Antiretroviral Therapy:

Front 1

emtricitabine: (FTC) (preferred use) preferred

Back 1

NRTI: nucleoside analogue, Q day, renal excretion, no drug interactions, few side effects, activity with HBV, in fixed dose combos (Truvuda and atripla)

Front 2

tenofovir (TDF):***side effects: (preferred use) preferred

Back 2

NtRTI: nucleotide; Q day, renal excretion, drug interactions: inc. didanosine and dec atazanavir; side effects:
increase creatinine, increase proteinuria
decrease bone density, HBV activity vs. other viruses

Front 3

lamivudine (3TC): (alternative use) alternative

Back 3

-nucleoside analogue; dosing Q day; renal excretion, no drug interactions, few side effects; also used against HBV: in 3 combo drugs: Combivir, Epzicom, trizivir

Front 4

abacavir: (ABC); (alternative use)alternative

Back 4

-nucleoside; Q day; metabolized by alcohol dehydrogenase in liver; drug interactions: alcohol inc. ABC:
hypersensitivity rxn in 5% screen for HLA-B-5701: fixed combo with Epzicom

Front 5

zidovudine: (AZT) (acceptable use)

Back 5

nucleoside; BID; glucoronidated in the liver; side effects: anemia, granulocytopenia, nauseau; preferred use for PMTCT: combivir and trizivir

Front 6

What are the five nucleoside analogues/ nucleotide analogues used for drugs against HIV:

Back 6

-ET LAZ:
emtricitavine,
tenofovir
lamivudine
abacavir
zidovudine

Front 7

Efavirenz: (with emtricitabine and tenofovir in atripla)

Back 7

; NNRTI of HIV1: Q daily; fatty foods increase absorption; induces some p450 enzymes inhibits others; decreases levels of some drugs and increases others; CNS or psychiatric symptoms in 50% (dizziness, decreased concentration, somnolence, abnormal dreams, insomnia, rash, dyslipidemia, teratogenic); resistance; K103N; Y181C: cross resistance to NVP;
***AVOID in 1st trimester pregnancy or in women with high pregnancy potential

Front 8

rilpivirine: (with FTC and TDF as complera)

Back 8

-Q day; take with 500 calorie meal: absorption depends on lower gastric pH; CYP3a4 is the substrate; H2 blockers and antacids have drug interactions: contraindicated with PPIs, strong CYP3a4 inducer and dexamethasone; side effects: RASH, depression, insomnia, compared with EFV: fewer discontinuations for CNS adverse effects: resistance:

Front 9

Nevirapine: BID:

Back 9

bid; absorpion: induces p450 autoinduction and use 2 week ose escalation; reduces level of many drugs; rash (may be severe); K103N and Y181C: cross resistance to EFV: aoid in women with nadir CD4> 250 and in menw with nadir CD4> 400; in mod severe liver disease; but it IS an important component for PMTCT:

Front 10

What are important features of the class of drugs: nucleoside inhibitors:

Back 10

-drug must be triphosphorylated within cells to active compound
-competitive inhibition and chain termination
-phosphate has a longer half life than parent compound
-mechanism of resistance: single or multiple base pair mutations in RT

Front 11

What are the four NNRTI of HIV-1 to know?

Back 11

ERNE:
Efavirenz'
rilpivirine
nevirapine
etravirine

Front 12

Efavirinz: preferred

Back 12

Q; daily: drug interactions: dec levels of some drugs and increases others;
side effects: CNS or psychiatric symptoms in 50% of patients (dizziness, decrease concentration, abnormal dreams, rash and dyslipidemia: TERATOGENIC);
resistance: K103N and Y181C: (cross resistance to nevirapine)

***AVOID in first trimester of pregnancy or in women of high pregnancy potential

Front 13

Rilpivirine:alterantive

Back 13

Q daily: take with 500 calorie meal; absorptoin depends on lower gastric PH: CYp3A4 substrate
-drug interactions with H2 blockers, antacids,
-side effects: Rash, depression, insomnia, headache, but fewer discontinuations than EFZ for CNS adverse effects
-resistance: more mutations at virologcal failure than regimein with EFV + 2 NRTIs
-not recommended in patients with high viral loads
-use of proton pump inhibitors is contraindicated

Front 14

Nevirapine: accpetable

Back 14

BID, induces P450 autoinduction use 2 week dose escalation;
-drug interactions: increases anti-TB meds; decrease others
side effects (rash and hepatitis)
-resistance: cross resistance to EFV K103 N and Y 181 C
avoid in women with nadir CD4 > 250 and men with nadir CD4> 400; in moderate to severe liver disease
***USE OF PMTCT

Front 15

etravirien: acceptable

Back 15

BID; induces p450 enzymes; many drugs interactions; side effects: Rash and nauseau
resistance: fully active vs. K103N mutants that are resistant ; NEED multiple mutations to get Y 181 C
****TREAT ONLY EXPERIENCED PATIENTS!!!!

Front 16

features of NNRTI of HIV-1

Back 16

potent inhibitors of HIV-1 not HIV-2; rash is a side effect common to the class; low genetic barrier to resistance: single point mutation causes resistance (efavirenz nevirapine)

Front 17

HIV protease inhibitor features:

Back 17

-target viral protease
-mechanism of action: inhibit proteolysis of gag and gag pol proteins
-progeny virions are non-infectious all are metabolized by cytorchrome p450 hepatic enzyme
-numerous drug interactions
-ritonavir boosting; small doses of ritonavir inhibit p450 metabolism and incereasetrough and AUC of a second PI and cobicistat
-boosted PI's have a low rate of breakthrough virus due to high trough concentrations
-metabolic effects of protease inhibitors: hyperglycemia, hyperinsulenamia, dm;

Front 18

what are five protease inhibitors we need to know:

Back 18

ADFLS: atanavir, darunavir, Fos-amprenavir, lopinavir:

Front 19

atazanavir: (preferred)

Back 19

side effects: increased unconjugated bilirubin due to inhibited UDP-lucoronysyl transferase (UGT); ose related esp. with RTV boost/ reports of nephrolithiasis

-miscelaneous: signature mutation 150L; need to take with food: preferred component with PMTCT; coadminister with 100 mg/day RTV

Front 20

darunavir: (preferred)

Back 20

diarrhea, nauseau, rash (sulfa)

-misc: food requirement; take with food and coadminister with 100 mg/day rtv

Front 21

fos-amprenavir: alternative

Back 21

-diarhea, headache, hyperlipidemia and rash (sulfa)
-prodrug of amprenavir and co-administer with 100 mg/day rtv

Front 22

lopinavir: alternative

Back 22

diarrhea, NV< hyperlipidemia:
-fixed dose combo: 200 mg+ 50 mg rtv (in small pill); disadvanage is 200 mg/ day rtv ; but preferred component of PMTCT

Front 23

maraviroc:

Back 23

-ccr5 antagonist:
-BID
-substrate of p450 cyp 3A4 and pgp
-orthostatic hypotension, concern esp with renal or hepatic dysfunction
-mutations in V3 loop of HIV env

Front 24

raltegravir: (preferred)

Back 24

integrase inhibitor
-bidaily; metabolized by UGT:
-side effects: inc CPK generally well tolerated: rash
-low genetic barrier to resistance
-use with two other agents

Front 25

elvitegravir (alternative)

Back 25

-interase inhibitor
-once daily boosted with cobicistat in quad pill with tenofovir and emtricitabine
-BOOSTER:
-FDA approved in august 2012:
-side effects: mild rise in serum creatinine

Front 26

CORNERSTONES OF ANTIRETROVIRAL THERAPY:

Back 26

1.) tenofovir + emtricitabine (truvuda)
2.) lamivudine + abacavir (epzicome)
3.) lamivudine + zidovudine (acceptable) ; combivir
4.) COMPLERA = tenofovir + emtricitabine + rilpivarine

Front 27

What composes truvuda?

Back 27

ET: emtricitable Tenofovir

Front 28

What composes atripla?

Back 28

ETE: emtricitavine, tenofovir + enfavirenz