ID exam 5 everything *

Metabolizer types

Ultrarapid=high rate metabolism; extensive/normal=normal metabolism; intermediate=30-70% lower metabolism; poor=significantly low metabolism

HLA genes

Help immune system recognize and respond to foreign substances

Abacavir class

NRTI reverse transcriptase inhibitor

Abacavir HLA test

Test HLA-B5701 before starting abacavir

Abacavir hypersensitivity

Life-threatening hypersensitivity reaction within 6 weeks

Highest HLA-B5701 carrier frequency

Southwest Asian patients

Lowest HLA-B5701 carrier frequency

African patients

Atazanavir PGx gene

UGT1A1

UGT1A1 function

Removes bilirubin

UGT1A1 mutation effect

Jaundice from high bilirubin

UGT1A1 safe alleles

C/C or C/T

UGT1A1 high-risk allele

T/T

Voriconazole metabolism

CYP2C19

Voriconazole ultrarapid metabolizer

Need higher dose

Voriconazole poor metabolizer

Higher adverse effect risk and need lower dose

COVID-19 ACE2 PGx

GG genotype or G allele increases severe disease/fatality risk

MT-RNR1 mutation effect

Allows aminoglycosides to bind mitochondria and cause cellular damage

MT-RNR1 variant

A>G

MT-RNR1 aminoglycoside risk

Hearing loss

G6PD deficiency function

Enzyme protects RBCs from oxidative stress

G6PD deficiency result

Oxidative stress and hemolytic anemia

G6PD deficiency populations

Males, Africa, Mediterranean, Middle East, Southeast Asia

Dapsone in G6PD deficiency

Can cause hemolytic anemia

Dapsone use

PCP prophylaxis in HIV

Abacavir FDA/CPIC recommendation

Do not use if HLA-B5701 carrier

Atazanavir CPIC recommendation

Avoid if markedly decreased UGT1A1 activity

MT-RNR1 CPIC recommendation

Do not use aminoglycosides if A>G variant

Rapid POCT importance for MT-RNR1

Needed for neonatal sepsis

High-risk drugs in G6PD deficiency

Dapsone, primaquine, rasburicase, tafenoquine

Low-risk drugs in G6PD deficiency

Amoxicillin, penicillins, fluoroquinolones, azithromycin, macrolides, cephalosporins

Medium-risk drugs in G6PD deficiency

Nitrofurantoin, chloroquine, Bactrim

Phenoconversion

Environmental factors causing different phenotype

Phenoconversion cause in HIV

Inflammation causing CYP downregulation/increased cytokines

HIV extensive metabolizer phenoconversion

May phenotypically appear as poor metabolizer

Rapid PGx testing method

PCR amplification to detect A>G variant

Purpose of rapid PGx testing in neonatal sepsis

Determine if aminoglycosides can be used

HIV cause

Retrovirus

HIV discovered

1981

HIV US epidemiology

1.2 million infected; 160,000 unaware

Global HIV epidemiology

40 million infected

HIV transmission fluids

Blood, semen, breast milk, vaginal secretions

HIV transmission methods

Sex, needles, birth

HIV transmission requirement

Detectable viral load

Ways to reduce HIV transmission

Limit sexual partners, know status, condoms, injection drug services

PrEP candidates

MSM, discordant couples, PWID

PEP candidates

Healthcare workers, sexual assault, needle sharing

Perinatal HIV prevention

Maternal testing and antiretrovirals during pregnancy

Primary HIV symptoms

Fever, lethargy, myalgias, rash, headache

Untreated HIV progression to AIDS

10-11 years

CD4 cells

Lymphocytes infected by HIV

CD4 normal range

600-1200

CD4 <200

High opportunistic infection risk

Viral load definition

Copies of HIV RNA/mL blood

Goal HIV viral load

Undetectable <50

NRTI class adverse effects

Lactic acidosis and hepatic steatosis

NRTI lactic acidosis/hepatic steatosis management

Switch therapy

Emtricitabine combo products

Truvada, Atripla, Complera

Lamivudine characteristics

Well tolerated

Lamivudine combo products

Dovato, Triumeq

Lamivudine rare ADE

Alopecia

Tenofovir AF

Better renal/bone safety; worse lipids

Tenofovir DF

Monitor renal impairment

Zidovudine use

Prevent perinatal transmission

NNRTI class effects

Rash, increased LFTs, DDIs

Efavirenz pearls

Rarely used; avoid in pregnancy and depression

Etravirine

High barrier to resistance but many DDIs

Nevirapine major ADEs

Serious rash and hepatotoxicity

Avoid nevirapine in women

CD4 >250

Avoid nevirapine in men

CD4 >400

Nevirapine liver monitoring

Baseline, weeks 2,4,8,12,16, then every 3 months

Rilpivirine meal requirement

Take with fat-containing meal

Rilpivirine acid suppression interaction

Avoid PPIs; separate H2 blockers by 12 hours

Do not start rilpivirine if viral load

100,000

PI class effects

GI effects, hyperlipidemia, lipodystrophy, hyperglycemia, bone density changes, bleeding risk, DDIs

PI metabolism

CYP3A4

Avoid PIs in

Significant cardiac risk factors

Egrifta use

Treat lipodystrophy

Egrifta adverse effects

Worsened glucose control and injection site reactions

Atazanavir cardiovascular effects

Lowest among PIs

Atazanavir absorption

Needs acid

Darunavir administration

Take with food

Darunavir ADEs

GI effects, rash, sulfonamide allergy

Fosamprenavir ADE

Rash and sulfa allergy

INSTI mechanism

Blocks integrase so HIV DNA cannot insert

INSTI adverse effects

Insomnia, depression, suicidal ideation, weight gain, increased SCr

Elvitegravir administration

Take with food and away from antacids

Raltegravir drawback

BID dosing

Dolutegravir administration

Take away from divalent cations/laxatives

Bictegravir availability

Only in combo products

Bictegravir interaction

Take away from aluminum/magnesium

Bictegravir SCr effect

Small increase without reducing GFR

Cabotegravir boxed warning

Drug resistance if undiagnosed HIV

Cabotegravir requirement

Test for HIV first

Cabotegravir injectable use

For HIV RNA <50 copies/mL

Ritonavir role

PK enhancer only; not monotherapy

Enfuvirtide route

SQ

Enfuvirtide use

Adherence and resistance issues

Enfuvirtide counseling

Rotate injection sites

Enfuvirtide pneumonia risk

Increased bacterial pneumonia risk

Maraviroc mechanism

Binds CCR5 on CD4 cells