Haart

Front 1

what does HAART stand for?

Back 1

highly active anti retroviral therapy =)

Front 2

why is mono or dual therapy not effective for treatment of HIV?

Back 2

- incomplete viral suppression

- drug resistance occurs readily

- poor outcomes (HIV progression --> AIDS --> death)

Front 3

resistance to HAART is directly associated with

Back 3

regimen potency and medication adherence

Front 4

2 reasons why resistance to HAART occurs (how)?

Back 4

1. high level of virus production and turnover
2. reverse trascription is prone to error

Front 5

pathogenesis of resistance "survival of the fittest" ...

Back 5

1. drug susceptible virus is depressed
2. mutated virus survive and fluorish (quasispecies)
3. treatment becomes inneffective
4. viral load increases unchecked :(

Front 6

how long does it take for a mutation to occur?

Back 6

mutations occur daily

Front 7

is there cross resistance to HAART meds? what is cross resistance?

Back 7

yes. Resistance to one agent often confers resistance to others...
Lose multiple treatment options

Front 8

how can one possibly avoid resistance to HAART meds?

Back 8

Vital to avoid resistance and preserve treatment options
1. Adherence is critical**
2. Proper HAART combinations

Front 9

potential advantages of HAART?? (3)

Back 9

1. decrease rate of HIV transmission
2. decrease mother->child transmission of HIV
3. post-exposure prophylaxis

Front 10

to treat or not to treat?
if patient is symptomatic disease?

Back 10

recommend treatment

Front 11

to treat or not to treat?
asymptomatic pt, CD4 200-350

Back 11

offer treatment

Front 12

to treat or not to treat?
asymptomatic pt, CD4 <200

Back 12

recommend treatment

Front 13

to treat or not to treat?
asymptomatic pt, CD4>350, VL >100,000

Back 13

clinical call (3 year risk of AIDS = 30%)

Front 14

to treat or not to treat?
asymptomatic pt, CD4>350, VL<100,000

Back 14

defer treatment

Front 15

to build an initial HAART treatment, how many agents should be used together? and what types of agents?

Back 15

3 agents minimim!

2NRTIs + PI or NNRTI

2NRTIs = backbone

Front 16

factors to consider when choosing HAART treatment:

Back 16

1. pt willingness to start therapy
2. adherence potential
3. pill burden, dosing frequency, food restrictions
4. severity of disease
5. potential AE
6. co-morbidities
7. potential drug interactions

Front 17

1st line preferred treatment regimen (HAART)

Back 17

NNRTI + 2 NRTIs

efavirenz + [lamivudine or emtricitabine] + [zidovudine or tenofovir]

Front 18

alternative NNRTI based HAART regimens

Back 18

Efavirenz + (lamivudine or emtricitabine) + (didanosine or abacavir or stavudine)


Nevirapine + (lamivudine or emtricitabine) + (zidovudine or stavudine or didanosine)

Front 19

preferred initial PI based HAART regimen

Back 19

Lopinavir + Ritonavir (Kaletra®)
Or
Atazanavir + Ritonavir
Or
Fosamprenavir + Ritonavir

AND

Lamivudine or emtricitabine

AND

Zidovudine or tenofovir

Front 20

alternative PI based HAART regimens

Back 20

Atazanavir (with no RTV) or
Fosamprenavir (with no RTV) or
Indinavir/ritonavir or
Nelfinavir or
Saquinavir/ritonavir or

AND

Lamivudine or emtricitabine

AND

Stavudine or didanosine or abacavir or tenofovir

Front 21

other PI based regimen alternatives

Back 21

Lopinavir/ritonavir or atazanavir/ritonavir or fosamprenavir/ritonavir + lamivudine + abacavir

Front 22

what are some advantages of an NNRT-based regimen?

Back 22

less fat malabsorption
less dyslipedimia
less metabolic disorders
conserve PI's for future use

Front 23

disadvantages of NNRT-based regimen?

Back 23

low barrier or resistance, drug interactions, rash, hepatotoxicity with nevirapine*

Front 24

what are some advantages of an PI-based regimen?

Back 24

Conserve NNRTI’s for future use, longest data on survival, greater barrier for resistance

Front 25

disadvantages of PI-based regimen?

Back 25

Metabolic complications, drug interactions, Pill burden (depending upon agent used)

Important to consider advantages/disadvantages of individual PI’s before use

Front 26

concurrent use of stovudine and which drug should be avoided due to antagonism (they inhibit each others ability to work effectively)

Back 26

stovudine + zidovudine

Front 27

didanosine and what drug should be avoided due to additive toxicity (lactic acidosis, peripheral neuropathy)?

Back 27

didanosine + stavudine

Front 28

what dose of ritonavir should be given to pts? how is this drug typically used?

Back 28

LOW dose due to poor tolerance + long term adverse effects

this drug is ONLY used as a BOOSTING drug

Front 29

in what pt population should efavirenz be avoided?

Back 29

in pregnancy b/c its TERATOGENIC!!!!

Front 30

these two drugs should not be used together due to additive hyperbilirubinemia

Back 30

atazanavir + indinavir

Front 31

defined HAART regimen failure is defined by this viral load, in this time frame

Back 31

not achieving VL <400 by 24 weeks OR VL <50 by 48 weeks

Front 32

defined regimen failure; immunologic failure is...

Back 32

<25-50 cell/mm3 CD4 increase over 1st year

a decrease to below baseline CD4 count

Front 33

defined regiment failure; defined clinical failure is...

Back 33

occurrence or recurrence of HIV-related events (at least 3 mo after start of regimen)

Front 34

monitoring with HAART (in regards to VL, CD4)

Back 34

VL: baseline, 2-8wks after intiation of new regimen (should see LOG drop*), q2-4mo thereafter

CD4: baseline, roughly 3-4x/yr

Front 35

undetectable VL is considered ?copies/mL

Back 35

50copies/mL

Front 36

the strongest predictor for HAART therapy failure is...

Back 36

non=adherence...which leads to suboptimal drug efficacy and resistance*

Front 37

rate of VL decline is affected by

Back 37

1. baseline CD4 and VL
2. potency of regimen
3. adherence to regimen
4. previous antiretroviral exposures
5. presence of any opportunistic infections (OIs)

Front 38

two factors required for resistance to develop

Back 38

1. Virus has to be replicating
2. Drug pressure push for resistance

Front 39

resistance testing can be done two different ways; what are they? how often is this done?

Back 39

1. genotyping*
2. phenotyping

this is done in every pt before initiating therapy

Front 40

this type of resistance testing is done by taking persons virus, and looking specifically for mutations; we know what change in virus shows a decreased sensitivity to drugs – look for those changes in viral chain...

Back 40

genotyping

detects resistance mutations on reverse transcriptase and protease genes

Front 41

this type of testing tests virus against specific medications

Back 41

phenotyping

Front 42

3 areas when resistance testing would be done

Back 42

1. before starting therapy to check for transmitted resistance

2. upon regimen (virologic) failure in order to choose the next regimen

3. for subsequent regimen failures

Front 43

rank the following drug classes according to prevalence of resistance (highest --> lowest): NRTI, NNRTI, PI, >2 classes, any class

Back 43

any class > NNRTI > NRTI > (>)2classes > PI


NNRTI—highest risk for resistance w/these drugs

Front 44

in treating HAART experienced patient, what regimens are used?

Back 44

Using agents from all 3 or 4 classes may become warranted at this point
#1. NNRTI + PI + NRTI +/- FI
OR
#2. Multiple active PIs and NRTIs used together

Front 45

these agents are reserved for pts who have developed extensive drug resistance (they are used as salvage therapy)

Back 45

1. Protease inhibitors:
- Darunavir
- Tipranavir

2. Enfuvirtide (T20/Fuzeon) (inj, expensive)

3. Maraviroc

4. Raltegravir

Front 46

if a pt is on HAART, and stops one of the drugs --- is this allowable?

Back 46

NO -- if patient stops taking one med, they should stop them ALL to avoid resistance