HIV and Aids: An Alert

World Wide, HIV and AIDS are becoming the most common and dangerous disease day by day. Do people really know what causes AIDS? How is it caused? Moreover, really whether it is a disease or a cause of a simple disease that leads to death. However, my dear associates, people still dwell in those believes that AIDS is contagious to touch, or sharing food or dwelling with AIDS patients. Isn’t it ridiculous to think about this condition and feel pity for those who are suffering out of AIDS?

So here, I would like to discuss a few necessary information about virus (a normal one) and a virus that causes AIDS.

Now the question arises what is AIDS.

The answer lies here; the full form of AIDS is acquired immunodeficiency syndrome. Yes a complicated name and as well as very difficult to understand what exactly, it is. In simple words, it is defined as, such a disease that is caused by a virus called HIV (human immunodeficiency virus) that step by step destroys the immune system of the human body i.e. it kills or destroys the white blood cells (WBC) of our body that acts as a soldier against any disease.

This WBC is also called as antibody and the foreign bodies that enter our body and causes disease are called as antigens.

Now here is something interesting I would like to share with you people, the patient or person who is HIV positive i.e. carrier of the virus is not an AIDS patient, unless the HIV virus, which has encountered the persons body, causes an infection. The infected person by HIV is AIDS patient. A normal HIV positive can live up till 10 years or more if the patient is taking care of himself/herself and getting the normal environment from their friend/family circle. These people need attention, affection and love so that they feel to live longer. Think every body, my request to my dear associates, take active part in teaching and enlightening people who surrounds you and those who are ignorant because, who knows any day & any time we can be among those people who suffer from AIDS or HIV positive and tolerate humiliation and negligence. So by these above description, I hope it is clear that HIV positive and AIDS are not same but the former being the cause of the later.

An HIV infected patient.

An Outline of Virus Structure

Viruses are small infective agents consisting essentially of nucleic acid (either RNA or DNA), RNA – ribonucleic acid and DNA -deoxyribonucleic acid enclosed in a protein coat called as Capsid. These capsid and nucleic core in combination are termed as Nucleocapsid. Some viruses have, in addition, a lipoprotein envelope, which may contain antigenic viral glycoproteins, as well as the host phospholipids acquired when the virus Nucleocapsid buds through the nuclear membrane or plasma membrane of the host cells. The whole infective particle is termed as Virion. In different types of viruses, the genome may be double or single stranded.

Structure of Nucleus core of HIV and its constituents:

Function of Virus and Their Life History

• Viruses are basically intra cellular parasites with no metabolic machinery of their own
• In order to replicate/grow/increase in number, they have to attach to and enter a living host cell-animal, plant or bacteria
• Then they use their metabolic processes
• The binding sites on the virus are polypeptides on the envelope or capsid
• The receptors on the host cell to which the viruses attach are normal membrane constituents- cytokines, neurotransmitters, hormones, integral membrane glycoprotein, ion channels etc
• Once in the host cell the nucleic acid of the virus enters they starts using the cell’s machinery for synthesising nucleic acid and protein and the production of new virus particles
• Some examples of host cell receptors utilized by this particular virus (HIV) are listed below

Some host cell structures that can function as receptors for viruses

Virus that causes AIDS is HIV. The virion in retroviruses contains reverse transcriptase (virus RNA-dependent DNA polymerase), which makes a DNA copy of the viral RNA. This DNA copy is integrated in the genome of the host cells and then it is termed as provirus. The provirus DNA undergoes transcription and forms both new genomic RNA and mRNA for translations into viral proteins. After translation, the mRNA gets attached to the host ribosome by protease action, which is contained in retrovirus. Now the assembly and budding takes place and the completed virus are released by budding and many can replicate without killing the host cell. Some RNA retroviruses can transform normal cells into malignant cells. HIV is an RNA retrovirus.

There are two viruses associated with AIDS: HIV-1 & HIV-2. HIV-1 causes most HIV infections worldwide and HIV-2 occurs in parts of Africa and India. In 2001, it is estimated about 20 million people had died of AIDS, 30 million were HIV positive and there were 16000 new infections daily. The epidemic is overwhelmingly centered mostly on sub-Saharan Africa where up to 35% of the adult population is infected with HIV.

Mechanism of Infection of Human Cell by HIV Virion

The RNA retrovirus or HIV consists of an outer envelope, which contains glycoprotein120. Inside the envelope, it contains a Nucleocapsid in which a pair of RNA, 1Integrase, Protease, and at the end of each RNA strand a reverse transcriptase is attached.

1. Binding of the retrovirus to the CD4 receptor of plasma membrane of host cell
2. Entry of the retrovirus to the human cell through plasma membrane of the host cell
3. After the entry of the retrovirus uncoating takes place where, the RNA strand with the reverse transcriptase, Integrase, Protease are released into the cytoplasm of the host cell
4. Reverse transcriptase makes a double stranded DNA copy of the viral RNA
5. With the help of the Integrase, the new DNA copy enters the nucleus and integrates with the host DNA, forming a provirus
6. Now the transcription of the provirus takes place inside the nucleus of the host cell. Thereby releasing one mRNA and genomic RNA.
7. The mRNA by translation attaches with the host ribosome
8. Now, with the protease, action of the retrovirus released in the cytoplasm of the host cell, the genomic RNA and the translated mRNA combines to form an assembly and budding
9. Thereby, the new virion of retrovirus is produced

Sources of Getting Infected by HIV

1. HIV mainly gets spread by body fluids such as blood and semen
2. Through syringe which has already been infected by HIV
3. Having sexual intercourse unknowingly with HIV infected person or it is also seen in homosexualism (anal sex)
4. It occurs mainly through sexual intercourse with multiple partners without taking any safety measures (condoms, but condoms are safe up to 40% according to the doctors)
5. It also occurs during any kind of blood transfusion especially in case of thalasemmia (as reported in Surat, thousands of thalasemmic children got infected by HIV)
6. HIV also occurs from a pregnant mother to the baby in her womb. In that case, it is suggested within 2-3 months of pregnancy if the mother is suspected of HIV positive by ELISA test then it is advised to abort the child.

Few Anti-HIV Drugs

There are two main classes of anti-HIV drugs: Reverse Transcriptase Inhibitors and Protease Inhibitors. Each class has a different mechanism of action. Reverse transcriptase inhibitors, inhibit the reverse transcriptase of the retrovirus to make a double stranded DNA copy of viral RNA thereby inhibiting the process of replication of retrovirus and the Protease inhibitors, inhibits the protease action which is released in the cytoplasm of the host cell by the virus from getting assembled and budding thereby inhibiting the replication of retrovirus.

Reverse transcriptase inhibitors and the protease inhibitors in combination are used in the therapy of HIV/ AIDS. As stated above the use of combination treatment changed the prognosis of HIV/AIDS. The combination treatment is known as highly active antiretroviral therapy (HAART). A typical HAART combination would involve two nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or 1 or 2 protease inhibitors.

With a HAART regimen, HIV replication is inhibited, the presence in the plasma of HIV RNA is reduced to undetectable levels and patient survival is prolonged. But the regimen is complex, as it has many unwanted effects, is difficult to adhere to and may well have to be life long because HIV will not have been eradicated. The virus will be lying latent in memory T cells, integrated into the host genome and forming a source for potential reactivation if the drugs are stopped. At present, there is no cross-resistance between the 3 groups of drugs; but it needs to be borne in mind the virus has a high mutation rate-hence resistance would be a problem in future. The HIV virus has certainly not yet been outsmarted. With all the 3 groups, unwelcome drug interactions can occur and there may be interindividual variations in absorption. Some drugs penetrate poorly into the brain and this could lead to local proliferation of the virus.

The nucleoside reverse transcriptase inhibitors include zidovudine (AZT), abacavir (ABC), lamivudine (3TC), didanosine (ddI), zalcitabine (ddC) and stavudine (d4T). HAART regimens are often given only by a list of these abbreviations.

The unwanted effects being Anemia and neutropenia in long term administration in case of zidovudine , gastrointestinal disturbances , paraesthesia , skin rash , insomnia,fever,headaches, abnormalities of lever function, myopathy, confusion, anxiety, depression, and a ‘flu-like syndrome are also reported. Moreover mouth ulcers, dose related neuropathy, nail changes, oedema of lower limbs and general malaise has also been reported. Pancreatitis has also been reported.

Non-nucleoside reverse transcriptase inhibitors are chemically diverse compounds that bind to the reverse transcriptase near the catalytic site and denature it. Most of these drugs are inducers, substrates or inhibitors to varying degrees of liver cytochrome P450 enzymes. Currently available drugs are efavirenz (EFZ) and nevirapine (NVP). The unwanted effects being rashes occur in about 17% of patient if not carefully monitored this may develop in some cases into life-threatening skin conditions: Stevens – Johnson syndrome or toxic epidermal necrolysis. Fulminant hepatitis has occasionally occurred. More common adverse effects are fever, headache and lethargy in case of nevirapine. In case of EFZ the unwanted effects being relatively mild and consist mainly of CNS symptoms (dizziness, confusion, dysphoria) which resolve as therapy is continued. Skin rashes occur in about 20% of the patients, 2% GIT disorder. Drug interaction could be a hazard.

Protease Inhibitors includes saquinavir (SQV), Nelfinavir (NFV), indinavir (IDV), ritonavir (RTV) and amprenavir (AMP). They are all given orally, SQV being subject to extensive first-pass metabolism. CSF levels negligible with saquinavir and highest with indinavir (76% of the plasma concentration). Nelfinavir and ritonavir are best taken with food and saquinavir within 2 hours of a meal.

Unwanted affects being GIT disorder may be associated with metabolic abnormalities such as insulin resistance, high blood sugar etc. Long term use may lead to an unusual redistribution of cutaneous fat: less subcutaneous fat, increase abdominal fat, breast enlargement etc. Raised concentrations of liver enzymes are reported with RTV and IDV. It may also cause paraesthesias around the mouth, in the hands, feet and patients taking IDV may develop kidney stones. Serious rashes including Stevens-Johnson syndrome has also been reported. All the drugs can increase plasma concentration of benzodiazepines.

Conclusion

From the detailed discussion and all necessary information, I would thereby, request all my readers to pay necessary attention to the sources of AIDS or HIV and take safety measures such as enjoying intercourse using condoms, before taking any IV or IM injections to check whether it is a new one or not and after the usage crush it. If in case of glass syringe, do not forget to boil it in 100 degree Centigrade for 20 minutes in a closed container. To the HIV infected mother the advice as given above in the sources of HIV please try to follow the advice, in case of any blood transfusion, check whether the blood is free of HIV. Thereby, I hope my knowledge will enlighten you as well as your surroundings through you people, as we know life is precious and prevention is better than cure.