AW L1 HIV

Question 1

HIV infection has slowed recently due to….

Answer 1

policy, knowledge, reducing risk factors.

Not drugs.

Question 2

HIV primarily infects …………. cells

Answer 2

CD4+ T cells

Question 3

What receptor on the HIV binds first?

Answer 3

GP 120

Question 4

Coreceptors on HIV… (2)

Answer 4

CCR-5
CXCR4
(usually uses one or the other)

Question 5

Co receptor binding causes a conformational change in order to….

Answer 5

bring GP41 closer to the surface - binding the membrane fusion - single stranded RNA from virus enters

Question 6

HIV is super smart becuase

Answer 6

it uses the host cell machinery to replicate its DNA

Question 7

HIV is characterised by …….

Answer 7

chronic immune system activation leading to dysfunction

Question 8

HIV results in increased expression of ………. on ……. and …… cells

Answer 8

CD38 on CD4 and CD8 cells

also increased T cell proliferation

Question 9

What is the best correlation for progression of the disease….

Answer 9

levels of CD38 expression on CD4 and CD8 cells

Question 10

Despite immune deficiency virtually all components of the immune system show activation, including (4)

Answer 10

B cells
NK cells
T cells
macrophages

Question 11

Mutation in europeans means….

it inactivates….

Answer 11

resistance as the particle cannot enter the T cells.
inactivates CCR-5
(related to primary spread of the virus rather than enhanced immune response)

Question 12

CD4 and CD8 expression is ……………. in HIV

Answer 12

elevated

Question 13

Increased levels of pro inflam cytokines such as ………….. in HIV

Answer 13

IFN-a, TNF-a, IL6

Question 14

Elevated CD4 T cells but CD4 t cells depletion, why?

Answer 14

only infected T cells stimulated to proliferate - defective as viral DNA has been introduced

Question 15

Opportunistic infections in HIV e.g. (5)

Answer 15

Candida
Cytomegalovirus
Herpes simplex
TB
Mycobacterium avium complex

Question 16

What used to be the most common cause of death amongst AIDs patients

Answer 16

TB

- increases the likelihood that infection with m. tuberculosis will lead to TB disease

Question 17

How does the presence of TB affect the HIV infection

Answer 17

allows more rapid progression of the HIV

Question 18

Most HIV drugs have been developped against what target?

Answer 18

reverse transcriptase and protease (AZT)

Question 19

Virus undergoes mutations which is a problem with treatment becuase

Answer 19

develops resistance

Question 20

Why treat in combination….

Answer 20

treatment with a single drug tends to select mutant strains

Question 21

5 classes of HIV drugs

Answer 21

1. NRITIs
2. NNRTIs
3. Protease inhibitors
4. Entry/fusion inhibitors
5. Integrase inhibitors

Question 22

Gerneally HARRT treatment involves …………… different antiretrovirals from at least ………… classes

Answer 22

3 different drugs

2 classes

Question 23

HAART stands for

Answer 23

Highly active antiretroviral therapy

Question 24

NRTI stands for

Answer 24

nucleoside reverse transcriptase inhibitors

Question 25

NRTIs mode of action

Answer 25

act as chain terminators or inhibitors at the substrate binding site of reverse transcriptase

Question 26

NNRTIs stands for

Answer 26

Non-nucleoside reverse transcriptase inhibitors

Question 27

NNTRIs mode of action

Answer 27

bind to allosteric non-bonding site of reverse transcriptase, causing conformational change in active site - inhibit viral DNA replication

Question 28

Protease inhibitors mode of action:

Answer 28

non-scissible substrate analogue for HIV protease | Protein does not get chopped up so the new virus is not viable

Question 29

during reproductive cycle of HIV a specific protease is needed to

Answer 29

process GAG and POL polyproteins into mature HIC components

Question 30

PI contain a .......... bond instead of a .......... bond

Answer 30

hydroxyethylene bond instead of a peptide bond

Question 31

Fusion inhibitor e.g.

Answer 31

fuzeon (36 amino acid peptide produced synthetically)

Question 32

Fuzeon mode of action

Answer 32

blocks entry of HIV into cells (CD4 or T cells)

Question 33

Fuzeon works by mimicking....

Answer 33

components of GP41

Question 34

Why is fuzeon super-dooper awesome?

Answer 34

Targets the virus so less toxic & prevents infection in the first place

Question 35

Entry inhibitors e.g.

Answer 35

Maraviroc

Question 36

Maraviroc inhibits ..... | mode of action....

Answer 36

CCR5 | Blocks HIV attachment to CCR5, halting HIV replication.

Question 37

Maraviroc is only effective against....

Answer 37

HIV that uses the CCR5 receptor site (HIV using CXCR4 is unaffected)

Question 38

The process of HIV using host cells' genetic material to makes its own DNA is called....

Answer 38

reverse transcription

Question 39

Integrase enzyme has what function

Answer 39

integration of genetic material into the genetic material of the host cell

Question 40

Mode of action of integrase inhibitors

Answer 40

Block integrase, preventing the virus from adding its DNA to the host DNA in CD4 cells - prevents replication and making new viruses

Question 41

e.g. of integrase inhibitor

Answer 41

Raltegravir

Question 42

What are fixed dose combinations?

Answer 42

Combination of 2 or more medications from one or more different classes - one pill

Question 43

HARRT is just a way of using the same drugs more effectively, does it alter progression or mortality?

Answer 43

Fewer mortalities | No change in progression

Question 44

4 Challenges to HAART therapy

Answer 44

Intolerance and long term tox Lack of adherence Co-morbidities Increasing drug resistance

Question 45

Barriers to adherance

Answer 45

- frequency and severity of ADR - conflict with daily routine - dietary requirements - frequency of medications - number and dosage of medications - psychosocial factors - pharmacy refills - physiological needs

Question 46

Major cause of mortality (4)

Answer 46

Liver disease (related to hepatotropic viruses) CV complications Renal disease Non-HIV related malignancies

Question 47

Future of HAART:

Answer 47

- improve current drug tolerability & convenience - preserve hepatic function - overcome resistance