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Flashcards in HIV and Antiretrovirals Deck (62):
1

Goals of HIV Tx

- Maximally and durably suppress Plasma HIV RNA, - Restore and Preserve immunologic function
- Reduce HIV associated morbidity and prolong the duration and quality of survival
- Prevent transmission

2

When to initiate treatment

ART is recommended for ALL individuals w/ HIV regardless of CD4-Tlymphocyte count

- ASAP if HIV(+)

And transmission Prevention

3

When to initiate tx (Like now)

Prego
AIDS
Acute opportunistic infection
Low CD4 count
HIV-AN
Acute/Early HIV infection
Hep B or C coinfect

4

What baseline lab data to have

HIV viral load
HIV genotype
CD4 count
CBC w. Diff
CMP

5

Generic Formula for antiretroviral treatment

3 active antiretrovirals
from at least 2 different antiretroviral classes

6

Nucleotide Reverse Transcriptase Inhibitors (NRTI)
- MOA
- Class ADR

Cause premature DNA chain termination during reverse transcription

- Renal Dosing (excp Abacavir)
- Lactic Acidosis
- Hepatic Steatosis
- Peripheral Neuropahy
- Lipoatrophy

7

Pregnancy preferred NRTIs

Lamivudine
Emtricitabine
Tenofovir (TDF)
Abacavir
Zidovudine ~ ?

8

Hep B preferred NRTIs

Lamivudine
Emtricitabine
Tenofovir (TFD & TAF)

9

Lamivudine
- Class
- Dosing
- Bonuses

NRTI
150mg BID or 300 QD
Reduced replication capacity benefit of m184V mutation
(active against Hep B; preferred in pregnancy)

10

Emtricitabine
- Class
- Dosing
- Bonuses

NRTI
200mg QD
May cause skin darkening

Reduced replication capacity benefit of m184V mutation
(active against Hep B; preferred in pregnancy)

11

Tenofovir (TDF) ADRs

Nephrotoxic (avoid in renal insufficiency)
GI effects (gas/nausea)
Dec. Bone mineral density (avoid in osteoporosis)

12

Tenofovir (TAF) ADRs

Nausea
Diarrhea
HA
(DO not use for PREP)
Strong inducer in rifamycins

13

Abacavir ADRs

Hypersensitivity Rxn (test for HLA-B*5701 allele) - Never rechallenge
Potential Cardiotoxicity

14

Zidovudine ADRs

Neutropenia
Anemia
GI upset (Take w/ food)

15

NRTI preferred for M184V mutation

Tenofovir (TDF & TAF)
Zidovudine if M184V AND k65r mutations

16

NRTI w/ Best CNS penetration

Abacavir

17

Epzicom
- Combo
- Dosing

Lamivudine + Abacavir combo
1 tablet Daily

18

Truvada
- Combo
- Dosing

Emtricitabine + Tenofovir (TDF) combo
1 tablet daily

19

Descovy
- Combo
- Dosing

Emtricitabine + Tenofovir (TAF) combo
1 tablet daily

20

Combivir (generic now available)
- Combo
- Dosing

Lamivudine + Zidovudine
1 tablet BID

21

ARV-ARV interaction w/ Atazanavir and Tenofovir

Must be "boosted" with Ritonavir or Cobicistat (PK boosters)

22

ARV-ARV interaction w/ Didanosine + Tenofovir

Must dose adjust didanosine

23

ARV-ARV interaction w/ Stavudine + Zidovudine

Antagonistic effect; do not use

24

Tenofovir Intrxn w/ Ledipasvir

Do not do

25

Zidovdine intxn w/ Ribavirin

May decrase efficacy of zidovudine
Anemia

26

Didanosine intxn w/ Ribavirin

Increases didanosine toxicity

27

Zidovidine Intxn w/ Methadone

May increase zidovudine levels (monitor toxicity)

28

Didanosine intxn w/ Allopurinol

Contraindicated
increases didanosine levels and toxicity

29

Integrase Inhibitors
- MOA
- Class ADR

Inhibits the "strand transfer" phase of HIV DNA integration into the host DNA.

HA, Insomnia, CPK elevation, Nausea, Hyperglycemia?, and Intxns w/ divalent/polyvalent cations

30

Raltegravir
- Class
- ADR

Integrase Inhibitor
HA (resolves after 2-4wks)
Insomnia, CPK elevation,
Hyperglycemia

31

Raltegravir (bonuses)
- Dosing

Lowest risk for infection must increase dose w/ rifampin or other UGT inducers
Preferred Integrase Inhibitor in pregos
400mg BID
1200mg QD

32

Dolutegravir
- Class
- ADR

Integrase Inhibitor
Nausesa/bloating, fecal urgency, HA, Insomnia, all generally resolve, mood side effects, hyperglycemia, and increased SCr

33

Dolutegravir (bonuses)
- Dosing

Low/moderate risk for interactions
High barrier to resistance and active against some resistant virus
- 50mg QD
50mg BID (if suspected integrase inhibitor resistance or with concomitant metabolic inducer)

34

Elvitegravir
- Class
- ADR

Integrase Inhibitor
GI upset, Insomnia, HA, Increased SCr (generally not if decreased GFR)

35

Elvitegravir (bonuses)
- Dosing

Do not use if CrCl <70 mL/min
HIGH-risk for intxns
do NOT use in pregnancy
- 150mg QD w/ food

36

Protease Inhibitors
- MOA
- Class ADRs

Inhibits protease cleaving of gag and gag-pol viral proteins

GI side effects, Hyperlipidemia, Hypertriglyceridemia, Insulin Resistance, 3A4 inxns (inhibition mostly), and Lipodystrophy

37

Ritonavir
- Class
- ADR

Protease Inhibitor

GI side effects; Hyperlipidemia, Hyper TG, glucose intolerance

38

Ritonavir Bonuses
- Dosing

Avoid humidity > 2wks, solution tastes awful

- 100-200mg qd or bid

39

Darunavir
- Class
- ADR

Protease Inhibitor

GI side effects, LFT elevations, more lipid sparing

40

Darunavir bonuses
- dosing

Newest
Take w/ food
No if SULFA allergy Preferred in Pregos

800mg qd w/ booster
OR
150mg QD
OR
600mg BID w/ RTV

41

Atazanavir
- Class
- ADR

Protease Inhibitor

Hyperbilirubinemia (jaundice), LFT elevations, Considered "Lipid sparing"

42

Atazanavir bonuses
- Dosing

Take w/ Food, ACID suppressant interactions (no PPI or H2RA)
Consider dose inc w/ Ritonavir

43

Lopinavir/Ritonavir
- CLass
- ADR

Protease Inhibitors

GI side effects, Hyperlipidemia, Hyper TG, Elevated blood glucose

44

Nelfinavir
- Class
- ADR
- bonus/dose

Protease Inhibitor (alternative tx)

Diarrhea, Hyperlipid/TGemia, LFT and Glucose elevations

Take w/ snack or meal
Only proteasome inhibitor never boosted with RTV

45

Tipranavir
- Class
- ADR
- Bonus/Dose

Protease Inhibitor

Hepatotoxicity, GI side effects, Reports of Intracranial hemorrhage

Take w/ food, Caution in Sulfa Allergies, keep refrigerated

46

Protease Inhibitor general Drug-Drug interactions

CYP 3a4 high risk interaction (inducers)
- No use of Simva or Lovastatin
- Careful w/ corticosteroids
- Careful w/ Hep C meds

Antipyschs (quetiapine)
Antifungals (vori)
Anti-mycobacterium
Benzos
Cardiac Glycosides

47

Which Protease Inhibitors are CYP 3A4 INDUCERS

Tipranavir + Ritonavir

48

Non-Nucleoside Reverse Transcriptase Inhibitors (Non Nucs)
- MOA
- Class ADRs

Bind Reverse transciptase at an allosteric site to inhibir enzymatic activity

Cross Resistance, Low barrier to resistance
Rash, 3A4 induction (except delavirdine)

49

Efavirenz
- class
- ADR
- Bonuses/dose

non-Nuc

Rash, CNS effects, Insomnia

Avoid high fat content (snack), false pos w/ CBD assays
600mg QD

50

Rilpivirine
- Class
- ADR
- Bonuses/dose

Non-Nuc

Less incidence of Rash and CNS effects, may inc SCr, no effect on GFR

Avoid if HIV VL >100,000 or CD4 count <200, Avoid if ACID suppressants, Take w. Food

51

Nevirapine
- Class
- ADR
- Bonuses/dose

Non-Nuc

Rash (SJS) and Hepatotoxicity

Metabolic autoinducer, and Hepatotoxicity risk (if CD4 > 250 in women; >500 in men)

52

Maraviroc
- Class/Moa
- Requirements
- ADR

CCR5 antagonist - Inhibits Chemotaxis

Requires Tropism Assay

Rash, GI upset, HA, caution in pts w/ history of orthostatic HTN

53

Cobicistat
- Class/MOA
- ADR
- Bonuses

Pk Booster

inhibits 3A4 and 2D6 metabolism to allow greater pharmacologic effects from other antiretrovirals

Increases SCr

54

Opportunistic Infections
- Bacterial
- Viral
- Fungal
- Protozoal
- Malignancy

Bacterial - MAC
Viral - CMV
Fungal - PCP
Proto - Toxoplasmosis Gondii
Malig - NH Lymph, Burkitts Lymph

55

When to start primary prophylaxis for PCP/PJP
When to stop?
When Secondary?

Start: CD4 <200
Stop: CD4 >200 x 3mo

2nd : PJP occurred start at >200

56

When to start primary prophylaxis for Toxo Gondii
When to stop?
When Secondary?

Start: CD4 <100
Stop: CD4 >200 x 3mo

2nd: CD4 <200

57

When to start primary prophylaxis for MAC
When to stop?
When Secondary?

Start: CD4 <50
Stop: CD4 >100

2nd: CD4 <100

58

When to start primary prophylaxis for CMV
When to stop?
When Secondary?

Start: None
Stop: N/A

2nd: CD4 < 100

59

Tx for PCP PPx

Bactim/Septra

60

Tx for Toxo Gondii PPx

Bactrim/Septra

61

Tx for MAC PPx

Azithromycin 1200mg q wk
Clarithromycin 500mg bid
Azithromycin 600mg biw

62

Single tablet complete therapy combos

Elvitagrevir + Emtricitabine + Tenofovir (AF) + Cobicistat
Elvitagrevir + Emtricitabine + Tenofovir (DF) + Cobicistat
Dolutegravir + Abacavir + Lamuvidine

all once daily dosing