2016/2017- Essay 1

Question 1

Title

Describe the** mode of action** of antiretroviral drugs and the mechanisms by which HIV can develop resistance.

Answer 1

Modeo of Action of Antiviral Drugs and Mechanisms of HIV Resistance

Question 2

Introduction

Answer 2

• Human immunodeficiency virus (HIV)
• > causative agent for aquired immunodeficiency syndrome (AIDS): severly weakens immune system
• vulnerable to infections, cancers
• Emegence of HIV/AIDS-> research to develop effective treatments
• Antiretroviral drugs (ARVs)
• > managing HIV infection
• > improve quality of life

Explore mode of action of ARVs
Mechanisms HIV resistance to ARVs

Question 3

Mode of Actions of ARVs

Paragraph 1

Answer 3

• ARVs inhibit diff stages of HIV life cycle
• Target key enzyme and proteins involved in replication process
• Prevent viral replication and load in to body

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTs)
* Resemble DNA, incooperated into viral DNA by reverse transcriptase enzyme
* Leads to production of faulty DNA chains
* Halt elongation of viral DNA strand
* Effective inhibit viral replication

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
* Bind directly to reverse transcriptase enzyme at a different site than NTRIs
* Cause conformation change, renders enzyme inactive
* Reverse transcription disrupted
* Prevent viral DNA forming

Protease inhibitors (PIs)
* Inhibit protease enzyme
* >respible cleaving newlt synthesised viral proteins into function forms
* Improper protein cleavage-> immature and non-infectious virions
* Hinder maturation of new virus

Integrase inhibitors (INSTIs)
* Block integrase enzyme
* >role integrating viral DNA into host cells genome
* Viral cannot be integrated, prevent viral replication

Entry inhibitors
* Target initial stages of viral infection
* How: block viral fusion with host cell membrane/prevent virus attaching to specific receptors on cell surface
* 2 subtypes
* >Fusion inhibitors
* CCR5 antagonists

Question 4

Mechanism of HIV Resistance

Paragrah 2

Answer 4

• HIV: high genetic variability and rapid replication rate
• Develop resistance to ARVs drugs
• > ineffective in controlling infection
• Several mechanism, development of HIV resistance

Mutation
* HIV has high mutation rate
* Due to error prone nature of reverse transcriptase enzyme
* Random mutations during viral replication
* >changes in viral proteins targets by ARVs
* Resistance - allow virus to replicate despite treatment

Selective pressure
* ARVs exert selective pressie
* Favour survival and replication of drug-resistant variants
* Pateint taking ARVs: drug sensitive virus suppressed, drug resistant strain have selective growth advantage
* Overtime, resistant strains dominant viral population

Cross-resistance
* Some mutation lead to cross resistance
* >single mutation resistant to multiple drugs within the same class
* Limitation to treatment options for patient witg multi-drug resistant HIV

Combination of mutations
* Resistance due to accumulation of multiple mutations in different regions of its genetic code
* lead to more robust resistance profile

Question 5

Conclusion

Answer 5

• ARVs revolutionised management management of HIV/AIDs
• Extending lifespan and improving quality of life

Understanding mode of action
* Developing effective treatment strategies
* Challenge: HIV resistance
* Monitor HIV patients closely- employ combination therapy
* continue develop new drugs of ever evolving HIV virus
* Ongoing research, advancements in medical science strive better control of HIV/AIDS to find a cure
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