The Human Immunodeficiency Virus ( Hiv )

CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. HIV infects cells of the immune system called T lymphocytes (T cells) and macrophages. HIV has an envelope and contains two copies of single-stranded RNA as the genome. Within the viral capsid are important viral enzymes called reverse transcriptase, integrase, and protease. The HIV virus has a spike protein that is called gp120, and the host cell receptor is CD4+. HIV belongs to a class of viruses called retroviruses. Retroviruses are RNA viruses, and to replicate or reproduce, they must make a DNA copy of their RNA through transcription and translation. It is the DNA genes that allow the

As have been described above, HIV can have a potential effect on immunological cells, which are important to protect the body from additional infections such as Tuberculosis (TB), Cytomegalovirus (CMV) and other viral or bacterial infections. An effective treatment is needed to reconstruct what HIV has damaged. Antiretroviral therapy (ART) is a common treatment to stop the viral replication and decrease the disease progression, which may lead to a vast decline of the morbidity and mortality. The standard treatment involves a combination of at least three drugs; often known as a highly active antiretroviral therapy (HAART) where the most common types are Nucleoside reverse transcriptase

Pharmacologic treatment for HIV-infected patients consists of antiretroviral (ARV) medications which cover six classes of drugs including nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PT), a fusion inhibitor (FI), a CCR5 antagonist, and integrase

The HIV life cycle occurs in six stages namely; Fusion, Reverse transcription, Integration, transcription, assembly, and budding. Inorder for the virus to proceed to each stage and continue to replicate into new viral cells, it requires catalytic enzymes such as reverse transcriptase (RT), Intergrase (IG), and protease (PT). These replicating enzymes and cycle phases have been identified as potential therapeutic drug targets for HIV-therapy (Fig 2), therefore leading to the development of novel anti-retroviral drugs as stated below;

HIV has been a life destroying disease since the early 1980s. Originally discovered in gay men, it was once thought to only effect homosexuals. Thankfully to great efforts on research and outbreaks in hemophiliacs, it is now associated with other social groups outside of the gay community. The risks of contracting this disease are still high among gay men, highly sexually active individuals (hetero-, homo-, and bi- sexual), intravenous drug users, and health care professionals. By understanding the biological make up of the disease researchers have been able to come up with many options to treating the disease, its progression into AIDs, and other infections that can occur

Over the last three decades, the Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Disease (AIDS) epidemic has been a public health concern in the United States (US) and globally. Centers for Disease Control and Prevention [CDC], (2015d) estimates that in the US, over 1.2 million people are living with HIV, of which 12.8% are unaware of their diagnosis. Due to exceptional medical advances in treatment and prevention strategies, a healthier quality of life and longevity can now be achieved with persons diagnosed with HIV (Irvine et al., 2014; CDC 2015a; Sayles, Wong, Kinsler, Martins, & Cunningham, 2009). However, despite the advance from a deathly diagnosis to a chronic disease, the continuum of care in treatment is still threatened.

Currently, 1.2 million people in the United States have been diagnosed with HIV, or human immunodeficiency virus, with the number of new HIV diagnoses declining by 19% from 2005 to 2014 (aids.gov). This decrease in diagnoses is due to the new medical advancements and scientific findings, specifically the discovery of nonprogessers, broadly neutralizing antibodies (bNAbs), and how these bNAbs can offer a new insight on HIV treatment and prevention.

The ability of the virus to choose its co-receptor is called viral tropism and determines its virulence and disease progression rate. If the virus binds with the co-receptor CCR5 it is called macrophage-tropic (M-tropic) and characterizes most HIV infections. The M-tropic variant is regarded as less virulent because it is nonsyncytial. Some mutations of the CCR5 gene lead to a partial immunity to the virus and can slow the disease and in some cases prevent infection of the M-tropic HIV varient. Also patients with high levels of CCR5 soluble chemokines are more resistant to the virus.

Due to how HIV replicates with reverse transcriptase, many errors result during replication of the genome. The diversity of the HIV genome can cause difficulties when developing a HIV vaccine. Dr. Not A Scientist indicated problems resulting from the body’s inability to develop antibodies during natural HIV infection. This inability would also mean that an HIV vaccine wouldn’t be able to produce HIV-specific antibodies. However, Dr. Not A Scientist is incorrect because HIV-specific antibodies develop within approximately 1 week of infection. Still one problem arises from the high mutation rate: the ability of antibodies to bind to HIV antigens. Antibodies are antigen specific and fit like a lock and key. When the HIV genome makes errors during replication on mutates, surface proteins can change causing HIV-specific antibodies to no longer be able to bind [5].

HIV primarily targets components of the human immune system that express the CD4 protein as a surface receptor, such as CD4+ T cells, which are mature T helper cells that express the protein on their surface, macrophages, and dendritic cells. HIV gains entry into these cells through interaction of the virion’s gp120 protein with the CD4 receptor molecule on the target and also, secondarily, with chemokine co-receptors, including CCR5 and CXCR4.

The disease HIV, also known as human immunodeficiency virus, is a virus that is transmitted through bodily fluids that cause an attack on the body’s immune system and destroys T cells, which help defend the immune system from infectious diseases (CDC, 2015 A). HIV is a prevalent public health issue because it is a preventable disease, but over 1.2 million Americans are living with the disease and the numbers keep increasing yearly (CDC, 2011 A). Also, 1 out of every 5 American living with HIV are unaware that they have the disease (CDC, 2011 B). Studies show that in 2014 there were around 51,000 new cases of HIV diagnosis (CDC, 2011 B) Adult and adolescent males from the ages of 13 and 24 years old make up 81% of all the HIV cases (CDC, 2014). The main targeted groups for HIV are, 1 in 6 gay/bisexual men, 1 in 20 African American men, 1 in 48

HIV is Inevitable. It’s hard to believe that it has been 35 years since the first appearance of HIV in the US. It has claimed millions upon millions of people thus far. There is still a staggering number of people out there that are infected with this crippling disease. Everyone wants, wish, or even dream of a Cure, but a Vaccine could be a within reach in the near future. Through Money, Research and Development, we are sure to see a big changed in HIV by 2030. Predicted by Bills Gates (Business Insiders 2015). Understanding what we’ve learn from our past, and new ways on the developmental path for a vaccine; could be a game changer for a possible Vaccine for HIV yet to come. With our current statistic in front of us, we need to Act Now! This Movement & Progression for a vaccine could be a true reality.

HIV follows specific steps in order to infect the host. In the first step of the HIV life cycle, binding occurs. In this step, HIV attaches itself to a specific white blood cell known as CD4.1 These cells are responsible for sending signals to activate the immune system response in helping detect harmful pathogens.2 Fusion of the HIV and CD4 envelope then allows HIV to enter the CD4 cell.1 Once in the cell, reverse transcriptase is released in order to convert HIV RNA into HIV DNA.1 Because of that, HIV is now able to enter the CD4 nucleus. HIV then uses another enzyme integrase which allows HIV DNA to combine with CD4 DNA.1 Soon after, HIV proteins are made from the machinery of CD4; those proteins are the blueprints in making more HIV.1 The new HIV proteins and RNA assemble into new immature HIV once in the surface of the cell.1The last step is budding, in this step the new HIV goes outside of

Human Immunodeficiency Virus: Development of the C-C Chemokine Receptor 5 (CCR5) Antagonists as an Effective Treatment.

The final outcome of the HIV infection is the Acquired Immune Deficiency Syndrome (AIDS) (Dennis H Osmond; Susan Buchbinder; Amber Cheng; Allison Graves) (2002). There are two subtypes of the virus, HIV-1 and HIV-2. They both originate from the Simian Immunodeficiency Virus (SIV) which was found in Africa. The source of the HIV-1 virus was in chimpanzees coming from central Africa. The source of HIV-2 virus was from west Africa derived from Soot Mangabey Monkeys (Rambout et al., 2001). HIV belongs to a family of viruses known as lentiviruses. Paul M. Sharp and Beatrice H. Hahn (2011) explain in their article that lentiviruses are viruses that slowly act over a long period of