemophilia patients and also for drug addicts who use syringes.In the remaining cases of HIV transmission, the virus is passed from mother to fetus through placenta.About 32% of infants born to a HIV positive mother may get the infection.So these are the common ways by which HIV is transmitted.But we can’t rule out the possibility that the infection can spread through any medium if contaminated with the body fluids of a HIV positive patient.
So by transmission the virus enters the body.Now the virus will start to multiply inside the host body cells.But at this point, it cannot be detected easily and this period of time is called window period.The only way to find out the presence of virus at this time is to check the blood for virus capsid antigen p24.Starting from the infection the virus is dividing fast and after some months antibodies against the virus can be seen in circulation.This is called Seropositivity and it is the second stage of infection.But here also the person may look normal outside, though the virus is still inside the body.They can even transmit the disease to others at this stage.About 10% seropositive individual will go for the 3rd stage of AIDS disease within 5 years, about 50% will get AIDS within 10 years and about 90% enter into disease stage within 15 years.It is said that for each AIDS patient, there are 100 seropositive persons in the general population.Now the third stage of disease is where the symptoms appear.There will be various clinical manifestations and the immune system of the individual is depressed.Therefore when other disease causing organism enter the body, the body will not resist them and they multiply easily.When the infection continues, the condition may lead to death.Usually death will occur within about 2 years after entering the third stage.
Symptoms:
There are wide variety of symptoms for AIDS.Main symptoms include fever and lymphadenopathy.We know that in AIDS our immune system is getting depressed.So any of the non-pathogenic microorganism can enter and cause problems in our body.The main activity of such opportunist microorganism is to cause lesions in skin, gastro-intestinal tract, lungs, urinary tract and brain.Apart from this, when pathogenic organism enter,the symptoms caused by the respective disease will be amplified because of the lack of effective immune response.In India, main diseases which use this opportunity is tuberculosis and gastroenteritis.Also one common thing we can observe in all cases is that there will be weight reduction in HIV infection.
THE HUMAN IMMUNODEFICIENCY VIRUS
In 1981, five cases of Pneumocystis carinii pneumonia were reported in USA.This protozoa can produce pneumonia only in immunodeficient individuals.So based on the clinical manifestation, the disease was named Acquired immunodeficiency syndrome or AIDS.Later when the virus was isolated from the lymphocytes of AIDS patient, the virus was named Human Immunodeficiency Virus.By further analysis, it was inferred that a simian virus transformed into HIV virus.
Structure of HIV
Human Immunodeficiency virus belongs to the retrovirus group.They are RNA containing viruses that replicate with the help of an enzyme Reverse Transcriptase or RNA dependant DNA polymerase.This enzyme can make a DNA using the RNA and this DNA is incorporated into the host cell during the time of infection.The virus has a cylindrical core, containing two copies of single stranded genomic RNA.The other protein components in the virus are named according to the molecular weight.For example, protein having molecular weight 32,000 Daltons is called p32.The core of virus contains reverse transcriptase (p66 and p55), an endonuclease (p32), nuleocaspid protein (p9) and a protease (p10).The viral core is surrounded by the major capsid antigen (p24).The outer shell is composed of myristylated protein, the membrane antigen (p17).
Working of HIV virus
Once the virus is inside our body it will start to bind with the target cells.The binding is through a receptor mechanism where the gp 120 of the virus envelop will specifically bind with CD4 molecules on the surface of the target cells.Since CD4 acts as a receptor for virus, all the cells having CD4 protein is the target of HIV.The cells include T-Helper cells, Macrophages, Monocytes, Langerhans cells, follicular dentritic cells and glial cells.So majority of them are White Blood cells.We know white blood cells or WBC are the cells in our body which help to provide immunity.Thus by the attack of HIV on these cells our immunity is depressed.
When the HIV infect a cell, it will first enter the cell and reach the nucleus.There it starts to produce a DNA from its RNA using reverse transcriptase.This newly formed DNA will be introduced into the host cell DNA by using an enzyme called viral integrase (p32).So now the host cell will start to use this DNA and make copy of RNA from it.In short, by the HIV infection the host cell is literally reduced to a HIV virus production factory.The virus use the machinery of host cell to produce its own copy and it multiplies.The extra ordinary rate of replication can produce about 10 billion particles per day inside the host.The infected host cell lives only for a day and all the virus produced inside it move to other targets.In this way large number of our cells are destroyed.In other case, some host like macrophages and monocytes acts as a reservoir of HIV infection, which disseminate the virus to various organs including central nervous system.
We have seen how the virus infect a host cell and cause damage, but the greatest danger because of HIV infection is the destruction of a lymphocyte called Helper-T cells.It is because, for our immune system to act against any foreign antigen, this Helper T cell has to start the response reaction.Without helper T cells no immune response can be initiated and thus it play a pivotal role in the immunological system.When these helper T cells, which have abundant CD4 molecules in its surface are attacked by HIV, its count drastically decreases and the deficiency caused will lead to suppression of almost all the immunological effectors.Thus without helper T cells our immune system get paralysed and the body will not respond to any incoming foreign particles.Making use of this opportunity other disease causing pathogen will enter the body and cause disease.So the disease which could have normally stopped by our body, can now take over our body and in most cases can lead to death.To add to this problem, HIV can also cause decrease in T killer cytotoxic cells activity.In some cases that can lead to cancer.Also antibody response to the foreign antigen is suppressed along with the decrease in production of lymphokines such as interferons, interleukin-2.So a total shut down of immune system is taking place.This is summarised in the picture below.But if you are very lucky, you may survive all this because 1% of population are resistant to HIV infection!
Laboratory Analysis and Treatment
The primary test used to find out the presence of HIV virus is called ELISA.ELISA stands for Enzyme Linked Immuno Sorbent Assay.In this test antibodies created in the body against the virus proteins are detected.As the name implies, the antibodies are adsorbed in a ELISA plate and with the help of suitable substrate and enzyme the presence of antibody is detected in the blood sample.Once the particle is detected the sample is sent for confirmatory test called Western blot analysis.It is a blotting technique and here antibodies against 6 different components of virus are analysed.Thus its more confirmatory than ELISA.In general, we can also find that T-helper cell count is getting lowered.The normal level which is more than 400/cmm is lowered below 300 in AIDS patient.When disease progress, more decrease in count can be observed.In later stages the antigen, especially p24, also starts to arise.Now with latest technology its possible to find the number of HIV particles in blood and the method is called Real Time Polymerase Chain Reaction.
Once detected positive for HIV, the patient has to be subjected to treatment.As we all know that there is no absolute cure for HIV.But giving proper treatment will reduce the multiplication and symptoms of HIV virus and thus we can prolong the life of the patient.The main treatment is by using Reverse Transcriptase inhibitor.We know that Reverse transcriptase is an important enzyme of HIV and if we can inhibit its action, the multiplication of the virus can be prevented.In this treatment many analogue molecules of genetic material ae used.For example, nucleoside analogues, non-nuleoside analogues, nucleotide analogues etc…One of the other type of inhibitor used is Protease inhibitor.These are extremely selective for HIV protease.So they finally block the assembly and package of HIV particle.Currently we use all these drugs in a combination and the treatment method is called Highly Active Anti-Retroviral Therapy.We must heard of ART treatment in newspaper.Thus the virus load in the patients body can be reduced and the life span can be increased.
So now we have understood some basic facts about AIDS and HIV.This HIV virus is very unique.The mutation rate in this virus is very high and because of that a proper cure and vaccine cannot be made.Suppose you find a anti-viral drug for this virus.By the time you think of testing it in virus, the virus will be mutated to some other form.Thus its very difficult for scientist to develop a cure or vaccine for HIV.Still there are various research going and there is some ray of hope.A recent news report say that scientist have found a weak spot in HIV virus and they can destroy the virus by targeting that part.But still it would take decades before a complete cure and vaccine is available.So by that time, prevention is the best way to tackle this disease.We have to create public awareness and educate the people about AIDS and HIV.Avoiding extramarital relationship, testing blood before transfusion, proper sterilization and disposal of syringes are some of the remedies to stop this fast growing threat.At last lets hope that this virus don’t mutate anymore, because once it mutates to level which give it the ability to survive in insect like mosquitoes, it will spread like anything.So lets hope for the best and spread the message on prevention of AIDS.
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