HIV

Question 1

Epidemiology of HIV

Answer 1

RNA retrovirus which targets CD4+ T helper cells as hosts (also CD4+ monocytes and dendritic cells)
CD4 molecule is receptor for HIV. the virus binds via gp120 (initial) and gp41 (conformational change)
Most strains also use CCR5 and CXCR4 chemokine co-receptors

Question 2

How is HIV transmitted?

Answer 2

Sexual, infected blood, Mother-to-child (vertical- Breastfeeding, in utero, intra partum)

Question 3

what type of CD is involved in HIV?

Answer 3

CD4

Question 4

What glycoproteins does the virus bind to?

Answer 4

120 (initially)

41 (conformational change)

Question 5

Pathogenesis of HIV - The Innate Response

Answer 5

Non specific activation of macrophages, NK cells and complement
Stimulation of dendritic cells via Toll Like Receptors
Release of cytokines and chemokines

Question 6

Pathogenesis of HIV - The Adaptive Response

Answer 6

Neutralising antibodies - anti gp120 and anti gp41
Non-neutralising antibodies - anti p24 gag IgG
CD8+ T cells can precent HIV entry by producing chemokines MIP-1a, MIP-1b and RANTES which block co-receptors

Question 7

HIV damages the immune response

long card with loads of info on, if anyone can think how to split this into more cards please feel free

Answer 7

HIV remains infectious even when Ab coated
Activated infected CD4 helper T cells are killed by CD8 T cells
Activated infected CD4 helper T cells are energised (disabled)
CD4 T cell memory lost & failure to activate memory CTL
Monocytes and dendritic cells are therefore not activated by the CD4 T cells and cannot prime naive CD8 CTL (due to impaired antigen presenting functions)
Infected monocytes and dendritic cells are killed by virus or CTL
Quasispecies are produced due to error-rpone reverse transcriptase= these escape from immune response

Question 8

7 stages of the life cycle of the HIV virus

Answer 8

1) attachment/entry
2) Reverse transcription & DNA synthesis
3) Integration
4) Viral transcription
5) Viral protein synthesis
6) Assembly of virus & release of virus
7) Maturation

Question 9

What is the median time from infection with HIV to AIDS

Answer 9

8-10 years

Question 10

How many years is classed as rapid HIV->AIDS progressions?

Answer 10

2-3 years and happens in 10%

Question 11

What is Long Term no progression HIV and roughly what percentage of HIV pts have it?

Answer 11

stable CD4 counts and no symptoms after 10 years, occurs in less than 5% of pts

Question 12

What is a good predictor of disease progression?

Answer 12

Initial viral burden (set point)

Question 13

Screening test for HIV- what does it detect and what method is used?

Answer 13

Detects andi-HIV Ab via ELISA

Question 14

Confirmation test - what does it detect and what method is used?

Answer 14

Detects Abs via Western Blot. A positive test requires a pt to have seroconverted (started to produce Ab)

Question 15

How long after becoming infected will the pt have seroconverted?

Answer 15

after ~10 weeks incubation period

Question 16

After Diagnosis, what tests are carried out? what doe they detect and how are they done?

Answer 16

Viral Load - PCR is used to detect viral RNA
CD4 Count - via FACS (flow cytometry), used to assess course of disease, onset go AIDS correlates with diminution in number of CD4 T cells.

Question 17

Starting treatment and what guidelines are followed?

Answer 17

BHIVA Guidelines

if CD4 count

Question 18

What is HAART?

Answer 18

Highly Active Anti Retroviral Therapy = 2NRTIs + PI or NNRTI

example regiment - Emtricitabine + Tenofovir + Efavirenz - available as one pill Atripla

Question 19

HIV treatment during Pregnancy

Answer 19

Zidovudine

given Orally but switched to IV for delivery.

given to newborn for 6/52

Question 20

what are the limitations of HAART?

Answer 20

It doesnt eradicate latent HIV-1; fails to restore HIV-specific T-cell responses; toxicities; high pill burden;adherence; threat of drug resistance; QoL; cost

Question 21

HIV Treatment - what are the sites of action of the major drug classes?

Answer 21

1) Prevention of protein cleavage
2) block integration of the virus into DNA
3) block reverse transcriptase mediated trascription
4) block the docking process

Question 22

HIV Treatment - Protease Inhibitors - drug names? side effects?

Answer 22

Indinavir, Nelfinavir, Ritonavir, Amprenavir, Fosamprenavir, Lopinavir, Atazanavir, Saquinavir

Side effects - Hyperlipidemias, Fat redistribution and Type 2 Diabetes

Question 23

HIV Treatment - Integration inhibitors - drug names? side effects?

Answer 23

Raltegravir, Elvitegravir

Side effects - Unknown

Question 24

HIV Treatment - 3 classes of Reverse Transcriptase mediated Transcription inhibitors

Answer 24

1) Non-nucleoside Reverese Transcriptase Inhibitors (non-NRTIs)
2) Nucleotide RTI
3) NRTI

Question 25

HIV Treatment - 3 drug examples of Non-NRTIs and their side effects

Answer 25

Nevirapine - can cause Hepatitis and Rash
Delavirdine - can cause a Rash
Efavirenz - can have CNS effects

Question 26

HIV Treatment - Nucleotide RTI - drug name example and side effects?

Answer 26

Tenofovir - can cause bone and renal toxicity

Question 27

HIV Treatment - NRTI - drug name examples and side effects

Answer 27

Zidovudine, Didanosine, Stavudine, Lamivudine, Zalcitabine, Avacavir, Emtricitabine, Epzicom, Combivir, Trizivir

Side effects - Generally rare; feverm headachem GI distrubance, BMS (zudovudine), Peripheral Neuropathy (Zalcitabine, Stavudine), Mitochondrial Toxicity (Stavudine), Hypersensitivity (Abacavir)

Question 28

HIV Treatment - Inhibiting the Docking Process- 2 Classes, drug examples, Side Effects

Answer 28

1) Fusion Inhibitors - Enfuvirtide - can cahse Local reactions to injections and Hypersensitivity
2) Attachment Inhibitors - Maraviroc - side effects unknown