NSC2500 - HIV-AIDS: Pathophysiology, Management, and Zidovudine

This presentation provides a comprehensive overview of HIV-AIDS, starting with an introduction to the virus as a retroviral disease. It details the normal physiology of the immune system and how HIV disrupts it, focusing on the inactivation of Th cells (CD4+ cells) and the resulting immune deficiency. The presentation explains the process of viral replication, including the role of gp41 and gp120 proteins in infecting host cells. It then delves into the mechanism of action of antiretroviral therapy, specifically highlighting Zidovudine (AZT) as a reverse transcriptase inhibitor. The pharmacokinetics of Zidovudine are discussed, including its prodrug nature, intracellular activation, and metabolic pathways. The presentation also covers the mode of administration, side effects, contraindications, and precautions associated with Zidovudine. Finally, it explores non-pharmacological interventions, such as patient education and safe sex practices, to promote comprehensive HIV/AIDS prevention. The presentation concludes with a summary of key points and a list of references.

Presented By:
HIV-AIDS: A Retroviral Disease
and Management

Introduction
HIV/AIDS: Human
Immunodeficiency Virus: Acquired
Immunodeficiency Syndrome
Causative agent: Retrovirus (Punt
et al., 2019)
27,545 people resides in Australia
with HIV and 63% of this is
attributable due to sexual contact
between men (Australian
Federation of AIDS Organisations,
2017)
Other mode of transmission is
from mother (infected) to child

Normal physiology of Immune
System
(Source: Punt et al.,

Pathophysiology of the
Disease
AIDs virus carries their genetic information in the form of
RNA
As the virus enters the cell, RNA (2 copies) is reverse-
transcribed to c-DNA (provirus) by virally encoded enzyme
reverse transcriptase (RT) (p64)
Provirus is integrated into the host cell genome and is
replicated along with host's DNA (Th cells or CD4+ cells)
Replication leads to expression of new virons with the lyses
of the host cell
HIV-AIDS thus hamper the cell-mediated immune response
Inactivation of Th cells (CD4+) cells further hampers the
activation of humoral immune response: B-cell leading to
comprehensive loss of immunity (immunocompromised)
(Punt et al., 2019)

The process of viral replication
AIDs virus infect human T cell leading to cell lysis
Gp41 transmembrane protein of the virion gp 120
associated with gp41 acts as a viral receptor for
CD4+ Tcells of the host
Within the viral envelop is the nucleo-capsid that
contains p17 and an inner layer of protein called p24
Once the viral genome enters the cell, the two
copies of single stranded RNA is converted t DNA by
p64 (RT) and intregrase protein p32 helps in the
insertion of the viral genome inside the host genome
(Punt et al., 2019)

Cross-sectional schematic diagram of HIV virion
(Source: Punt et al., 2019)

Viral Infection Pathway
(Source: Punt et al., 2019)

The mechanism behind medication
management of HIV
The viral particles lyse the host cell
(CD4+ T cells)
The newly formed viral particles
further infects CD4+ T-cells leading
to complete destruction of the CD4+
T-cells and thereby generating
immune-deficiency
The role of anti-retro viral therapy is
to inhibit viral replication and thus
restricting the death of CD4+ T cells
and retaining immunity
(Source: Punt et al., 2019)

Drug target
(Source: Punt et al., 2019)

Selected drug: Zidovudine (Retrovir,
AZT)
Chemical structure of AZT

Mode of action of Zidovudine (ZDV)
Reverse transcriptase inhibitor: nucleoside
analog
DVZ TRP inhibits the activity of HIV-1 RT
DVZ competes with natural nucleotide
counter-part of thymidine triphosphate for
incorporation inside the newly synthesized
viral DNA molecule
Incorporated inside the DNA molecule chain
leads to chain termination of DNA synthesis:
cessation of viral replication
(Punt et al., 2019)

Pharmacokinetics: Zidovudine
(ZDV)
ZDV is a prodrug
Its enters the T-cell through passive diffusion or
through uptake receptors: Human T-lymphotropic
virus type 1 (HTLV-1)
Inside the cell its is transferred from apical to basal
compartment
In the basal compartment it is activated by
intracellular phosphorylation
Phosphorylation is done by three different
intracellular kinases
(Mazaleuskaya et al., 2015; Mu et al., 2016)