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HIV Versus HAART: an Endless Battle?

Updated on June 19, 2014
The battle between HIV and HAART
The battle between HIV and HAART | Source

(Red ribbon symbolizes awareness to HIV infection and support for those people living with HIV around the world.)

Look at the picture . You'll see an HIV ribbon on the left embedded on a dry leaf which represents diminishing health; while on the right, you'll notice an HIV ribbon together with the antiretroviral drugs on a green leaf which represents a reclaimed vibrant health.

The arrival of Highly Active Antiretroviral Therapy (HAART) is one of medical research's achievements in controlling the drastic increase in mortality rates due to HIV infection. The revealing effects of HAART in people living with HIV include:

  • weakened actions and effects of HIV in infected individuals
  • recovered immune system
  • increased CD4 count
  • lowered viral load
  • reduced presence of opportunistic infections
  • inhibited progression to AIDS
  • significantly increased overall quality of life

To understand how HAART works and what contributes to its success requires many factors to be considered.

Source
HIV infected person before and after antiretroviral therapy.
HIV infected person before and after antiretroviral therapy. | Source

The fate of human HIV-infected cells without HAART intervention

HIV is composed generally of genetic material, proteins, specific viral enzymes, and a protective envelope. The genetic material is composed of two single-stranded RNAs that contain all of the genetic code and information needed to survive, reproduce and replicate.

HIV does not bind to just any type of cell in the body. The virus requires specific receptors on the surface of host cells to be able to attach itself, penetrate and release its contents into the human cell.

Proteins from the viral envelope are used primarily for attachment to the human cell. Different enzymes contribute in constructing another viral cell. Once the viral genetic material is infused into the human cell, reproduction of the virus will never stop until that cell dies.

The result of numerous destruction of white blood cells is weakened immune system and the occurrence of opportunistic infections—a declined quality of life.

Action of HIV enzyme reverse transcriptase
Action of HIV enzyme reverse transcriptase | Source

Viral enzymes needed to perform deception

There are three viral enzymes necessary to succeed in the generation of new HIV cells:

Reverse transcriptase

In order to trick the human cell, HIV uses this enzyme to convert its single-stranded viral RNA to double-stranded viral DNA (because DNA is the genetic material of the human cell; making a replica of host DNA will enable the virus to accomplish the replication instructions encoded in viral RNA). What a devious plan, isn't it?

Integrase

This is the second enzyme needed to perform the deceit. The successful transcription of HIV from viral RNA to viral DNA, the enzyme integrase will integrate the newly-transcripted viral DNA into the human DNA. In this condition, the human cell does not recognize the newly-incorporated viral DNA and even worse—the human DNA considers the viral DNA as its own genetic material. Now the viral DNA can execute into effect (freely) the generation of HIV components (viral RNA and viral proteins) without any inhibition.

Protease

This is an enzyme needed to assemble the newly-formed viral RNA and viral proteins to produce new HIV. Even though numerous new HIV cells bud and leave to infect another cell, the viral DNA will permanently remain in the host cell and continue its function until the cell dies; the cell dies without knowing the enemy's deception.

HIV in resting memory state
HIV in resting memory state | Source

Another fate of an HIV-infected cell—a Niche for Sleeping HIV!

There is another fate of HIV infected cells besides death. Those HIV-CD4 infected cells that managed to survive the effects of HIV adopt a resting memory state or into a latency state. In this condition, HIV in the latently infected cell manages to live ineffectual. Even though nonfunctional and non-reproductive, the viral DNA attached to human DNA—which is still competent for replication— remains unscratched and nevertheless capable of being reactivated and accomplishing immune system destruction.

Though the fate for the HIV-infected cell is studied and documented, still there's no reason not to hope. The understanding of the functions of these three enzymes provides the structural basis of antiretroviral drugs and the success of HAART in debilitating the capabilities of HIV to further destruct the immune system. The determination and the willingness of the medical researchers to help and procure a cure must not be underestimated.

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Glimpse of hope provides a better future

After HIV DNA is fused with human DNA, the human body provides a factory for viral replication, but when HIV is on the outside of the host cell or just recently bound to the surface of the host cell (but not reversely transcribed and integrated), the body's immune system still has the capability to detect it as an antigen. The problem is the faster actions and effects of HIV outwit the production of antibodies against the virus. Before the antibodies have been produced into the circulation, numerous HIV cells had already been created and HIV mutation more possibly existed—ready to destroy the outsmarted human defenses. Now, where is the hope lies in these sentences?

Using drug (prostratin) can result to: (1) activation of latent HIV; (2)  inhibition of new cell infection
Using drug (prostratin) can result to: (1) activation of latent HIV; (2) inhibition of new cell infection | Source

The hope lies when HIV is still on the outside of the cell—when the virus is not integrated into human cell. There's still the capability of producing antibodies against the un-mutated HIV cells. That those antibodies (no matter how sluggish and outmaneuvered they were formed) are still antibodies! This is the basis of many recent research studies done today—like the manufacturing of vaccines against HIV.

Another hope is the eradication strategy that can destroy HIV reservoirs and result in finding a potential cure for HIV. A certain drug will be used to reactivate HIV in the resting state and prohibit other CD4 cells to be infected. By this time, HAART can suppress the actions of awakened HIV and with combining efforts of immune system, the defense cells are capable now to destroy all HIV.

Source

Two or more antiretroviral drugs taken at the same time is called combination therapy.

Combination of three or more anti-HIV drugs is called Highly Active Antiretroviral Therapy (HAART)

HIV Enzymes
Major Type of Antiretroviral Drugs
Reverse Transcriptase
Reverse Transcriptase Inhibitors
Integrase
Integrase Inhibitors
Protease
Protease Inhibitors
GP 120 and GP 41 (glycoproteins)
Entry and Fusion Inhibitors
Each type of antiretroviral drugs is specifically designed to halt the function of specific HIV enzyme

The fate of human HIV-infected cell with HAART intervention

HIV antiretroviral (ARV) drugs are drug regimens that counteract the effect of HIV. Each antiretroviral drug is purposely and specifically designed to inhibit the action of each viral enzyme.

Highly Active Antiretroviral Therapy (HAART) is a combination of therapeutic effects offered by each specific drug to block a specific viral enzyme.

Antiretroviral drugs are classified as:

Reverse Transcriptase Inhibitors

Reverse Transcriptase Inhibitors are medications that block the enzyme reverse transcriptase. These prevent the transcription of viral RNA to viral DNA—without viral DNA viral replication is inhibited. These drugs include Nucleotide/Nucleoside Reverse Transcriptase Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors.

Integrase Inhibitors

Integrase Inhibitors are medications that block the enzyme integrase. These drugs obstruct the viral DNA from incorporating itself in human DNA—which also promotes viral reproduction failure.

Protease Inhibitors

Protease Inhibitors are drug regimens that block the enzyme protease, prohibiting the assembly of new HIV cells inside the host cell.

Fusion inhibitors

Fusion inhibitors are medications that block the binding and fusion of HIV to human cells (HIV's strength and capability to perform its function is when inside a host cell)—preventing cell infection and damage to the immune system.

The action of each type of antiretroviral drugs is to act against specific type of HIV enzymes and glycoproteins.
The action of each type of antiretroviral drugs is to act against specific type of HIV enzymes and glycoproteins. | Source

Drug resistance happens when the previously effective ARV drugs taken do not work anymore against the virus. The suppressed HIV replication and reproduction emerges again with potency due to HIV variants resistant to anti-HIV drugs.

Success from within

HAART success is well-documented. The understanding of how the specific ARV drugs work against the virus and the therapeutic combination of two or more drugs will and can contribute to a total adherence of people living with HIV to HAART, reducing HIV drug resistance (one reason why resistance to antiretroviral drugs occurs is non-adherence to HAART).

Most HIV-infected people take ARV drugs without knowing the importance and function of each drug in the battle with HIV. They just know it is an anti-HIV drug; and so adherence to HAART is not one of their priorities. But if the infected person acquires substantial knowledge of how HIV attacks the body and how HAART fights against the actions and effects of HIV (by incorporating considerable information in public health education for HIV-infected people), they will understand how important adherence is and the consequences of being non-adherent.

Source

The start of a cure for all diseases doesn't commence from things but it originates from within. HIV infected people must not be satisfied only to take ARV drugs without understanding the functions, the importance and consequences of HAART; and must not be content with the shadows of drug resistance.

Maybe it's time that basic but significant scientific knowledge does not only remain in the grasp of people in the medical field—how HIV attacks, how HAART battles with HIV, and how ARV drug resistance occurs. People living with HIV also have the determination and will power to help themselves; and thus possess strength to survive—strength that cannot be taken away from them.

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