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
ARV agents with highest genetic barriers to resistance
(PIs, etravirine, and dolutegravir). These medications have a high genetic barrier to resistance.
Transmitted resistance prevalence in naive patients and recommendations for testing before initiation
Transmitted resistance prevalence: NNRTIs > NRTIs > PIs > INSTIs (c) Recommended before treatment initiation to guide initial ART regimen selection (d) In acute HIV infection and in pregnancy, treatment should be initiated empirically and modified as needed after results.
HIV genotypic resistance testing timing
Test should be done while the patient is receiving treatment or within 4 weeks of ART discontinuation (ability to detect resistance during selective pressure). (c) Previous resistance reports should be evaluated as resistance is archived in HIV reser- voirs; absence of resistance to ARV medications on subsequent resistance tests is mislead- ing because resistance will reemerge under selective drug pressure.
Monitoring and goals for HIV VL after initiation of ART
HIV viral load (suppression is less than 20–75 copies/mL; below lower limits of detection): 2–8 weeks after treatment initiation, every 3–4 months for 2 years of ART; then every 6 months with persistent virologic suppression and CD4 greater than 300 cells/
Monitoring for CD4 count after ART
mm3 b. CD4 count i. Immunologic response to ART and when OI prophylaxis may be discontinued ii. Every 3–6 months for 2 years of ART; then yearly with suppressed viral load and CD4 greater than 300 cells/mm3
HIV regimens for MOST patients
DTG + TAF/FTC DTG + TDF/FTC DTG/ABC/3TC EVG/c/TAF/FTC EVG/c/TDF/FTC RAL + TAF/FTC RAL + TDF/FTC
Alternative treatment regimens for HIV
EFV/TDF/FTC EFV+ TAF/FTC RPV/TDF/FTC (HIV <200K & CD4>200) RPV/TAF/FTC (HIV <200K & CD4>200) DRV/r + TDF/FTC DRV/r + TAF/FTC DRV/c + TDF/FTC DRV/c + TAF/FTC ATV/c + TAF/FTC ATV/c + TDF/FTC ATV/r + TAF/FTC ATV/r + TDF/FTC DRV/r + ABC/3TC DRV/c + ABC/3TC ATV/c + ABC/3TC ATV/r + ABC/3TC RAL + ABC/3TC DRV/r + RAL If no TDF/TAF/ABC LPR/r + 3TC if no TDF/TAF/ABC
ARVs to avoid in cardiac patients
ARV medications that may worsen cardiac risks i. Abacavir should be avoided or used with caution in patients with high CV risk. ii. Lopinavir/ritonavir and darunavir/ritonavir have increased CV risk in some studies
PEP for infants born to HIV-positive mothers
the greatest risk of perinatal
transmission is during delivery
(b) Zidovudine should be initiated within 6–12 hours of delivery and continued for 4–6 weeks, depending on the infant’s HIV risk. (c) Infants should receive cART prophylaxis regimen in the following high-risk situations: (1) HIV-infected mother did not receive ART during pregnancy or intrapartum (2) HIV-infected mother only received intrapartum ART (3) HIV-infected mother did not have viral suppression near delivery on prescribed therapy (4) Maternal HIV status is unknown at the time of delive
HIV/HBV co-infection management
HBV/HIV-coinfected patients should be treated with two HBV-active agents
HIV-HCV coinfection management
Treating HIV and HCV concurrently: (1) ART should be initiated in all coinfected patients for immunologic improvement and for reducing HIV-related inflammation and immune activation.
HBV/HCV coinfection management in HIV-positive patients
Patients should be tested for HBV prior to HCV therapy and those with chronic HBV infection should be treated with NRTIs active against both HBV and HIV prior to starting HCV therapy to prevent reactivation of HBV infection
NRTI interactions with HCV DAAs
Patients should be tested for HBV prior to HCV therapy and those with chronic HBV infection should be treated with NRTIs active against both HBV and HIV prior to starting HCV therapy to prevent reactivation of HBV infection
IRIS incidence in CMV/Crypto/TB/HSV
Estimated incidence (a) Cytomegalovirus retinitis – CMV (38%) (b) Cryptococcal meningitis (30%) (c) Mycobacterium tuberculosis (16%) (d) Herpes zoster (12%)
iii. Estimated mortality incidence (a) Cryptococcal meningitis (21%) (b) M. tuberculosis (3%)
Management of IRIS
Mild to moderate-severe IRIS symptoms: Nonsteroidal anti-inflammatory drug (NSAID) therapy – Not recommended in cryptococcal meningitis
Unremitting symptoms on NSAID therapy: Brief course of glucocorticosteroids (e.g., predni- sone for 2–8 weeks; duration depending on OI).
Timing of ART initiation relative to OI treatment for PJP/MAC/Crypto/to our
PJP - WITHIN 2 weeks
MAC - AFTER 2 weeks of MAC tx
Crypto - AFTER 2-10 weeks of crypto tax
Todo - WITHIN 2 weeks of toxo tx
Preferred RFB dosing with 3a4 interaction
(1) Rifabutin (A) PIs – Rifabutin daily dosing at a reduced dose (150 mg); three-times-weekly dos- ing no longer recommended
Clarithro - PI interaction
(2) Clarithromycin – Increased clarithromycin concentrations but no dose adjustments recommended except those with renal impairment;
RFB-TAF interaction
Tenofovir alafenamide (P-glycoprotein substrate): Rifabutin: Reduced tenofovir alafenam- ide concentrations; coadministration not recommended
Regimens for toxo encephalitis
1st-line: pyrimethamine/sulfadiazine/leucovorin
Alternative:
pyrimethamine/clindamycin/leucovorin (must add PCP ppx)
TMP/SMX
Atovaquone + (pyrimethamine or sulfadiazine)
Azithromycin + pyrimethamine/leucovorin
Thx for at least 6 weeks
Initiating ART in TB
Initiation of ART: (a) CD4 count less than 50 cells/mm3 : ART should be initiated within first 2 weeks of TB treatment
CD4 count of 50 cells/mm3 or greater: ART should be initiated 8–12 weeks after initiation of TB treatment.
TB meningitis: ART should be initiated at least 8 weeks after initiating TB treatment, regardless of CD4 count.
Monitoring during PrEP
HIV testing should be done at baseline and every 3 months, and renal monitoring should be done every 6 months.
PEP in HCWs
PEP: Exposed health care workers should receive a three-drug regimen for 4 weeks within 72 hours of exposure.
1 tenofovir/emtricitabine tablet once daily and b. 1 raltegravir tablet twice daily
Meningococcal vaccination in HIV
Two-dose series of meningococcal ACWY conjugate vaccine; revaccinate q5 years
Pneumococcal vaccination in HIV
Unvaccinated: PCV13 then PPSV 8 weeks later
Prior PPSV: PCV13 at least 1 year after PPSV
PEP for HCWs if source HIV status unknown
HIV status of source patient is unknown: a. Rapid HIV testing of the source patient should be used to guide the use of PEP, and PEP should not be delayed awaiting results. b. If the test is negative, PEP may be discontinued, and no further testing is needed. c. Concerns for false-negative results related to seroconversion should not direct therapy unless acute retroviral syndrome is suspected.
