Doctor : "…Mr. Ali, as per the test reports, I am sorry to say , you are HIV positive….
Ali : (Breaks into tears) …doctor please recheck the reports…
Doctor: Sorry . I am helpless, all the test reports confirm you are HIV+ .
Ali : Doctor, AIDS doesn't have any medicine right? If my family and friends come to know about this, they will not even talk to me, they will leave me. I have heard AIDS spreads by shaking hand also, how can I live such a cursed life, doctor? Better you give me poison ! (with breaking voice and tears)
Doctor: Wait my dear, don’t be hopeless. You are not alone. There are millions of people in the world like you and I have told you are HIV+, but never told you are having AIDS. Yes, it doesn't have proper medicine to cure completely, but it can be controlled. You are lucky that you have got to know about this at very early stage. Now if you take the drug properly, you ‘ll have a normal life span, and one more thing, it is not an infectious disease, so if your friends shake hands with you, take lunch there is no way of transmission until you involve in a physical relationship or your blood gets in contact with the other…"
HIV & AIDS :
So HIV is the cause of the resulting disease AIDS. In 2014 1.2 million people died of AIDS. But the difference with other viral disease with HIV is that once a person gets affected with HIV-1, he will carry it until the last day of his life. The only way to control this is to take regular Anti-Retroviral Therapy (ART) as prescribed by the doctor. AIDS is the extreme stage of HIV-1 infection when the body is no longer capable of defending the opportunistic diseases. The normal CD4+ T cell in a healthy person varies from 500 cells to 1600 cells per mm3 of blood. But when this number falls below 200 cells/mm3 one is supposed to develop AIDS.
Origin of HIV :
Molecular Mechanism of HIV-1 Infection in Human :
•gag :The gene product of gag are p17, p24, p9, p7 . These proteins are responsible for making the nucleocapsid of the offspring virus.
•pol : The gene products are p64( having Reverse Transcriptase and RNase activity), p51(having reverse transcriptase activity), p10 (protease activity that cleaves the gag precursor) and p32 (with Integrase activity).
•env : The resulting protein of this gene is gp 41 and gp 120. The gp 120 appears to play the most vital role to bind and interact with the CD4+ in T-cells while the gp 41 helps in the fusion process.
Among other six genes tat, rev and nef encode for regulatory proteins, vif and vpu code for proteins essential for virion maturation and the last one vpr encodes for a weak transcriptional activator.
Now let us consider the steps of HIV-1 infection in Human:
1) In the immune system both the T helper cell subpopulation and the macrophages play major role in defending the invading microorganisms. In case of HIV-1 , the transmembrane protein gp-120 on the surface of the virus can only interact with the CD4+ of the T helper cell as well as the monocytes. But, this interaction can’t turn to a successful attachment until a co-receptor helps. For T helper cell and macrophage it is CXCR4 and CCR5 respectively.
2) After the successful attachment the fusogenic domain of gp 41 and the G-protein coupled co-receptor (CXCR4 or CCR5) on the target cell enables the fusion of the plasma membrane with the virus capsid. Then the viral genome along with the enzyme machinery enter the cell keeping the coat outside.
3) After getting into the cell the reverse transcriptase makes RNA-cDNA hybrid from the information of ssRNA template. Next the original ssRNA template is degraded by ribonuclease and 2nd DNA strand is made to form dsDNA.
4) Then the viral ds DNA is translocated to the host cell nucleus and integrated into the genome by the integrase enzyme forming a Provirus stage.
5) The viral transcription factors now stimulate the host cell transcription and make ssRNA followed by the translation to make necessary proteins.
6) Next the ssRNA assembles with the proteins including gp 41 and gp 120 and buds out forming viral coat. Finally they release bursting the host cell.
This way the main two warrior of the immune system starts dying and the whole body becomes susceptible to opportunistic infections leading to AIDS.
The Symptoms :
1) Acute Stage:These are the symptoms appearing due to the natural response of the body to the infection within the 3-4 weeks of exposure and often referred to Acute Retroviral Syndrome. The symptoms include
• Flu with fever
• Sore on the throat
• Pain in the Muscle and the joints
2) Chronic Phase: After the acute phase which continues from few weeks to months, in the Chronic phase as the body tries to defend the HIV and able to do so to some extent mostly no or mild symptoms occurs. This lasts for about 10years. This is the stage where if the Anti Retroviral Therapy (ART) is taken a person can live his normal life span without developing AIDS.
3) AIDS : If no ART is taken HIV-1 keeps replicating and increasing their population by destroying the body’s natural defence system throughout the chronic phase. When they become successful in doing so in around 9-10years, the opportunistic diseases starts attacking, and actual symptoms of AIDS appears. Some of the symptoms are given below:
• Rapid loss of weight
• High fever with night sweats
• Extreme tiredness
• Swelling of the lymph glands in the armpits, groin, or neck
• Diarrhea mostly lasts for few 1-2 weeks
• mouth or genitals sores
• neurologic disorders like depression and memory loss.
Some very common opportunistic diseases at this stage are :
i) Candidiasis (caused by Candida albicans) : Sores in the mouth (thrush) appears.
ii) Vulvovaginal yeast infection that does not respond to treatment.
iii) Coccidioidomycosis (caused by a fungus called Coccidioides immitis): High fever.
iv) Cryptococcosis (caused by Cryptococcus neoformans) : This fungus enters through the lungs and cause pneumonia.
v) Tuberculosis (caused by Mycobacterium tuberculosis).
The Modes of Transmission of HIV-1:
Here is the list of possible modes of transmission:
A) Most Common Route:
• Sexual relationship between a HIV+ individual with an unaffected person is the most common way of HIV as reported till date. Among different sexual behaviour it is found that Anal sex is much more risker than the vaginal sex. In US most of the reported cases of HIV+ are the homosexual men.
• Also having multiple sex partner having high risk of transmitting HIV.
Here is a well documented video that will explain different modes of HIV transmission including some preventive measures that will be discussed later in this article.
• An infected mother can transmit HIV to her child during her pregnancy.
• By using syringe/needle that is already used by any HIV+ individual.
• At the time of blood transfusion or organ-transplantation.
• Any direct contact with the blood of the patient.
C) Impossible ways: Here is the misconceptions people have about the transmission of HIV. Genuinely speaking HIV is a virus and it cannot sustain outside the host cell environment. Even in semen it can hardly be viable 30sec outside the body. So, the following can never cause HIV-AIDS:
• Air or Water
• Mosquito bites or any kind of insects.
• Shaking hands or hugging a HIV+ individual
• Sharing Lunch-dinner in the same plate, this transmits LOVE not HIV.
How Do I Know, if I am Having HIV? Simple, Get Tested :
There are separate modes of diagnosing HIV infection. Some of those are discussed below.
1) Antibody screening test (Immunoassay): Most common test for antibody detection is ELISA (Enzyme Linked Immunosorbant Assay). It is having a sensitivity of 0.0001-0.01 microgram of antibody/ml of sample. The procedure of detecting HIV is shown in the image below.
This is generally done when someone is diagnosed positive for HIV infection. This is because of the regular monitoring of viral load from the base value keeps the doctor on track how the patient is responding to the Anti Retroviral Therapy (ART).
4) CD4 Count: Along with Viral load test constant monitoring of CD4 count is also done. CD4 count id the number of CD4+ lymphocytes present per ml of blood. As the viral load and CD4 count is inversely proportional , i.e. if the no of virus particle increases definitely the no of CD4 lymphocytes will be destroyed and the immune system will get weaker with time. So both keeps the doctor on track.
5) Antibody Differentiation test: This test is done to ensure that the HIV infection is due to HIV-1 or HIV-2 .
6) Rapid Test : These test are very quick and reliable for screening. These tests use fluid samples like blood, oral or vaginal fluid and gets the result within 20 mins. Presently a number of Rapid HIV test kits are approved by FDA. Below is a very short video on Rapid HIV Testing.
• Home Access HIV-1 Test System : This is an anonymous test. Here the patient will take the kit and after blood sampling send it to the FDA approved laboratory. The report can be obtained in the next 3-4 business days.
• OraQuick In-Home HIV Test : This kit gives very quick result at home.
How to face this Global Threat?--The Prevention:
1) Sexually transmission:
i) Take precautions like using condom (for both male and female).
ii) Don’t live a polygamy life and be honest to your partner.
iii) Live a sexually disciplined life.
2) Blood or other modes :
i) Screening blood samples. This must be done by the blood banks.
ii) Always use fresh needles or syringes.
In case of mother to child , testing should be done at the time of pregnancy. If the result is positive proper medication and advice should be taken from the doctor.
Above of all , if the report is positive for an individual , appropriate measures must be taken along with the full course of the Anti Retro Viral therapy as prescribed by the doctor.
Combat with HIV - The Anti Retroviral Therapy (ART) :
1) Blocking Reverse transcriptase action by Nucleoside and Non-nucleoside analogue: These are actually the nucleoside analogues that mimic the naturally occurring nucleosides. If these are incorporated into the growing chain of cDNA made by reverse transcriptase, there will be a chain termination and no functional cDNA will be made. Thereby stopping the lifecycle. Example of such FDA approved drugs are Zidovudine, or AZT (Azidothymidine).
2) Inhibitor of Protease : After the proteins are synthesized in the host cell , these need to be cleaved for making functional virus particle by the enzyme called Protease. These class of drugs inhibit the protease activity and thereby preventing the formation of new mature virion. Examples for such drugs are Nelfinavir (Viracept) , Indinavir (Crixivan) etc.
3) Inhibitor of Integrase : Scientists have developed drugs that can inhibit the integrase activity so that the viral dsDNA cannot integrate to the host cell genome. Currently FDA approved available drug for Integrase inhibitor is Isentress (generic name raltegravir) and Tivicay (generic name Dolutegravir). Researchers are still working on in this topic.
4) Fusion Inhibitors-Blocking the attachment of HIV to the Host cell : Research is going on to develop therapeutic agents to target both gp 41 and CXCR 4 / CCR5 and stopping them from activating the G-coupled receptor signalling pathway. Currently FDA approved available drug for Fusion inhibitor is Fuzeon (generic name enfuvirtide, T-20).
Though the mode of action of these drugs are different, one single drug is not effective to treat HIV. For this reason often in ART, a combination of the nucleoside analogues and protease inhibitors are used. This is designated as HAART (Highly Active Anti-Retroviral Therapy). The main disadvantage of using all these drugs is most are not HIV-1 specific. So, they once enter the host cell can equally affect the host cell machinery also and thus killing the host cell. Another point is that there are number of side effects seen in the patients taking ART.
A Look into the Current Research Scenario:
1) Developing more effective Anti-Retroviral Therapy : This is the traditional approach followed by various scientist since HIV epidemic. Till date there are six lines of anti-retroviral drug developed in total. Introduction of HAART (highly active anti-retroviral therapy) significantly reduced the mortality rate of HIV patients. Scientists of the The Aaron Diamond AIDS Research Center, New York under The Rockefeller University are committed to find effective ways to target HIV and improve the efficiency of ART.
A messege to the reader:
For More information and Current research You can visit:
2) CDC - Centers for Disease Control and Prevention, (http://www.cdc.gov/hiv/)
3) Aids.gov (https://www.aids.gov/hiv-aids-basics/)
4) U.S Food and Drug Administration (http://www.fda.gov )
5) National institute of allergy and infectious diseases (http://www.niaid.nih.gov/topics/hivaids/...fault.aspx)
6) The International AIDS Vaccine Initiative, New York (https://www.iavi.org)
7) Aids Info (https://aidsinfo.nih.gov/clinical-trials)