HIV and Antiretrovirals Flashcards
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
When to initiate treatment
ART is recommended for ALL individuals w/ HIV regardless of CD4-Tlymphocyte count
- ASAP if HIV(+)
And transmission Prevention
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
What baseline lab data to have
HIV viral load HIV genotype CD4 count CBC w. Diff CMP
Generic Formula for antiretroviral treatment
3 active antiretrovirals
from at least 2 different antiretroviral classes
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
Pregnancy preferred NRTIs
Lamivudine Emtricitabine Tenofovir (TDF) Abacavir Zidovudine ~ ?
Hep B preferred NRTIs
Lamivudine
Emtricitabine
Tenofovir (TFD & TAF)
Lamivudine
- Class
- Dosing
- Bonuses
NRTI
150mg BID or 300 QD
Reduced replication capacity benefit of m184V mutation
(active against Hep B; preferred in pregnancy)
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)
Tenofovir (TDF) ADRs
Nephrotoxic (avoid in renal insufficiency) GI effects (gas/nausea) Dec. Bone mineral density (avoid in osteoporosis)
Tenofovir (TAF) ADRs
Nausea Diarrhea HA (DO not use for PREP) Strong inducer in rifamycins
Abacavir ADRs
Hypersensitivity Rxn (test for HLA-B*5701 allele) - Never rechallenge Potential Cardiotoxicity
Zidovudine ADRs
Neutropenia
Anemia
GI upset (Take w/ food)
NRTI preferred for M184V mutation
Tenofovir (TDF & TAF)
Zidovudine if M184V AND k65r mutations
NRTI w/ Best CNS penetration
Abacavir
Epzicom
- Combo
- Dosing
Lamivudine + Abacavir combo
1 tablet Daily
Truvada
- Combo
- Dosing
Emtricitabine + Tenofovir (TDF) combo
1 tablet daily
Descovy
- Combo
- Dosing
Emtricitabine + Tenofovir (TAF) combo
1 tablet daily
Combivir (generic now available)
- Combo
- Dosing
Lamivudine + Zidovudine
1 tablet BID
ARV-ARV interaction w/ Atazanavir and Tenofovir
Must be “boosted” with Ritonavir or Cobicistat (PK boosters)
ARV-ARV interaction w/ Didanosine + Tenofovir
Must dose adjust didanosine
ARV-ARV interaction w/ Stavudine + Zidovudine
Antagonistic effect; do not use
Tenofovir Intrxn w/ Ledipasvir
Do not do
Zidovdine intxn w/ Ribavirin
May decrase efficacy of zidovudine
Anemia
Didanosine intxn w/ Ribavirin
Increases didanosine toxicity
Zidovidine Intxn w/ Methadone
May increase zidovudine levels (monitor toxicity)
Didanosine intxn w/ Allopurinol
Contraindicated
increases didanosine levels and toxicity
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
Raltegravir
- Class
- ADR
Integrase Inhibitor
HA (resolves after 2-4wks)
Insomnia, CPK elevation,
Hyperglycemia
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
Dolutegravir
- Class
- ADR
Integrase Inhibitor
Nausesa/bloating, fecal urgency, HA, Insomnia, all generally resolve, mood side effects, hyperglycemia, and increased SCr
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)
Elvitegravir
- Class
- ADR
Integrase Inhibitor
GI upset, Insomnia, HA, Increased SCr (generally not if decreased GFR)
Elvitegravir (bonuses)
- Dosing
Do not use if CrCl <70 mL/min
HIGH-risk for intxns
do NOT use in pregnancy
- 150mg QD w/ food
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
Ritonavir
- Class
- ADR
Protease Inhibitor
GI side effects; Hyperlipidemia, Hyper TG, glucose intolerance
Ritonavir Bonuses
- Dosing
Avoid humidity > 2wks, solution tastes awful
- 100-200mg qd or bid
Darunavir
- Class
- ADR
Protease Inhibitor
GI side effects, LFT elevations, more lipid sparing
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
Atazanavir
- Class
- ADR
Protease Inhibitor
Hyperbilirubinemia (jaundice), LFT elevations, Considered “Lipid sparing”
Atazanavir bonuses
- Dosing
Take w/ Food, ACID suppressant interactions (no PPI or H2RA)
Consider dose inc w/ Ritonavir
Lopinavir/Ritonavir
- CLass
- ADR
Protease Inhibitors
GI side effects, Hyperlipidemia, Hyper TG, Elevated blood glucose
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
Tipranavir
- Class
- ADR
- Bonus/Dose
Protease Inhibitor
Hepatotoxicity, GI side effects, Reports of Intracranial hemorrhage
Take w/ food, Caution in Sulfa Allergies, keep refrigerated
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
Which Protease Inhibitors are CYP 3A4 INDUCERS
Tipranavir + Ritonavir
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)
Efavirenz
- class
- ADR
- Bonuses/dose
non-Nuc
Rash, CNS effects, Insomnia
Avoid high fat content (snack), false pos w/ CBD assays
600mg QD
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
Nevirapine
- Class
- ADR
- Bonuses/dose
Non-Nuc
Rash (SJS) and Hepatotoxicity
Metabolic autoinducer, and Hepatotoxicity risk (if CD4 > 250 in women; >500 in men)
Maraviroc
- Class/Moa
- Requirements
- ADR
CCR5 antagonist - Inhibits Chemotaxis
Requires Tropism Assay
Rash, GI upset, HA, caution in pts w/ history of orthostatic HTN
Cobicistat
- Class/MOA
- ADR
- Bonuses
Pk Booster
inhibits 3A4 and 2D6 metabolism to allow greater pharmacologic effects from other antiretrovirals
Increases SCr
Opportunistic Infections
- Bacterial
- Viral
- Fungal
- Protozoal
- Malignancy
Bacterial - MAC Viral - CMV Fungal - PCP Proto - Toxoplasmosis Gondii Malig - NH Lymph, Burkitts Lymph
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
When to start primary prophylaxis for Toxo Gondii
When to stop?
When Secondary?
Start: CD4 <100
Stop: CD4 >200 x 3mo
2nd: CD4 <200
When to start primary prophylaxis for MAC
When to stop?
When Secondary?
Start: CD4 <50
Stop: CD4 >100
2nd: CD4 <100
When to start primary prophylaxis for CMV
When to stop?
When Secondary?
Start: None
Stop: N/A
2nd: CD4 < 100
Tx for PCP PPx
Bactim/Septra
Tx for Toxo Gondii PPx
Bactrim/Septra
Tx for MAC PPx
Azithromycin 1200mg q wk
Clarithromycin 500mg bid
Azithromycin 600mg biw
Single tablet complete therapy combos
Elvitagrevir + Emtricitabine + Tenofovir (AF) + Cobicistat
Elvitagrevir + Emtricitabine + Tenofovir (DF) + Cobicistat
Dolutegravir + Abacavir + Lamuvidine
all once daily dosing
