ABIM Exam Disease of the Week Profile: HIV/AIDS
It’s important during your Internal Medicine Board Review to understand the concept of pathophysiology, risk factors, and management of the Human Immunodeficiency Virus (HIV). HIV could go the way of smallpox and polio and be eliminated or eradicated in the decades to come. That’s the hope after a group of Danish scientists announced that they have fifteen patients taking part in trials on a promising, novel treatment.
We’ll get back to this potentially ground-breaking news, reported last week in the U.K’s Daily Telegraph. Let’s first review HIV, our featured ABIM Board Exam disease of the week:
HIV is an example of a retrovirus containing a single-stranded RNA genome. If left untreated, it can lead to Acquired Immune Deficiency Syndrome (AIDS).
HIV contains two copies of the positive single-stranded RNA that encodes for the virus’s nine genes. The nine genes are enclosed by a capsid (protective shell of the virus) known as p24 viral protein. There is another protein known as glycoprotein 120 (gp120) present on the surface of the virus that plays an important role in the attachment of the virus to specific CD4 host cells. When this binding occurs, gp120 undergoes a structural change that allows the chemokine binding domain of the molecule to become exposed. The chemokine binding domain of gp120 binds to chemokine receptors of the target CD4 cell (known as CXCR4 and CCR5 portion of the target cell). This binding of gp120 to the CD4 molecule of the target cell and the chemokine binding domain of gp120 to the chemokine receptors of the target cell allows for a stable two-pronged attachment. Once this attachment occurs, the virus can now enter the host cell.
Upon entering the human host, the enzyme reverse transcriptase converts the single-stranded RNA code into double-stranded DNA, which is then integrated into the host genome by the enzyme integrase. The hybrid of HIV and host DNA leads to the development of a provirus, which is transcribed into messenger RNA (mRNA). After exiting the nucleus, mRNA enters the cytoplasm of the target cell, where it is translated into viral protein. The enzyme protease cleaves the viral protein, leading to the replication of new viral particles that lyse the host cell and allow it to infect other host cells. The most common type of cell HIV destroys is the CD4 helper T cells. With depletion of CD4 helper T cells, cell mediated immunity is lost, which increases chances of opportunistic infections. Other cells that can get affected by this virus are macrophages, dendritic cells, and glial cells.
People at increased risk for developing HIV include: individuals having multiple sexual partners, men who have sex with other men, patients infected with hepatitis B or C, blood transfusion recipients (prior to 1985), and intravenous drug users.
The diagnosis of HIV is initially made by checking an enzyme-linked immunosorbent assay (ELISA) which detects antibodies to the virus. This is a screening test for HIV that yields a positive result by three months after an initial infection. Confirmatory test for HIV is a Western blot. Western blot is used to detect specific proteins from a specific tissue homogenate or extract. The proteins are separated by gel electrophoresis based on their length and transferred onto a membrane, where they are stained with specific antibodies.
The current goal of managing HIV is to prevent the depletion of CD4 cells (which protects cell mediated immunity and prevents opportunistic infections) and to make the viral load undetectable in the blood. The main classes of medications used in the management of HIV are: fusion/entry inhibitors, nucleoside and non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors. These classes of medications do not destroy the virus but help keep the virus undetected in the blood and “latent” within the host genome so that opportunistic infections do not occur. NBA Hall of Famer Earvin “Magic” Johnson is a perfect example of an individual who is living a normal, healthy life since being diagnosed with HIV in 1991.
The future of HIV is to find a permanent cure for the disease rather than managing it with daily medications. Currently, if medications are discontinued, the virus will no longer remain dormant in the host genome and quickly start replicating and initiate destruction of other cells.
The clinical trials reported above attempt to reactivate HIV from its “reservoirs” within the host DNA genome and expose the virus to the surface of the host cell where the body’s natural immune system may be able to destroy the virus. Panobinostat, which has also been used against various lymphomas, is the name of the potent drug being studied in the trials.
The challenge, however, lies in the strength of a specific individual’s immune system—the body’s ability to recognize the virus and destroy it. The first set of results from the Danish trial are expected in the second half of 2013. The world–including over 33 million people living with HIV/AIDS–will be closely watching.
You can see all the previous ABIM Exam disease of the week blog posts at the Knowmedge Blog. You can find also additional topics and questions directly from the Knowmedge Internal Medicine ABIM Board Exam Review Questions QVault.