HIV And The Acquisition Of The Development Of R4 Tropic HIV

There are four main groups of HIV strains (M, N O and P), each with a slightly different genetic make-up. This supports the hunter theory because every time SIV passed from a chimpanzee to a human, it would have developed in a slightly different way within the human body, and produced a slightly different strain. This explains why there is more than one strain of HIV-1 The most studied strain of HIV is HIV-1 Group M, which is the strain that has spread throughout the world and is responsible for the vast majority of HIV infections today. (“origin of HIV & AIDS,”

(2011) was a multi-continent, randomized, controlled trial to evaluate the effectiveness of antiretroviral therapy on the speed of the disease process among HIV-1 infected and HIV-1 uninfected partners. In the study, 1,763 HIV mixed status couples were grouped into either early antiretroviral and delayed therapy groups. Inclusion criteria consisted of the HIV-1 infected participant having a CD4 count between 350 and 550 with no previous antiretroviral therapy usage, except to prevent mother-baby transmission. Participants attended three monthly sessions and then quarterly sessions until ill or requiring an additional amount of antiretroviral drugs (Cohen et al, 2011). The uninfected partners were tested each quarter for seroconversion, the period in time in which antibodies become detectable. The research study concluded that early antiretroviral therapy initiation had a greater effect on CD4 count than delayed antiretroviral therapy. The average CD4 count in the early therapy group originated at 400 and increased to 603 after 12 months of ART. A decline of CD4 cells were noted in the delayed group (Cohen et al, 2011). The authors concluded that a higher incidence of HIV transmission was noted in African countries and adverse effects were more likely to occur in the early therapy group. Early therapy had a positive effect on the HIV-1 uninfected and HIV-1 infected

b. HIV is an incurable disease that relies on coreceptors to initiate host cell interaction and proliferates by utilizing the host cell’s own machinery to reproduce new virus. We will more deeply explore the mechanism in which HIV virions infiltrate and deceive our host cell. In addition, we will discuss current treatment and research that are in the process of finding a highly coveted cure.

Recent studies suggested that CD4 domain specific monoclonal antibody such as mAb (15A7) and Ibalizumab have a great revolution in HIV-1 treatment area. The majority of previous mentioned treatments constitute to either restore the immune response or decline the plasma vireamia, however, this type of treatment is more likely to interfere with the HIV-1 structure. Before explaining how this category of drugs works, it is necessary to clarify the reaction between HIV-1 glycoproteins and CD4. Once the virus enters the body, HIV-1 envelope glycoprotein (gp120) attaches to a cellular CD4 receptor. As CD4/gp120 is formed, it allows gp120 to attache to chemokine receptor-5 (CCR5) or CX chemokine receptor-4 (CXCR4) allowing gp41, another viral envelope molecule, to insert into the target cell membrane leading to fusion the viral envelope and cellular membrane (Christopher et al., 2010). Ibalizumab is CD4 domain-2 monoclonal antibody using as an effective treatment to enhance the CD4 counts. In a study which set out to determine the antiviral efficacy of Ibalizumab on HIV-1 positive patients not on (ART), (Christopher et al., 2010) found that the CD4 counts increase after one day of drug initiation even before the viral load decline. This suggested that the rise of CD4 counts is possibly due to redistribution of CD4 cells from lymphoid tissues rather than regeneration of these cells. Notably, niegher

Anti-genetic drift is a mechanism for different viruses that involve the accrual of mutations within genes that code for antibody bonding sites.

The CCR5 gene codes for a protein found on the surface of white blood cells that acts as a receptor for chemokines. The HIV virus, strain R5-tropic virus, initially uses the CCR5 chemokine receptor to attach to the CD4+ helper T-cells. The Berlin patient showed how a CCR5-negative hematopoietic stem/ progenitor cells (HSC) from a CCR5 ∆ 32 donor can be used to generate HIV-1 resistant CD4+ helper T-cells.3 Mice models using in vivo studies have also shown ZFNs to be very effective in creating this CCR5 ∆ 32 mutation and ultimately suppressing the HIV-1 replication. Holt and collegues3 performed a study using a mice model to demonstrate the use of ZFN-modified autologous HSC as a clinical approach to treat

Since the arrival of triple therapy, the challenge of sustained and complete viral suppression has been solved for the majority of patients [1]. The major limiting factors for improving the long-term success of ART are tolerability and convenient pill burden [2]. The latest class of the antiretroviral drug developed are Integrase inhibitors (INI). Dolutegravir (DTG) is an Integrase inhibitor, particularly focused on maintaining a favorable safety profile and a high efficiency rate, within a single-tablet regime (STR), it improves resistance barrier and allowing co-formulation with an NRTI backbone. Dolutegravir has been compared against both other classes of HIV anti-retrovirals as well as other integrase nuclear strand inhibitors. In August 2013, DTG was approved by FDA for its use in both patients who have never taken ART (ART-naïve) and patients who have taken ART (ART-experienced) [3]. It is predicted that very soon a STR containing Dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) will become

recognize a protein that is present on the surface of all HIV strains and neutralize the effects of the

Riviere, L., Darlix, J., & Cimarelli, A. (2009). Analysis Of The Viral Elements Required In The Nuclear Import Of HIV-1 DNA. Journal of Virology, 729-739. Retrieved October 4, 2014.

HIV has evolved in new varieties over the last dozen years. The virus is constantly changing due to natural selection and the environment of the patient's body. Inside the body, HIV replicates and every time it reproduces, random genetic copying mistakes mutations result in slightly different varieties of the virus going into the bloodstream. Some of these varieties will have traits that will make them resistant to certain drugs. Natural selection favors the drug resistant forms, causing them to survive and reproduce while causing medication to not work. It was discovered in 1970, that a patient suffering with HIV whose medication did not work, by going off the drugs made his virus population soon change from being resistant to every drug to then being susceptible. This was caused by the environment change in the body when stopping the medication. The non-resistant wild-type came back and started to replicate and soon outnumbered the drug-resistant strains. This resulted in a new treatment used today. If you take a patient that is resistant to medication, off the drugs for a certain amount of time and the virus reverts to the non-resistance wild-type, then hit it hard with a combination of drugs.

HIV RNA (viral load) and CD4 T lymphocyte (CD4) cell count are the two surrogate markers of antiretroviral treatment (ART) responses and HIV disease progression that are used to manage and monitor HIV infection. The key goal of ART is to achieve and maintain durable viral suppression. If a patient has virologic failure, it means that they are unable to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL. Therefore, they should be assessed for virologic failure which include an assessment of adherence, drug-drug or drug-food interactions, drug tolerability, HIV RNA and CD4 T lymphocyte (CD4) cell count trends over time, treatment history, and prior and current drug-resistance testing results. Moreso, drug-resistance testing should be performed while the patient is taking the failing antiretroviral (ARV) regimen or within 4 weeks of treatment discontinuation.

The protein is like most GPCR receptors in that it contains seven transmembrane domains (7TM), three extracellular loops (ECL1-ECL3), three intracellular loops (ICL1-ICL3), an amino terminal located outside the cell and a carboxy tail situated in the cytoplasm (Figure 3). Disulfide linkages between cysteine residues on the N-terminus and extracellular loops stabilize the conformation of the protein. Several posttranslational modifications in the CCR5 protein are essential for chemokine and HIV-1 binding. Specifically, CCR5 contains sulfated Tyrosine’s and acidic residues on the N-terminus that assist in gp120 attachment. The amino terminal and the largest extracellular loop, ECL2, of the CCR5 co-receptor permit R5 HIV binding (Barmania and Pepper 2013).

HIV has two major types: HIV-1 and HIV-2. HIV-1 has four groups M, N, O and P. These groups are further classified into subtypes. Group M is a major infecting group worldwide contributing to 90% of HIV-1 infections. Group M is classified into nine subtypes (A, B, C, D, E, F, G, H, J and K). Subtype B is predominantly found in America and Western Europe. The susceptibility to HIV-1 infection, transmission of disease, and response to retroviral therapy depend on the genetic determinants of the host cell. These genetic determinants vary in populations and among patients. These genetic variants regulate chemokine co-receptors and ligands that involve in the entry of the virus, major histocompatibility complex, killer cells Ig like receptor and cytokines, and TRIM5α motif and apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (Kaur and Mehra, 2009). In genome-wide association studies performed in European population, it was shown that Human leukocyte antigen (HLA) class I variation (Eg. HLA-B*5701) is the major contributor to viral set point and CD4+ T cell decline (Fellay et al., 2010). Cohort study of genetic polymorphism in chemokine receptors in Indian population has shown that protective CCR5 Δ32 variant is rare and CCR5HHE carrying *59402A has the high likelihood of infections (Kaur and Mehra, 2009). HIV Sequence Database contains annotated HIV sequences

In the early 2020’s an oral medication was developed to treat HIV/AIDS, eventually this medication came to be the new ‘cure’ for the infection. In the following years, HIV was no longer an issue or a cause for concern, as health professionals declared an HIV/AIDS free world. Nine years later, in 2031 a new strain of HIV emerged. This new strain has become resistant to the original oral medication that ‘cured’ HIV/AIDS years before. In addition, the virus has mutated to a point in which that it is spreading at twice the pace as the original strain. The virus is more aggressive and no course of previous treatment has proved effective in mitigating the effects. Thus, individuals have come under greater risk of being infected

HIV becomes drug resistance when the ARV treatments’ are not adhered to. Once the patient has taken their antiretroviral (ARVs) medication then stops the HIV is able to replicate and will do so at a rapid rate. As a result mutations are very common (Jen Gorgan and Ruth Suter;2009)