Id Therapeutics Exam 2 Set 4

Front 1

AIDS defining Clinical Conditions (6)

Back 1

1. Mainly Opportunistic Infections
2. Pneumocystis jiroveci pneumonia
3. Toxoplasmosis
4. Mycobacterium avium complex
5. Cytomegalovirus (CMV) infection
6. Cryptococcosis

Front 2

transmission: high risk (3)

Back 2

1. blood
2. semen
3. vaginal secretions

Front 3

Primary HIV Infection: Common Signs & Symptoms (7)

Back 3

1. fever
2. headache
3. lethargy
4. myalgias
5. adenopathy
6. pharyngitis
7. rash

Front 4

How would you monitor viral load in untreated HIV patients

Back 4

time of diagnosis and every 3-4 months

Front 5

How would you monitor viral load in treated HIV patients

Back 5

1. immediately prior to and 2-8 weeks after initiation of ARV therapy
2. every 3-4 months to evaluate effectiveness of therapy

Front 6

at what CD4 count would you consider starting therapy?

Back 6

~350

** pt needs to be ready to start and ready to commit to therapy

Front 7

When would you monitor CD4 in HIV patients

Back 7

1. upon diagnosis
2. every 3-6 months

Front 8

NRTI (7)

Back 8

Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zidovudine

Front 9

NNRTI (5)

Back 9

Delavirdine
Efavirenz
Nevirapine
Etravirine
Rilpivirine

Front 10

protease inhibitors (9)

Back 10

Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir/ritonavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir

Front 11

Fushion inhibitor (1)

Back 11

enfuvirtide

Front 12

CCR5 co-receptor antagonist (1)

Back 12

maraviroc

Front 13

integrase inhibitor (2)

Back 13

elvitegravir
raltegravir

Front 14

PK enhancer (1)

Back 14

cobicistat

Front 15

1. Lactic acidosis and hepatic steatosis
Rare, but high mortality
Evidently due to mitochondrial toxicity
2. Treatment: discontinue ARVs, supportive care
3. Lipodystrophy

Back 15

NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine)

1. Lactic acidosis and hepatic steatosis (higher incidence with stavudine)
*****Stavudine>didanosine=zidovudine>tenofovir=abacavir=lamivudine=emtricitabine
****Rare, but high mortality
*****Evidently due to mitochondrial toxicity
2. Treatment: discontinue ARVs, supportive care
3. Lipodystrophy (higher incidence with stavudine)

Front 16

1. 300 mg q12h or 600 mg daily with or without food (available in combination tablets)
2. Description of hypersensitivity syndrome
Rash or >2 of the following:
fever
nausea, vomiting, diarrhea, abdominal pain
extreme tiredness, achiness, generally ill-feeling
sore throat, shortness of breath, cough,
3. Important to alert patient to contact healthcare provider before stopping it, otherwise high likelihood of “losing it” (not being able to use in future)
4. If possible, screen for HLA-B*5709 before treatment with ____; ____ should not be given to patients positive for HLA-B*5709

Back 16

abacavir

Front 17

NRTI
1. 400 mg daily (EC) unless on tenofovir or < 60 kg
2. ***Empty stomach required
3. Adverse effects: GI intolerance, Pancreatitis, Peripheral neuropathy
4. Pregnant women may be at increased risk for lactic acidosis and liver damage when treated with stavudine and _____. This combination should be avoided in pregnant women, if possible.

Back 17

didanosine

Front 18

NRTI
1. 200 mg daily with or w/o food
2. Structurally identical to lamivudine with addition of fluorine
3. extended t1/2 (10 vs. 3-6 hrs serum t1/2; 39 vs. 12 hrs intracellular t1/2 )
4. Adverse effects similar to lamivudine
5. Primarily eliminated by the kidneys
6. Available in combination tablets

Back 18

emtricitabine

**avoid in renal failure/insufficiency?

Front 19

NRTI
1. 150 mg q12h or 300 mg daily
2. Administer with or without food
3. Well-tolerated
4. Nausea, fatigue, headaches
5. Rare alopecia
6. Available in combination tablets

Back 19

lamivudine

Front 20

NRTI
1. 40 mg q12h unless < 60 kg
2. Administer with or without food
3. Peripheral neuropathy
4. Pancreatitis
5. Pregnant women may be at increased risk for lactic acidosis and liver damage when treated with _____ and didanosine. This combination should be avoided in pregnant women, if possible.

Back 20

stavudine

**avoid in pregnancy

Front 21

NRTI
1. 300 mg once daily with or without food
2. Very little cross-resistance
3. Adverse effects: Headache, GI intolerance, Renal impairment
4. Available in combination tablets

Back 21

tenofovir

**well tolerated

Front 22

NRTI
1. 300 mg q12h with or without food
2. Adverse effects: Initial nausea, Initial ill feeling, Fatigue, headache, GI intolerance: usually resolve 2-4 weeks after initiation
3. *****Bone marrow suppression
4. Available in combination tablets

Back 22

zidovudine

***monitor WBC while on therapy (due to BMS)

Front 23

NNRTI
1. 400 mg q8h
2. Administer with or without food
3. Rash similar to nevirapine, lower incidence

Back 23

delavirdine

Front 24

NNRTI
1. 600 mg qhs
2. Empty stomach
3. CNS Side Effects--Dizziness: reason for HS dosing; Vivid dreams: warn patients; Depression (Think twice in patients with Hx of serious mental illness); Dose-splitting options, take earlier in evening
4. Rash (Generally mild and self-limited)
5. Teratogenic in non-human primates (FDA Pregnancy Category D)

Back 24

efavirenz

**avoid in depression and pregnancy

Front 25

NNRTI
1. 200 mg q12h or 400 mg daily with or w/o food
2. Rash--Management: Requires frequent monitoring to assess whether patient may continue or must stop, rash in up to 1/3 of patients; Dose escalation can help prevent
3. Keep in mind concern of “Stevens-Johnson” with desquamation of cutaneous and mucus membranes (<1%)
4. Hepatotoxicity--May be severe and life-threatening; May develop relatively quickly after start; Pay particular attention to women co-infected with Hepatitis C ***Because of higher rates of hepatotoxicity, ____should not be initiated in women with pre-_____ CD4 counts >250 cells/mm3 or men with CD4+ T cell counts >400 cells/mm3, unless the benefit clearly outweighs the risk

Back 25

nevirapine

Front 26

NNRTI
1. available in tablet formulation; also is available in combination with emtricitabine and tenofovir as a single tablet (Complera, Eviplera).
2. interacts with a number of antiretroviral medications
3. No dosage adjustment is necessary in renal insufficiency.

Back 26

rilpivirine

**DDI with other antiretrovirals!!!

Front 27

side effects of protease inhibitors (9)

Back 27

1. GI side effects
2. Hyperlipidemia* (except atazanavir)
3. Lipodystrophy (fat maldistribution)
4. Elevated liver function tests
5. Hyperglycemia*, insulin resistance and diabetes
6. Bone density
7. Possible increased bleeding risk in hemophiliacs
8. Drug interactions
9. Hepatically metabolized

Front 28

NNRTI
NNRTI with high barrier to resistance
1. 200 mg (two tablets) twice daily
2. Adverse effects: nausea, rash
3. Interactions: 2C9, 3A4, 2C19 substrates, inhibitors, or inducers
don’t coadminister with: Unboosted PI’s; Boosted atazanavir, fosamprenavir, tipranavir; NNRTI’s
4. Efficacy: DUET Study--200 mg bid + BR vs. placebo + BR
Patients with >1 NNRTI mutation and >3 primary PI mutations
VL > 5000 and stable therapy > 8 weeks
5. Even in absence of any other fully active agents, 45% had VL <50
Higher responses with ___ irrespective of baseline VL or CD4

Back 28

etravirine

Front 29

PI
1. 400 mg daily (PI-naïve only); boosted regimen of 300 mg with ritonavir 100 mg daily
2. Administer with food
3. Unlikely to be effective in patients who have failed other PI’s unless ritonavir-boosted
4. Increased bilirubin → yellowing: d/c not required
5. Prolonged PR interval
6. Nephrolithiasis
7. Does not inc. lipids like other PI’s can
8. Interactions: acid needed for absorption

Back 29

atazanavir

Front 30

PI
1. Twice daily: 600 mg with ritonavir 100 mg
2. Once daily (ARV-naïve only): 800 mg with ritonavir 100 mg
3. Administer with food
4. Developed to have activity against resistant virus; low levels cross-resistance
5. Diarrhea, nausea, headache, hepatotoxicity, transaminase elevation
6. Rash (7%), Stevens-Johnson syndrome and erythema multiforme have been reported, has a sulfonamide moiety (avoid in sulfa allergy)

Back 30

darunavir

Front 31

PI
1. Dosing: Therapy-naïve patients--1400 mg bid; 1400 mg + ritonavir 200 mg qd; 700 mg + ritonavir 100 mg bid; PI-experienced or on efavirenz--700 mg + ritonavir 100 mg bid
2. With or without food
3. Rash (19%), potential for sulfa cross-allergy
4. Nausea/vomiting/diarrhea, headache, Transaminase elevation

Back 31

Fosamprenavir

Front 32

PI
1. Dosing: 800 mg q8h vs 800 mg q12h + ritonavir 100-200 mg q12h; 3 periods of food restriction vs none
2. Hydration!
3. Nephrolithiasis
4. GI intolerance, nausea
5. Hyperbilirubinemia
6. Headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia

Back 32

inidinavir

Front 33

PI
1. 400/100 mg (2 tablets) q12h
2. 800/200 mg (4 tablets) daily for naïve patients only
3. 600/150 mg q12h with efavirenz or nevirapine
4. Liquid formulation with food; tablet with or without
5. GI intolerance, nausea, vomiting, diarrhea
6. Asthenia
7. Elevated serum transaminases

Back 33

lopinavir/ritonavir

Front 34

PI
1. 1250 mg q12h with food
2. Diarrhea!
3. Best advice is to take after a substantial meal
4. Usually not accompanied with any other complaint
5. Responds to loperamide well, some use calcium carbonate 500 mg q12h
6. Serum transaminase elevation

Back 34

nelfinavir

Front 35

PI
1. Combination with all other protease inhibitors except nelfinavir
2. Full dose (600 mg q12h with food) rarely used due to GI Sx and drug interactions
3. Hepatitis
4. Must be refrigerated in pharmacy, OK out 30 days
5. Strong inhibitor of P-450*
6. Drug-drug interactions—many!

Back 35

ritonavir

Front 36

PI
1. 1000 mg q12h + ritonavir 100 mg q12h within 2 hours of a meal
2. GI complaints: nausea, gas, bloating, cramps, and diarrhea--Symptomatic treatment; If occurs, becomes more tolerable over time; Amount of food prior to Rx
3. Headache, elevated transaminase enzymes

Back 36

sequinavir

Front 37

PI
1. 500 mg q12h + ritonavir 200 mg q12h
2. Refrigerate until bottle opened; room temp OK for 60 days
3. Rash – more common in women; sun sensitivity; sulfonamide moiety
4. Hepatotoxicity – clinical hepatitis including hepatic decompensation has been reported, monitor closely, esp. in patients with underlying liver disease
Intracranial hemorrhage

Back 37

tipranavir

Front 38

1. In Nov. 2010 the FDA approved _____to treat HIV patients with liposystrophy.
2. _____is a growth hormone releasing factor administered by once-daily injection.
3. It is not known if this drug decreases the risk of cardiovascular disease.
Side effects include joint pain, injection site reactions, stomach pain, swelling, muscle pain and possibly worsening blood glucose control.

Back 38

egrifta (tesamorelin)

Front 39

counseling for enfuvirtide (5)

Back 39

1. Rotate administration sites (abdomen, upper thighs, upper arms)
2. Massage the area
3. Warm wet washcloth
4. Shower before injection
5. Preparation of injection

Front 40

1. 300 mg bid; 150 mg bid with CYP3A4 inhibitors including Protease inhibitors except tipranavir, Delavirdine, Ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone; 600 mg bid with CYP3A4 inducers (without a CYP3A4 inhibitor) including Efavirenz and nevirapine
Rifampin and rifabutin 600 mg q12h with ritonavir 100 mg q12h
2. Adverse effects: abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension
3. Increased efficacy versus patients receiving OBT alone

Back 40

maraviroc

Front 41

Integrase Inhibitor
1. was granted approval by the U.S. Food and Drug Administration (FDA) in August 2012 as part of a coformulation that also includes the pharmacokinetic enhancer COBICSTAT and the two nucleoside/nucleotide analogues (NRTIs) TENOFOVIR and EMTRICITABINE.
2. has recognized interactions with several antiretroviral medications and the combination of ____ + cobicistat (or ritonavir) interacts with a number of antiretrovirals
4. combination should not be initiated in patients with CrCl <70 mL/min and should be discontinued in those with CrCl <50 mL/min. Dosage adjustment for mild or moderate hepatic impairment is not required. No data are available to guide use in persons with severe liver disease.

Back 41

Elvitegravir

Front 42

integrase inhibitor
1. FDA approval of first integrase inhibitor October 12, 2007, in 2012 approved for kids > 2 yrs
2. Blocks integrase, a protein that HIV needs to insert its DNA into the human DNA genome, thus blocking HIV’s ability to replicate
3. 400 mg q12h
4. Drug interactions: Primarily metabolized by glucuronidation (UGT1A1) and has no inhibitory or inductory potential in vitro. Rifampin can decrease concentrations.
5. Adverse effects: nausea, headache, diarrhea, pyrexia, CPK elevation

Back 42

raltegravir

Front 43

monitoring antiviral toxicity

fasting lipids should be tested at ____, _____ after starting ARVs, then every _____

Back 43

1. baseline
2. 2-8 weeks
3. 6-12 months

Front 44

monitoring antiviral toxicity

renal function/ electrolytes should be measured with _____, ______

Back 44

1. indinivir
2. tenofovir

Front 45

monitoring antiviral toxicity

urinalysis should be done every 12 months with ____

Back 45

1. tenofovir

Front 46

monitoring antiviral toxicity

pregnancy tests at baseline if starting ___

Back 46

efavirenz

Front 47

preferred NNTRI regimen (1)

Back 47

1. efavirenz/tenofovir/emtricitabine

Front 48

preferred PI regimen (2)

Back 48

1. atazanavir/ritonavir + tenofovir/emtricitabine
2. darunavir/ritonavir + tenofovir/emtricitabine

Front 49

preferred INSTI-based regimen (1)

Back 49

1. raltegravir + tenofovir/emtricitabine

Front 50

AVR NOT RECOMMENDED FOR INITIAL TREATMENT

High rate of early virologic failure (2 drugs used together)

Back 50

Didanosine + tenofovir

Front 51

AVR NOT RECOMMENDED FOR INITIAL TREATMENT

Inferior virologic efficacy (6)

Back 51

Abacavir/lamivudine/zidovudine as a 3-NRTI regimen
Atazanavir + didanosine + emtricitabine
Delavirdine
Nelfinavir
Saquinavir as sole PI (unboosted)
Tipranavir (ritonavir-boosted)

Front 52

AVR NOT RECOMMENDED FOR INITIAL TREATMENT

High incidence of toxicities (3)

Back 52

Indinavir (ritonavir-boosted)
Ritonavir used as sole PI
Stavudine + lamivudine

Front 53

AVR NOT RECOMMENDED FOR INITIAL TREATMENT

High pill burden/Dosing inconvenience (2)

Back 53

Indinavir (unboosted)
Nelfinavir + saquinavir

Front 54

AVR NOT RECOMMENDED FOR INITIAL TREATMENT

Lack of data in initial treatment (7)

Back 54

Abacavir + tenofovir
Abacavir + didanosine
Darunavir (unboosted)
Enfuvirtide
Etravirine
Maraviroc
Raltegravir

Front 55

AVR NOT RECOMMENDED FOR INITIAL TREATMENT

No benefit over standard regimens (2)

Back 55

3-class regimens
3 NRTIs + NNRTI

Front 56

Antiretroviral Medications: Should not be offered at any time (3)

Back 56

1. Monotherapy with NRTI
2. Dual NRTI therapy
3. 3-NRTI regimen (except abacavir/lamivudine/ zidovudine and possibly lamivudine/zidovudine + tenofovir in selected patients where other regimens are not desirable)

Front 57

Antiretroviral Medications: Components should not be offered at any time (9)

Back 57

1. Didanosine + stavudine
2. Emtricitabine + lamivudine
3. Stavudine + zidovudine
4. Darunavir, saquinavir, or tipranavir as single PIs (unboosted)
5. 2 NNRTI-combination
6. Efavirenz in pregnancy and in women with significant potential for pregnancy
7. Nevirapine initiation in women with CD4>250 or men with CD4>400
8. Etravirine + unboosted PI
9. Etravirine + ritonavir-boosted atazanavir, fosamprenavir, or tipranavir

Front 58

if change required in AVR regimen do to intolerancewhat do you do?

Back 58

substitute agent in same class with different toxicity profile

Front 59

if change required in AVR regimen for failure of current regimen what do you do?

Back 59

use AT LEAST 2 new drugs

Front 60

Factors Associated with Poor Adherence (15)

Back 60

1. Low levels of literacy

Certain age-related challenges
2. Vision loss
3. Cognitive impairment

Psychosocial issues
4. Depression
5. Homelessness
6. Lower social support
7. Stressful life events
8. Dementia
9. Psychosis
10. Active substance abuse
11. Stigma
12. Difficulty with medication taking (Trouble swallowing pills, Daily schedule issues)
13. Complex regimens (Pill burden, Dosing frequency, Food requirements)
14. Adverse drug effects
15. Treatment fatigue

Front 61

Predictors of Good Adherence (7)

Back 61

1. Emotional and practical supports
2. Convenience of regimen
3. Understanding of the importance of adherence
4. Belief in efficacy of medications
5. feeling comfortable taking medications in front of others
6. Keeping clinic appointments
7. Severity of symptoms or illness