HIV Life Cycle Left Untreated

HIV regimens can keep the virus at undetectable levels in your body. HIV specialists can vary somewhat in when you should start a regimen although the current Department of Health and Human Services Guidelines recommends that therapy should start regardless of a person's CD4 ("T-Cell") count. That basically means you should start therapy right away after diagnosis, in an effort to reduce the virus doing any damage to the body by progressing. It's important to keep in mind that some people are diagnosed with HIV well after (years after) they have been infected, for many different reasons.

When a treatment regimen has been started, adhering to it (taking medications on time, every time) is also very important to keeping HIV in check. With HIV, if you don't take the regimen as directed not only can it progress and begin to do damage to the body, the HIV can also become resistant to the regimen. There are alternative regimens and salvage regimens today but there are still only so many so adherence is key to not letting the virus progress and get out of control.

How Untreated HIV works:

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 Steps Of Untreated HIV:

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 three FDA approved Entry and Fusion Inhibitors - Selzentry and Fuzeon, neither of which are currently recommended in the DHHS guidelines for first time use and a new drug, Trogarzo which is awaiting DHHS status.

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 13-different NRTIs approved for use by the FDA, many however have become not recommended. The NRTIs which are currently considered recommended are – Descovy, which is a newer entry in this category. Emtriva and Viread (in combination to form Truvada) and Epivir and Ziagen (in combination to form Epzicom).

Five different NNRTIs are approved by the FDA. The “Recommended in Certain Clinical Situations” designated drugs in this category are Sustiva and Edurant (when used in combination to form the single tablet regimen, Complera.)

As noted, the drugs in these two categories are also co-formulated with drugs from other HIV-fighting categories in single tablet regimens such as Biktarvy, Genvoya, Atripla, Complera, Odefsey, Triumeq, Stribild and Juluca or combination pill regimens like Truvada and Epzicom.

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 and there are currently 3-approved by the FDA. Isentress, Vitekta and Tivicay are all recommended in DHHS guidelines.

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.

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 11 - drugs approved by the FDA in this category. Prezista/Prezcobix and Reyataz/Evotaz are currently listed as "Recommended In Certain Clinical Situations" in this category.

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.

How Untreated HIV Progresses

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 destroy 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.

If you have a lifestyle that is considered "At Risk" for contracting the HIV virus and are not currently HIV-positive, please get tested! The sooner you know your status, the much better off you are and you can stop HIV before it progresses in your body. If you are HIV-positive, please start treatment or adhere to your current regimen - It is vitally important!

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!