HIV ART Treatment Flashcards
What is the structure of a typical ART regimen
2 NRTIs
+
either
- INSTI
- PI + PK enhancer
- NonNRTI
What are the 6 NRTIs
- Tenofovir disoproxil fumarate (TDF)
- Tenofovir alafenamide (TAF)
- Emtricitabine (FTC)
- Lamivudine (3TC)
- Abacavir (ABC)
- Zidovudine (ZDV)
TT ELAZ
What are the 5 NNRTIs
- Doravirine (DOR)
- Rilpivirine (RPV)
- Efavirenz (EFV)
- Nevirapine (NVP)
- Etravirine (ETR)
DRE NE
What are the 3 Protease inhibitors
Darunavir/r or /c (DRV)
Atazanavir (ATV)
Lopinavir (LPV)
-vir
LAD
What are the 5 INSTI (integrase strand transfer inhibitor)
-gravir
- Raltegravir (RAL)
- Elvitegravir (EVG)
- Cabotegravir (CAB)
- Dolutegravir (DTG)
- Bictegravir (BIC)
What are the 4 attachment and entry inhibitors
- Enfuvirtide (T-20)
- Maraviroc (MVC)
- Fostemsavir (FTR)
- Ibalizumab (IBA)
What drug is a Capsid inhibitor
- Lenacapavir
(LEN)
Differentiate between the 2 PK boosters Ritonavir and Cobicistat
Availability/usage
Enzyme inhibition/induction
ADR
anti-HIV activity?
Ritonavir
Availability
- used with many PIs
- single entity drug
Enzyme
- Potent CYP3A4
- has induction effects
ADR
- GI effects
- insulin resistance
- hyperlipidemia
HIV activity?
- Anti-HIV activity at higher doses
Cobicistat
Availability
- Used with PIs atazanavir, darunavir & elvitegravir (INSTI)
Enzyme inhibition
- CYP 3A4
- no induction effects
ADR
- GI effects
- inc Screatinine without affecting GFR
HIV activity?
- None
What are the 3 options for triple drug regimens in Newly diagnosed HIV patients who are treatment naive
TAF / FTC / Bictegravir
TAF / FTC + Dolutegravir
TDF / FTC + Dolutegravir
FTC = emtricitabine
When can you give double therapy in newly diagnosed patients (3)
Which ones to give
- No HBV co-infection
- No resistance
- HIV RNA < 500,000 copies/mL
Lamivudine 3TC + Dolutegravir
What options of treatment are for HIV patients if they used
Cabotegravir for prep
+ no resistance test results are back (4)
Add Protease inhibitor + Booster
TAF / FTC / Darunavir / cobicistat
TDF / FTC + Darunavir / cobicistat
TAF/ FTC + Darunvair + Ritonavir
TDF / FTC + Darunavir + Ritonavir
Which drugs/classes cause weight gain
INSTI
+
TAF
NRTI
TDF vs TAF
Advantages
Disadvantages
Dose + renal dose
TDF
Adv
- favourable lipid effects
Disadv
- Decline in kidney function
- BMD reduction
Dose
- 300mg
- CrCl <50 = less frequent dosing intervals
TAF
Adv
- Favourable effects on renal markers & BMD
Dose
- 10mg daily with PI & booster
- 25mg daily with non-booster
- TAF not recommended CrCl <30
Wha is the dosing for other NRTIs such as Embtricitabine (FTC) and Lamivudine (3TC)
Embtricitabine (FTC)
- 200mg
- available only as combo product
Lamivudine (3TC)
- not really used
- 300mg
- Flexible renal dosing
What are important things to note when treating HIV with HBV co-infection
If Hep B co-infection, need 2 drugs that are active against Hep B
- TAF/TDF + FTC/3TC
**Cannot discontinue those therapies as it may cause serious hepatocellular damage which can reactivate Hep B
Why is abacavir not recommended as first line anymore (3)
HLA B*5701 testing required (takes >7 days and we want to start ARV within 7 days of diagnosis)
Risk of abacavir hypersensitivity syndrome
*NO association with CV disease – meta-analysis proved this association is wrong
What is the abacavir hypersensitivity syndrome
Symptoms
- Potentially life-threatening, multi-system reaction
- Non-specific sx: fever, rash, GI, malaise, respiratory issues
- Median onset: 9 days
- Symptoms worsen with continuation of abacavir
- Stopping abacavir will prompty reverse HSR
HLA-B* 5701 testing:
* Positive result has a strong association (40-50% chance) to abacavir HSR
Screening for patients is required ONCE in their lifetime
What is the dosing for the 2 main INSTI we use
Bictegravir (BIC)
- 50mg
Doulegravir
- Tx naive: 50mg daily
- INSTI resistance or INSTI naive w/ booster: 50mg BID
ADRs with bictegravir
WEIGHT GAIN
Headache
Diarrhea
Nausea
ADRs with Dolutegravir
WEIGHT GAIN
Headache
Insomnia
Depression & suicidal ideation (rare)
What is the main reaction that occurs with Bictegravir and dolutegravir
False CrCl elevation
Follow up on CrCl at 1 month: this becomes new baseline
Due to inhibitor of renal proximal tubule secretion of creatinine
When can raltegravir + 2 NRTIs be preferably used (3)
- Pregnancy
- Chemotherapy
- TB treatment
What is the main alternate treatment if a patient cannot use an INSTI (usually due to weight gain)?
Dose?
Use a PI + booster: Darunavir
- Treatment naive/Pi naive
- 800mg daily
- w/ ritonavir 100mg daily or cobicistat 150mg - Treatment with 1 of 11 darunavir resistance associated mutations (RAMs)
- 600mg BID
- w/ ritonavir 100mg BID
Why is the PI Atazanavir not used anymore as an alternate for INSTI? (3)
- Moderate barrier to resistance
- Low gastric pH required (PPI interaction)
- Bilirubin elevates (surrogate marker for adherence)
What is the dosing for atazanavir
300mg PO daily with:
- Ritonavir 100mg PO daily
400mg PO daily
- NO BOOSTER
What is the reaction between atazanavir and bilirubin
Enzyme?
Symptoms?
Treatment?
Reversible/irreversible?
- Blocking UGT 1A1 causes unconjugated hyperbilirubinemia (which is BENIGN)
Symptoms:
- Causes some yellowing of the skin, eyes – consider this if a patient has a co-infection with Hep B
Treatment
- Does NOT require management
Reversible
- Elevation in indirect bilirubin is REVERSIBLE when stopping atazanavir (this is independent of liver toxicity)
What are common PI side effects
Hyperlipidemia (esp triglycerides)
- CV risk with some
GI intolerance: nausea, diarrhea
What is the other option if INSTI (like weight gain) is not preferred? (2)
Dose
food requirements
DoraVIRine (DOR)
- Resistance to both DOR and NRTIs at virologic failure
- 100mg daily
- with our without food
RilpiVIRine (RPV)
- 25mg daily
- With A BIG meal
- PPI interaction
Why is Efavirenz not used anymore as an NNRTI option instead of INSTI (4)
- Resistance
- Can cause ABNORMAL VIVID DREAMS
- CNS: dizziness, headache, depression, suicidality, somnolence, insomnia
- Skin rash: Occurs within 2 weeks of starting treatment (resolves within 1 month while on treatment)
- Lipids: Can increase LDL and TG
What is the greatest predictor of mother-to-child transmission
High maternal viral load
What are benefits to achieving and maintaining viral suppression on ART in pregnancy
- optimize Mother’s health
- Prevent transmission to baby (biggest transmission occurs during labour – but can occur at any time during pregnancy)
- Prevent postpartum transmission through breastfeeding
- Prevent transmission to serodiscordant partner
What are the preferred treatment for pregnancy in HIV (3)
TAF + FTC + Dolutegravir
TDF + FTC + Dolutegravir
If INSTI intolerance, use PI + booster
- use Darunavir-ritonavir
What is an alternate regimen for pregnancy?
Zidovudine
Efavirenz
Raltegravir
Atazanavir-ritonavir
What is the baseline monitoring for all HIV treatments with labwork (7)
- Basic metabolic panels (lytes, creatinine)
- ALT, AST, total bilirubin
- CBC with differential
- LIPID profile
- Random or fasting glucose
- Urinalysis
- Pregnancy test
Which lab values do you monitor 4-8 weeks after initiation/modifcation
- Basic metabolic panels
- ALT, AST, total bilirubin
- Lipid profile
Which drug switching have the lowers risk of virologic failure
- NRTI: TDF to TAG
- NNRTI: Efavirenz to rilpivirine
- INSTI: Raltegravir to dolutegravir
- Booster: Ritonavir to cobicistat
What are good reasons to switch a patient their ART regimen (7)
- Reducing pill burden
- enhance tolerability and decrease toxicity
- prevent DDI
- Eliminate food/fluid requirements
- Pregnancy
- Reduce costs
- need for a switch to a long-acting injectable
Which switching has higher risk of virologic failure
Not within class:
- Boosted PI to NNRTI (Rilpivirine)
- Boosted PI to INSTI (Raltegravir)
- Dolutegravir to elvitegravir/c (not usually used)
What is the monitoring plan for after switching ART
Clinical monitoring for 3 months after ARV switch
- At 1-2 weeks: check for tolerability & adherence
- At 4-8 weeks: repeat VL (check for rebound viremia)
- At 3 months: can resume to normal monitoring schedule (in absence of new complications, lab abnormalities, viral rebound)
When can you switch a patient do the new long-acting IM injection? (2)
Criteria? (5)
- virologically suppressed on ART 3+ months
- do no want to take PO daily
Criteria
- no baseline resistance to either medication
- No prior virologic failures
- No active Hep B (requires 2 NRTIs)
- Not pregnant
- Not receive meds with significant DDI with PO
- not receiving injectable cabetogravir or rilpivirine
What drugs do we give IM
Administration?
Combo INSTI + NNRTI
Cabotegravir + Rilpivirine
Administration
- bring to room temp 6 hours
- inject in each cheek
What do you monitor in IM injections
Viral load 4-8 weeks after switch
Test for resistance
What is the monthly dosing schedule for IM
Can do oral lead-in for 28+ days
- initiate injection on last day of PO-period
Initial injection
Cabotegravir (600mg): 3mL IM
+
Rilpivirine (900mg): 3mL IM
Every month (+/- 7 days)
Cabotegravir (400mg): 2mL IM
+
Rilpivirine (600mg): 2mL IM
What is the q2month dosing schedule for IM treatment
Initial injection x1
* At month 2
* At month 3
Cabotegravir (600mg): 3mL IM
+
Rilpivirine (900mg): 3mL IM
Continuation injections
* At month 5
* Every 2 months ( +/- 7 days)
Cabotegravir (600mg): 3mL IM
+
Rilpivirine (900mg): 3mL IM
How do you switch from monthly to q2monthly dosing
Monthly: Cabotegravir (400mg): 2mL IM + Rilpivirine (600mg): 2mL IM
(lower dose to ease in)
TO
Q2months: Cabotegravir (600mg): 3mL IM + Rilpivirine (900mg): 3mL IM
T/F FLAIR & ATLAS says CAB/RPV injections are non-inferior to PO ARV standard of care
True
T/F ATLAS 2M says Q2month injections are non-inferior to q monthly injections
True
How do you deal with missed doses for IM
For planned missed dosing (travel):
- PO bridging therapy (travelling for work)
