HIV/AIDS

Question 1

What is the HIV replication cycle?

Answer 1

1. Fusion of HIV to host cell
   2.HIV RNA, reverse transcriptase and other viral proteins enter host
2. Viral RNA > viral DNA by reverse transcription
3. Viral DNA transported across nucleus- integrates into host DNA
4. New viral RNA used as genomic RNA and to make viral proteins
5. New viral RNA and proteins move to cell surface, new IMMATURE HIV forms
6. Virus released. Viral protease cleaves new poly proteins- MATURE INFECTIOUS VIRUS

Question 2

What is the WHO classification of HIV/AIDS stages?

Answer 2

Stage 1: asymptomatic, CD4+ count> 500/uL
Stage 2: mild symptoms, CD4+ count <500uL
Stage 3: advanced symptoms, CD4+ count <350/uL
Stage 4/AIDS: severe symptoms, CD4+ count <200/uL

Question 3

What is ART and what is the purpose of combining it?

Answer 3

Antiretroviral therapy
Combination- enhance efficacy of single agent
Minimise chance of toxicity by minimising individual doses
Prevent or delay resistance

Question 4

What types of guidelines does the BHIVA provide?

Answer 4

*initiation of treatment- what drugs and when
*viral load detection and genotypic resistance testing
*switching therapy- when viral load becomes detectable ie >200 HIV RNA copies/mL
*salvage therapy- for patients who failed at least 2 antiretroviral regimens

Question 5

What is the primary aim of ART?

Answer 5

*HIV RNA copies <50 copies/mL
*thus reducing HIV mortality and morbidity
*with low level of drug toxicity
*reduce transmission
*improve physical and psychological well being of infected

Question 6

When should ART be started?

Answer 6

*asap- even CD4+ lymphocytes count over 500 cells/uL
*lifelong- don’t stop. Viral rebound for those who stop
*neurological involvement
*any sign of AIDS
*PHI within 12 weeks of a previous negative test

Question 7

What is the initial treatment plan for HIV?

Answer 7

*one integrase inhibitor + one or two nucleoside RT inhibs
Alternative if viral load >200 copies/mL
*one protease inhibitor/NNRTI/ integrase inhib with a BOOSTER + 2 NRTI

Question 8

What is a nucleoside RT inhibitor?

Answer 8

*competitive substrate to RT- act like it
*incorporated into proviral DNA
*DNA malformed- cannot integrate

Question 9

What is a non nucleoside RT inhibitor?

Answer 9

*bind to hydrophilic pocket in RT
*alters active is altered
*inactivated enzyme
-Doravirine

Question 10

What is an example of a booster?

Answer 10

Ritonavir (Both a PI and booster)

Question 11

Which inhibitor group has greater tolerability and less drug drug interactions?

Answer 11

Integrase inhibitors

Question 12

How does an attachment inhibitor work?

Answer 12

example- fostemsavir
Binds to viral gp120- blocks viral attachment to CD4+ T cells