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The HIV Life Cycle:

How Untreated HIV Progresses

Once you’re infected with the HIV virus, it most commonly attacks your T-cells, which are also known as CD4 cells. When one of these cells is infected, and if it is untreated, it goes through several steps to reproduce and copy itself to create more of the virus.

The HIV life cycle process is commonly broken up into the following steps:

Binding and Fusion:
This is the process by which HIV binds to a specific type of CD4 receptor (a protein present on the outside of infection-fighting white blood cells, CD4 receptors allow HIV to fuse to and enter cells) and one of two co-receptors (another protein, one known as CCR5 and the other known as CXCR4) on the surface of the CD4 cell. Once this occurs, HIV can fuse with the host cell (CD4 cell) and release its genetic material, its RNA, into the host cell.

HIV drugs that are used to block this particular step are called Entry Inhibitors. Entry Inhibitors work by preventing HIV from entering healthy T-cells. There are currently two FDA approved Entry and Fusion Inhibitors – Selzentry and Fuzeon.

Reverse Transcription:
An enzyme called Reverse Transcriptase changes the genetic material of the virus (from single-stranded HIV RNA to double-stranded HIV DNA) so it can be integrated into the host DNA.

This Reverse Transcription process can be blocked by two HIV drug categories: Nucleoside Reverse Transcriptase Inhibitors (NRTIs or Nukes) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs or Non-Nukes).

There are currently 7-different NRTIs approved for use by the FDA, two of which are considered “Preferred” – Emtriva and Viread.

Four different NNRTIs are approved by the FDA. The “Preferred” drug in this category is Sustiva.

The drugs in these two categories are also co-formulated with drugs from other HIV-fighting categories in single-pill regimens such as Atripla, Complera and Stribild or combination pill regimens like Truvada.

Integration:
The virus’ new genetic material enters the nucleus of the CD4 cell and uses an enzyme called Integrase to integrate itself into the host cell’s own genetic material, DNA, where it may “hide” and stay inactive for several years producing few or even no new copies. This integrated HIV DNA is called Provirus.

The drugs in this HIV drug category that are meant to stop this process are called Integrase Inhibitors. Isentress and Tivicay are “Preferred” by the FDA. One new drug is awaiting approval in this category – Elvitegravir, is already present in single pill, once-daily Stribild.

Transcription:
When the host cell receives a signal to become active, the provirus uses a host enzyme called RNA polymerase to create copies of the HIV genetic material and shorter strands of RNA called messenger RNA (mRNA). The mRNA is used as a blueprint to make long chains of HIV proteins.

Assembly:
An enzyme called Protease cuts the longer HIV proteins into individual proteins. As the smaller HIV proteins come together with copies of HIV's RNA genetic material, a new virus particle is assembled.

This viral assembly can be blocked with the HIV drug category called Protease Inhibitors. There are currently 8-drugs approved by the FDA in this category. Reyataz and Prezista are listed as “Preferred” in this category.

Budding:
This is the final stage of the virus’ life cycle. The virus pushes itself out of the host cell, creating “buds,” taking with it part of the membrane of the cell. This outer part covers the virus and is covered with protein/sugar combinations called HIV glycoproteins. These HIV glycoproteins are necessary for the virus to bind CD4 and co-receptors. The new copies of HIV can now move to infect other cells.

Stages of HIV
The HIV virus has a progression. It’s important to understand that if you are infected with HIV, you don’t have Acquired Immune Deficiency Syndrome (AIDS). However, if you don’t get treatment, HIV will eventually overtake your immune system—and this will lead to your being diagnosed with AIDS. Here are the common stages of untreated HIV:

Acute Infection: Within 2-4 weeks after being infected with HIV, you can experience an acute illness that can often feel like severe flu symptoms. This is called Acute Retroviral Syndrome (ARS) or Primary HIV Infection and it’s the body’s natural response to fighting the HIV infection. According to the U.S. Department of Health and Human Services, not everyone develops ARS and it can take up to 3 months for it to appear in some people.

During this period of infection, large amounts of virus are being produced. The virus uses CD4 cells to replicate and destroys them in the process. Because of this the CD4 count can fall rapidly. Eventually the immune response will begin to bring the level of virus back down to a level called a Viral Set Point, which is a relatively stable level of the virus. At this point, the CD4 count begins to increase, but it may not return to pre-infection levels.

Clinical Latency: After the acute stage of HIV infection, the disease moves into a stage called Clinical Latency. This period is also called Asymptomatic HIV Infection or Chronic HIV Infection. During this stage, HIV reproduces at very low levels, although it is still active. An undetectable viral load and a healthy CD4 cell count may be maintained during the earlier years of this phase. There may not be symptoms. This period can last up to 8 years or longer.

While some people progress through this phase faster than others, it is important to remember that HIV is still able to be transmitted to others during this phase.Toward the middle and end of this stage, the viral load will begin to rise and the CD4 cell count will begin to drop. When this happens, their may be constitutional symptoms of HIV (fever, night sweats, weight loss and fatigue) as the virus levels increase.

AIDS: If the number of CD4 cells falls below 200 cells per cubic millimeter of blood or an opportunistic infection is developed, a person is considered to have AIDS. A normal CD4 count is between 500 and 1,600 cells/mm3. This is the stage of infection that occurs when your immune system is badly damaged and you become vulnerable to opportunistic infections. At this stage, it is important to know that treatment is still absolutely possible yet extremely urgent.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Copyright 2018, Positive Health Publications, Inc.

This magazine is intended to enhance your relationship with your doctor - not replace it! Medical treatments and products should always be discussed with a licensed physician who has experience treating HIV and AIDS!