Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
65 Cards in this Set
- Front
- Back
|
What are the main reasons for why there is no HIV vaccine?
|
1) Don't know how to make a T cell vaccine
2) High mutation rate of HIV 3) Don't know how to vaccinate well against STDs (ecxeptions: HPV, Hep B) |
|
|
How was this virus transmitted early on to certain people?
|
Through blood transfusion
|
|
|
What was the 1st drug developed against HIV?
|
Zidovudine (AZT/ZDV)
|
|
|
What were the results of using ZDV?
|
It was better than the placebo
It slowed but didn't reverse the disease Ultimately, it was afailure because everyone ended up having resistance to it |
|
|
What were the next drugs introduced onto the market for HIV?
|
3TC
Protease inhibitors |
|
|
What did Merck find out about drug regimes?
|
Triple therapy with 3 drugs worked a lot better than just giving 1 drug
-->Patients lived longer |
|
|
What happened following introduction of protease inhibitors?
|
Major decrease in the number of HIV deaths
-->Shows progress in this disease treatment |
|
|
What is HAART?
|
Highly Active Anti Retroviral Therapy
|
|
|
What did the HAART studies show?
|
That the drug regime was improving
|
|
|
What has the major progress for HIV treatment been?
|
HIV has become a chronic manageable condition for most ppl
|
|
|
What are the problem that still exist with HIV?
|
Drug resistance
Drug toxicities Long term consequences of HIV itself and/or the ARVs |
|
|
Which HIV gene is enough to reconstruct transmission events?
|
Pol gene
|
|
|
What was realized about transmission events?
|
RT and protease sequences are conserved
A single dominant viral species is transmmitted and persists Sequence clustering infers viral inter-relationships |
|
|
Whats the problem with having many different drugs for this virus?
|
People think that they don't need to take any extra precautions against the disease, since they can always get the drugs later
|
|
|
What was noticed when a cohort of new infections were studied?
|
The viruses looked like they could be related to one another (sequence wise)
Found the viral sequences of some infeted ppl clustered |
|
|
How do they know the viruses were similar?
|
3 weeks after infection, the virus is almost monoclonal
Not a lot of variability around it, even if different samples are taken from the same person |
|
|
What happens if you wait a year to take virus samples from an infected person?
|
Get a lot of heterogeneity because the virus has had the chance to mutate
This heterogeneity applies to each gene of the virus |
|
|
Why does HIV have such a high mutation rate?
|
RT always makes mistakes
|
|
|
What does it mean that 1/2 the people who were part of this stufy were clustered together?
|
They had very similar HIV genetic sequences
|
|
|
How can people have such similar genetic sequences of their HIV?
|
They shared common donors in regard to the transmission sequence
=> HIV transmission might be occuring in certain ppl who transmit the virus to others |
|
|
When can this clustering be seen?
|
Only if people are sequenced soon after transmission
|
|
|
Why can clustering only be seen soon after infection?
|
If you wait too long to sequence the virus, it will be very heterogenous
This relative homogeneity will be gone within ~6 months |
|
|
What does this clustering suggest?**
|
** ~ 1/2 og the new infections must be coming from ppl who are themselves newly infected **
==>Newly infected ppl are a major source of NEW HIV infections |
|
|
Are small or large clusters more likely?
What does this mean? |
Small clusters
More likely to have similar sequences between 2-4 people, then 5+ ppl |
|
|
When does an infected person have the highest viral load in their blood?
|
When they're newly infected
Best chance of transmittting this virus within the first 2 months following infection |
|
|
What's the problem with this time of infection?
|
HIV test will be negative
Won't have AB agaisnt the virus |
|
|
What is the one good thing that happens after people become infected?
|
Modify risk behaviour so that they don't infect other people
|
|
|
Why do people fail therapy?
|
Mutations that protect them against the drug
|
|
|
What is the K65R mutation?
|
Mutation in RT
Lysine to Arginine mutation Get resistance against Therofavir |
|
|
For which subtype is this K65R particularly problematic?
|
For the subtype C
(comes up more quickly then for the subtype B) |
|
|
What kind of a drug it ddI/d4T?
|
Nucleoside inhibitors
|
|
|
What kind of drug is 3TC?
|
Nucleoside inhibitor
|
|
|
What kind of a drug is NVP?
|
NNRTI
|
|
|
What is the viral load if someone is failing treatment?
|
Above 50 viral particles/ml of blood
|
|
|
What happened in the Botswana study?
|
Of the 15 ppl who failed treatment, 7 of them had th eK65R mutation
|
|
|
Which mutation is more likely to occur in subtype B?
|
L74V mutation
|
|
|
Where is subtype B prevalent?
|
North America
Europe |
|
|
Why do ppl in developing countries use different drugs than the ones that are available here?
|
They're cheaper
But they don't do very well because they are cheaper |
|
|
What's the problem with d4T?
|
Ass't with a llot of side effects
1) Neurological symptoms 2) Facial disfigurements: get stigmatized |
|
|
What's wrong with these side effects?
|
Makes people stop taking drugs
Can have reactions to the side effects |
|
|
What happens when ppl stop taking the drugs?
|
-->If ppl stop taking the drugs, the virus replicates again and can develop resistance
Select out resistant form of the virus because even after you stop taking the drug, residual drug still hangs around for a while When an inadequate amount of any drug is given, get selective pressure and subvergence of resistant strains |
|
|
Why do 3 drugs work better than one?
|
HIV drug resistance exists before take drugs
-->From the moment you get infected, virus is already going through multiple cycles -->By the time you start therapy, virus has mutated into many different quasi species -->These include species with every single point mutation possible, including against drugs |
|
|
How are drugs being used now?
|
As prevention and treatment
|
|
|
What are they trying to show?
|
If drugs work as treatment, can be used as prophylaxis
-->If you know you're susceptible to HIV, could take HIV drugs and see if you can get the drug level high enough in the plasma Drugs will be in the cells already, .: if the virus does get in, drugs will interfere with the virus the 1st time HIV tries to integrate into the genome .: No risk situation |
|
|
What were some approaches used to show this?
|
Microbicide approach
Prophylaxis |
|
|
Describe the microbicide approach
|
Women in South America
Women at risk for HIV put a sponge soaked in microbicide in their vaginal cavities before intercourse -->Women who did this were protect by 38% |
|
|
Describe the prophylaxis approach
|
Gay men took 1 pill/day of Truvuda (FTC + Tenofavir) everyday for 1 year
-->44% fewer HIV infections |
|
|
What is a newer concept about taking pills as a prophylaxis?
|
Take the pill only the morning before sexual activity (instead of everyday)
|
|
|
What drug was used in the microbicide study?
|
TFV
|
|
|
What is PREP?
|
Pre-exposure prophylaxis approach used by Gay men
|
|
|
How can treatment as a prevention be used in a wide amount of ppl?
|
Treat everybody without screening
Will reduce the viral load in everybody infected and won't have any new infections because people with low viral loads aren't good at transmitting |
|
|
How is this useful for discordant couples (one person is infected and one isn't)?
|
If viral load is low enough, unlikely to transmit to partner
|
|
|
What are some examples of entry inhibitors?
|
T20
Maraviroc |
|
|
Describe T20
|
Needs to be injected
Works by blocking the fusion btw the viral envelope and the cell =surface |
|
|
Where can mutations arise to protect against T20?
|
In GP41 and GP160 env
|
|
|
Describe Maraviroc
|
Blocks CCR5 receptor .: prevents infection of cells
Can't work forever because there's another receptor CXCR4 |
|
|
When is there the highest tropism for the CCR5 receptor?
|
At the start of infection (later on, changes to CXCR4 tropism)
|
|
|
How are ppl infected with HIV monitored here?
|
Look at viral load
|
|
|
How are ppl monitored in developing countries?
|
Look at CD4+ T cell count
|
|
|
Why is there this discrepancy?
|
By the timee someone has a rebounding viral load, they are so full of virus that the rise in viral load precedes the drop in CD4+ T cells by months
-->By the time CD4+ drop, viral load has already gone back up and have resistance |
|
|
Why is looking at the T cell count not the best way to do it?
|
Can't afford to do the viral load test in developing countries
-This way, they can keep them on the same drug longer and then switch if CD4+ decreases Can save the money a d put it towards newer drugs |
|
|
What is the result of waiting to switch the drugs?
|
Can get 2ry infections again
Recombination of different subtypes of HIV (A/C recombination) in the same person |
|
|
What happens if you have K103N mutations in developing countries?
|
Get resistance to NNRTI
--> Viral load inc to 1000 but you don't know because you're not monitoring viral load -->now only 2 drugs left that are working --> But patients are still on all 3 drugs Virus will keep on mutating while replicating .: build-up mutations in the sane virus backbone Get increased resistance and get even more mutations against neveripin (not just K103N) |
|
|
Whats the problem with accumulating all these mutations?
|
Become non-responsive to next generation drug in its class
More mutations accumulated, more likely to get resistance -->Virus can become multi drug resistant |
|
|
Describe NNRTI
|
Approved for use in 1st line therapy may be more fragile than some long term clinical trials
Transmission of NNRTI mutations will continue to increase in settings in which they are being used extensibely |
