HIV/AIDS Flashcards
Tx of Candida Infections in AIDS
-fluconazole
Fluconazole Dose for Candida Infections
100-200 mg daily until resolved then PRN
Primary Prophylaxis Drug for Pneumocystis Pneumonia
-TMP/SMX
Primary Prophylaxis Alternatives for Pneumocystis Pneumonia
- clindamycin + pyrimethamine
- atovaquone
- pentamidine
Long Term Management of Pneumocystis Pneumonia
ongoing secondary prophylaxis
Primary Prophylaxis for Toxoplasmosis gondii
-TMP/SMX
Treatment of Toxoplasmosis gondii
- sulfadiazine: wt based dose qid
- pyrimethaine: high loading dose then 50-75 mg daily
Long Term Management of Toxoplasmosis
-secondary prophylaxis and ongoing suppressive therapy
Primary Prophylaxis for Cryptococcal Infections
primary prophylaxis not indicated
Cryptococcus Treatment
-liposomal amphotericin
AEs of Amphotericin
- HoTN
- fever/rigors
- anemias
- low Mg, low K
Amphotericin Toxicities
- renal dysfunction
- marrow suppression
Long Term Management of Cryptococcus
- consolidation: fluconazole 400 mg daily x8 wks
- secondary prophylaxis: fluconazole 1 year
Cytomegalovirus Prophylaxis
-not used b/c of therapy toxicity
Cytomegalovirus Treatment
-ganciclovir or valganciclovir
Mycobacterium Avium Intercellulare Primary Prophylaxis
azithromycin 1200 mg/wk
Treatment of Mycobacterium Avium Intercellulare
-azithromycin 600 mg/day PO
-plus ethambutol
+/- rifampin or rifabutin
Primary Goals of Opportunistic Infection Therapy
- reduce HIV associated morbidity
- prolong the duration and quality of survival
- preserve and restore immunologic function
- maximally and durably suppress HIV
- prevent future transmissions
Drawbacks of Early Therapy
- unknown long term ARV-related toxicities
- life long tx and pill fatigue = non-adherence
- costs to the pt and the healthcare system
What conditions might favor earlier treatment?
- pregnancy
- HIV associated nephropathy
- HBV-HIV or HCV-HIV co-infection
- acute or recent infx
- HIV associated dementia
- AIDS defining condition
- lower CD4 <200
- acute opportunistic infxs
When should deferral of therapy be considered?
- significant adherence barriers (clinical, personal, psychosocial)
- serious comorbidity: incurable CA, end stage liver dz, life expectancy shorter than time for QOL benefits
- long term non-progressor
- elite controller
MOA NRTIs
- drugs compete with nucleotides
- terminate viral DNA chain
- block HIV replication
How are NRTIs administered?
PO
What is the bioavailability of NRTIs?
- variable
- not affected by food
How are NRTIs excreted?
renally cleared
MOA of N-NRTIs
- binds non-competitively adjacent to active site
- prevents HIV RNA conversion to proviral DNA
How are N-NRTIs administered?
PO
What is the bioavailability of N-NRTIs?
- very good
- increased with food
How are N-NRTIs metabolized?
- extensive hepatic metabolism
- many drug-drug interactions due to CYP450
MOA of Protease Inhibitors
-blocks process that stimulates viral maturation
How are PIs administered?
PO
How are PIs metabolized?
- extensive hepatic metabolism
- many drug-drug interactions due to CYP450
What do all preferred HIV treatment regimens have?
TWO NRTIs
Emtricitabine-Tenofovir (Truvada) AEs
- fatigue
- cramps
- elevated creatine kinase
- hypophosphatemia
Emtricitabine-Tenofovir (Truvada) Toxicities
- renal insufficiency (Fanconi’s syndrome)
- changes in bone density
Emtricitabine-Tenofovir (Truvada) Lab Follow-up
- renal function
- DEXA scan
Lamivudine-Abacavir (Epzicom) Toxicities
- hypersensitivity reaction
- may have additive effects if combined w/ other meds with overlapping AEs
Lamivudine-Abacavir (Epzicom) Pre-treatment Lab and Why It Is Done
- HLA B5701
- if positive, 50-50 chance for severe hypersensitivity reaction
Lamivudine-Abacavir (Epzicom) Lab Follow-up
- hepatic function
- renal function
NNRTI Efavirenz (Sustiva) AEs
- vivid dreams, insomnia, depression
- rash
- increased LFTs
- dizziness
- high triglycerides
NNRTI Efavirenz (Sustiva) Toxicities
- hepatitis
- hepatic necrosis
NNRTI Efavirenz (Sustiva) Metabolism
-inducer/inhibitor of CYP450
When should NNRTI Efavirenz (Sustiva) be taken?
-take on empty stomach qHS to reduce AEs
NNRTI Rilpivirine (Edurant) AEs
- depression
- insomnia
- HA
- rash
NNRTI Rilpivirine (Edurant) Toxicities
- QT prolongation
- dyslipidemia
- increased LFTs
NNRTI Rilpivirine (Edurant) Metabolism
hepatic via CYP3A4
How should NNRTI Rilpivirine (Edurant) be taken?
-with food b/c it needs an acidic environment to be absorbed
What is contraindicated with NNRTI Rilpivirine (Edurant)?
taking PPIs (can cause therapeutic failure)
INSTI Raltegravir (Isentress) AEs
- elevated BGs, including lipase and ALT
- myopathy
INSTI Raltegravir (Isentress) Lab Follow-up
- blood glucose
- CK
- LFTs
How is INSTI Raltegravir (Isentress) dosed?
- PO tablet
- must be BID (2 pills @ once may cause therapeutic failure)
INSTI Elvitegravir (Vitekta) AEs
- well tolerated
- N/D
INSTI Elvitegravir (Vitekta) Lab Follow-up
fasting lipid panel
How should INSTI Elvitegravir (Vitekta) be taken?
- oral tablet once daily
- WITH food and a PK booster (blocks metabolism of elvitegravir so it stays in body longer)
What is a PK booster (eg Cobicistat/Tybost)?
- pharmacokinetic enhancer: blocks metabolism of a drug so it stays in body longer
- NO antiviral properties
Cobicistat/Tybost AEs
- nausea, loose stool
- elevated SCr, cholesterol and triglyceride
INSTI Dolutegravir (Tivicay) AEs
- well tolerated
- HA
- hyperglycemia
- elevated lipase and transaminases
INSTI Dolutegravir (Tivicay) Lab Follow-up
- blood glucose (HbA1c)
- CK
How should INSTI Dolutegravir (Tivicay) be taken?
- PO once daily
- may take w/o food
- does not require a PK booster
PI Atazanavir (Reyataz) AEs
- rash
- hyperbilirubinemia
PI Atazanavir (Reyataz) Toxic Effects
- AV block
- nephrolithiasis
- elevated transaminases
PI Atazanavir (Reyataz) Lab Follow-up
- fractionated bilirubin
- LFTs
How should PI Atazanavir (Reyataz) be taken?
- once daily
- take w/ food (needs acidic enviro to be absorbed)
- needs PK booster
PK Booster Ritonavir (Norvir) AEs
- HA
- N/V/D
- taste perversion
- elevated CK
- hyperglycemia
- elevated LFTs
- hyperlipidemia
PK Booster Ritonavir (Norvir) Lab Follow-up
- LFTs
- fasting lipids and BGs
- possible EKG
PI Darunavir (Prezista) AEs
- rash (SJS)
- diarrhea
- hypercholesterolemia/TGs
- hyperglycemia
PI Darunavir (Prezista) Lab Follow-up
- LFTs
- fasting lipid panel
- BGs
How should PI Darunavir (Prezista) be taken?
- qday or BID
- take with food
- always take with PK booster
Are there major drug interactions with NRTIs?
- not really
- all but one (abacavir) are renally cleared)
- dose adjust all except abacavir for renal impairment/failure
Are there major drug interactions with N-NRTIs?
- YES!
- varying CYP450 influences (+ or -)
What drugs are contraindicated with N-NRTIs?
- dexamethasone
- PPIs
- certain anticonvulsants (phenytoin, CBZ, etc)
Are there major drug interactions with PIs?
- YES
- all PIs have extensive CYP450 interactions
- LOTS of contraindications with commonly used medications
What drugs are contraindicated with PIs?
- alprazolam, triazolam
- simvastatin, lovastatin
- all ergot alkaloids
- amiodarone, propafenone
- salmeterol
- caution with fluticasone, ethinyl estradiol, warfarin
What lab monitoring should be done with ARVTx?
- absolute CD4 count should be stable or improved
- viral load should decrease
Based on lab values, when is tx considered a failure?
VL > 400 copies/mL @ 24 weeks
OR VL > 48-75/mL @ 48 weeks
What factors can contribute to ARV resistance?
- improper administration
- improper absorption (delayed or malabsorption)
- improper storage
- missing doses
- wide variability or inconsistent dosing schedule
