HIV - Virology and Treatment

Question 1

Virology of HIV:

Initial infection and HIV replication cycle
HIV enters the body (e.g., via mucosal
lesions or via infection of mucosal
/cutaneous immune cells:

(1) What 3 cells does the HIV virus target?
(2) Then attaches to the CD4 receptor on target cells with its gp120
(3) Viral envelope fuses with host cell and capsid enters the cell - What coreceptor needs to be present for this to happen?
(4) What happens after this?
(5) Viral DNA is replicated and virions are assembled - what enzyme is involved in this process?
(6) Leads to production of more HIV virions (RNA) - may create different strains and it also leads to cell death

Answer 1

Cells with the CD4 receptor - T helper cells, dendritic cells and macrophages (also monocytes)

Macrophages involved in later stages of disease.

CCR5 in T cells and macrophages - can be CXCR4 in T cells - so people withOUT CCR5 receptors are resistant.

Individuals without CCR5 receptors appear to be resistant to HIV, those patients either have a homozygous (same gene on both alleles) CCR5 mutation (substantial resistance) or a heterozygous (different gene on alleles) CCR5 mutation (slower course).

CCR5 produced but at a slower rate! in heterozygous.

A virion’s RNA is transcribed into dsDNA by viral REVERSE TRANSCRIPTASE
Integrated into hosts DNA via integrase

Protease

Question 2

ACUTE HIV (Retroviral) SYNDROME:

• Why do they get persistent generalised lymphadenopathy?
• How would you know it could possibly be HIV with this initial presentation?

Clinical latency - how long does this tend to be?

Progression to chronic immunodeficiency:

(1) During the clinical latency phase, the virus mainly replicates inside the lymph nodes.
(2) How does this lead to immunodeficiency?

Increased viral load generally leads to a decreased number of CD4+ lymphocytes and vice versa, but the relation is not linear.

Answer 2

HIV infects CD4+ lymphocytes
Reproduces and spreads to others
CD4 lymphocytes concentrate at lymphoid tissue (hence lymph nodes) - hence ACUTE HIV SYNDROME

There is a high viral load - high amount of HIV in the blood

8-10 yrs

Time between infection and detectability of HIV antibodies

Increasing loss of CD4+ lymphocytes (especially T cells) impairs immune function and, thereby, facilitates opportunistic infections and development of malignancies (AIDS).

Question 3

Knowing the virology/pathophysiology of HIV., what are the 6 targets for drug treatment?

Answer 3

CCR5 antagonist - CCR5 need for HIV to bind to CD4 cells

Fusion inhibitors - inhibits HIV entering cells

Reverse transcriptase inhibitors (Nucleoside Reverse Transcriptase Inhibitors)

Intergrase inhibitors

Protease inhibitors

Question 4

Drugs for HIV:

CCR5 antagonist - CCR5 need for HIV to bind to CD4 cells

Fusion inhibitors - inhibits HIV entering cells

Reverse transcriptase inhibitors (Nucleoside Reverse Transcriptase Inhibitors)

Intergrase inhibitors

Protease inhibitors

Which type is always used?

Answer 4

Reverse transcriptase inhibitors (Nucleoside Reverse Transcriptase Inhibitors) - NRTI’s

Usually used as a triple therapy or NRTI + another drug

Just the basic principles: long term treatment, importance of combination therapy and adherence to prevent viral resistance, potential for drug-drug interactions.