The Role of Pharmacogenomics in Management of HIV Infection- Spooner

What are important counseling points for ART?

Strict adherence to medication dosing and office visits, encouraging consistent use of 1 pharmacy, performing a profile review at initiation and every refill, ensure Pt is comfortable with disclosing OTC rxs

what medication do we used for pediatric patients weighing under 40kg

efavirenz

What is considered a high viral loa

>100,000 copies/mL

What is first line treatment for HIV?

INSTI + 2 NRTIs

What products contain abacavir?

Ziagen, Epzicom, Trizivir, Triumeq

what are the two roles of genomic information in ART

identifying ARV resistance mutation, identify host cell genome variants that modulate response and adverse effects (not done very frequently)

what kind of ART is abacavir

NRTI

abacavir clinical pearls

increased risk of MI

no renal dose adjustment

hypersensitivity reaction

when do hypersensitivty reactions occur with abacavir

within the first 6 weeks of treatment if genetic prescreening is not performed

what symptoms appear with hypersensivity reaction (at least 2)

fever, rash, N/V/ abdominal pain, fatigue, cough, dyspnea

what do you need to immediately do if a patient has a hypersensitive reaction

immediately discontinue and never rechallenge, can lead to life threatening reactiong

what patient populations have HLA-B*57:01 allele

european, african, asian (japenese does not have any)

Which regimens are not recommended for rapid ART initiation?

Which regimens are not recommended for rapid ART initiation?

in treatment naive individuals when do you need to screen patients

prior to initiating therapy or prior to considering abacavir treatment

true or false HLA-B*57:01 status has no effects on drugs PK/PD

true

if you are HLA-B*57:01 positive

do not initiate abacavir because of increased risk of reactions, mark in allergy section, use alternative NRTI

if you are HLA-B*57:01 negative

may start abacavir, provide counseling and education for reactions

true or false we do patch testing for HLA-B* 57:01

false

what kind of ART is efavirenz

NNRTI

adverse effects of efavirenz

disordered sleep, horrible dreams, psychosis, depression, suicidal ideation, occurs in first few days- 6 weeks abused in south africa for these effects

why was efavirenz removed from the "use in most situations" list

due to neurologic adverse effects/ discontinuation/ and drug interactions

what is efavirenz metabolized by

CYP2B6, autoinducer with chronic dosing it enhances its own metabolism

what can you use with efavirenz that you can not use with other ART

rifampin

what population is efavirenz recommended for

pregnant women and women who wish to become pregnant

CYP2B6 poor metabolizer phenotype

reduced clearance of efavirenz, increased toxicity, increased risk of discontinuation

What are the dosing recommendations of efavirenz for ultra-rapid, rapid, and normal metabolizers of CYP2B6?

600mg/ day

What are the dosing recommendations of efavirenz for poor metabolizers of CYP2B6?

400 or 200mg/ day

What are the dosing recommendations of efavirenz for intermediate metabolizers of CYP2B6?

400mg/ day

symfi-lo contains

efavirenz with TDF/ lamivudine

what are the disadvantages of precision dose reduction with efavirenz

genotyping required, multiple copays, potential for sub-therapeutic EFV concentration and virologic failure, drug interactions

what kind of drug is atazanavir

protease inhibitor

atazanavir as a single agent

reyataz

atazanavir with COBI

evotaz

what does atazanavir require for doing

boosting with RTV or COBI

what is the adverse effect of atazanavir

indirect hyperbilirubinemia from inhibition of UGT1A1 mediated glucuronidation of bilirubin which increases plasma concentration of indirect bilirubin

who is at highest risk for bilirubin related discontinuation

patients who carry 2 UGT1A1 decreased function alleles

extensive metabolizer or intermediate metabolizer of UGT1A1

can use atazanavir

poor metabolizer of UGT1A1

high risk of bilirubin related discontinuation do not use atazanavir