HIV Flashcards
CDC recommendations for HIV screening
CDC: i. Opt-out screening for all patients age 13–64 one time in all health care settings during routine care ii. All people with a diagnosis of, and seeking evaluation of or treatment for, a sexually transmit- ted disease, TB, or hepatitis should be screened for HIV infection. iii. Annual HIV testing is recommended for people with the following risk factors: men who have sex with men (MSM), sex with HIV partner, intravenous drug use/shared needles, and sex workers; MSM and bisexual men may benefit from testing every 3–6 months
Seroconversion window in HIV
Seroconversion window a. Time between HIV infection and detection of HIV antibodies b. Time to form antibodies: Around 20–25 days after HIV infection c. HIV RNA or p24 antigen is present during acute infection (10–20 days after infection)
HIV ARV transporter renal transporter interactions
Tenofovir is actively secreted by OAT1 and MRP2. (2) Inhibition of OCT2 (e.g., by dolutegravir or rilpivirine) or MATE1 (e.g., by cobicistat) (A) Dolutegravir and cobicistat inhibit tubular secretion of creatinine without affect- ing glomerular filtration rate (GFR) (increasing SCr concentrations). (B) Reduces metformin elimination (maximal daily dose with dolutegravir is 1000 mg) Dolutegravir inhibits the renal organic cation transporter (OCT2), increasing metformin concentrations by 2-fold.
(3) Inhibition of P-glycoprotein by PIs (especially ritonavir)
Advantages of TAF vs TDF
Advantages of tenofovir alafenamide over tenofovir disoproxil fumarate: (1) Less bone mineral density (BMD) loss (2) Significantly fewer GFR changes from baseline and proteinuria; no reports of proxi- mal renal tubulopathy to date (3) GFR is improved when changing from tenofovir disoproxil fumarate to tenofovir alafenamide. (4) Renal dose adjustments: Tenofovir disoproxil fumarate should be avoided in patients with a creatinine clearance (CrCl) less than 60 mL/minute/1.73 m2 at baseline or dose adjusted with a CrCl less than 50 mL/minute/1.73 m2 , whereas tenofovir alafenamide is approved to 15 mL/minute/1.73 m2 .
P450 interaction profile of NNRTIs
All are substrates of CYP3A4; all but rilpivirine induce CYP3A4; etravir- ine inhibits 2C9, 2C19, and P-glycoprotein.
NNRTI rash characteristics
Class effect; more common with older agents (nevirapine and efavirenz); cases of
Stevens-Johnson syndrome and toxic epidermal necrolysis; mild to moderate rashes gen-
erally resolve with continued treatment; if rash with systemic symptoms, NNRTIs should
be discontinue
NNRTI cardiovascular effects
Efavirenz may increase TG and LDL; other NNRTIs do not adversely affect the lipid panel; fat redistribution (lipohypertrophy) occurs with efavirenz regimens.
PI lipid effects
all boosted PIs increase LDL and TG with newer agents (darunavir and ataza- navir) having less hypertriglyceridemia; fat redistribution (lipohypertrophy) reported with PI regimens
PIs and renal effects
Renal effects: Atazanavir and lopinavir/ritonavir have a greater incidence of chronic kidney disease; kidney stones have formed on atazanavir and indinavir.
INSTI metabolism/transport
Pharmacokinetics: All are substrates of UGT1A1; elvitegravir is also a substrate of CYP3A4 and is boosted with cobicistat.
INSTI associated with increased LDL and TG
Dyslipidemia: Increased LDL and TG (elvitegravir/cobicistat)
Musculoskeletal adverse effects with INSTI
Myopathy: Rare cases of increased creatine phosphokinase, weakness, rhabdomyolysis with raltegravir
Renal effects of INSTIs
Changes in SCr (a) Cobicistat and dolutegravir typically increase SCr less than 0.2 mg/dL from baseline within 4 weeks of initiating therapy. (b) Patients receiving cobicistat with SCr changes greater than 0.4 mg/dL should be mon- itored closely and evaluated for renal tubulopathy associated with tenofovir disoproxil fumarate.
Modern ART regimens that should be given with food (for absorption/tolerability)
Require food for absorption and/or tolerability: PIs, NNRTIs (etravirine; rilpivirine – high- calorie meal: 400+ calories), INSTI (elvitegravir)
Modern ARVs requiring empty stomach for absorption/tolerability
Empty stomach for absorption or tolerability: NRTI (didanosine), NNRTI (efavirenz
NNRTI interactions with antiplatelet/anticoagulants
(etravirine and efavirenz) inhibit CYP 2C9 and 2C19 metabolism of other drugs and may reduce the bioactivation of clopidogrel (more evidence with etravirine); INR (inter- national normalized ratio) should be closely monitored while on concomitant warfarin therapy
PPI - ART interactions
Proton pump inhibitors are contraindicated with rilpivirine (absorption)
Proton pump inhibitors interact with atazanavir absorption