Mechanisms of Action
Describe the mechanism of action for abacavir.
NRTI; it is a nucleoside analog which is incorporated into the replicating strand of HIV but lacks the 3' OH group, thereby stopping DNA chain elongation.
Name the classes included in all first-line HIV treatment regimens.
Nucleoside Reverse Transcriptase Inhibitor (NRTI) and Integrase Strand Transfer Inhibitor (INSTI)
What is the class adverse effect of NRTIs?
Mitochondrial dysfunction, typically manifesting as lactic acidosis
Which antiretroviral has a sulfa moiety?
What is the only class of antiretrovirals that can comprise 2 of the 3 medications in a treatment regimen?
NRTIs. Don't double up on any other class of antiretrovirals (never 2 INSTIs, 2 PIs, etc).
Avoid lamivudine + emtricitabine (both cytosine analogs). Other NRTIs are different analogs so technically different MOAs.
How do darunavir and atazanavir inhibit HIV?
They are protease inhibitors, which inhibit the cleavage of viral polyproteins, leaving the newly replicated virus immature and inactive.
What two combination tablets are used for PrEP?
Truvada (TDF/emtricitabine)
Descovy (TAF/emtricitabine)
Which integrase inhibitor is most likely to cause CNS effects such as HA and insomnia?
Dolutegravir
Which 3 antiretrovirals can falsely elevated SCr by 0.1 to 0.4 mg/dL?
Dolutegravir
Cobicistat
Bictegravir
Which antiretrovirals need an acidic environment for absorption?
Rilpivirine and atazanavir. Separate antacids, monitor doses and timing of H2RAs, PPIs (or avoid altogether).
What is the mechanism of cobicistat?
COBI is a pharmacokinetic booster. It inhibits CYP3A enzymes, increasing the concentrations of darunavir, atazanavir, and elvitegravir (and many other medications).
What is the recommended quantity and refills for PrEP tablet regimens?
#30 with 2 refills or #90 with 0 refills
HIV antibodies take up to 84 days to appear so individuals on PrEP should be tested at this interval to prevent treatment of HIV with an inadequate regimen.
Compare etiology of SCr changes among TDF, TAF, BIC, DTG, and COBI.
TDF – proximal tubule dysfunction
TAF - fairly benign
BIC, DTG, COBI – false SCr elevation:
BIC blocks OCT2 & MATE1
DTG blocks OCT2
COBI blocks MATE1
Name the labs that should be performed prior to PrEP administration.
HIV (antigen/antibody)
HBV serology
SCr
pregnancy test if female
Screen for other STIs - syphilis, gonorrhea, chlamydia
Which class of antiretrovirals has the potential for significant chelation?
INSTIs - remember they look for a Mg or Mn binding site on integrase so will grab any cations too (Al, Mg, Ca, Fe most concerning).
How does maraviroc inhibit HIV?
It is a CCR5 inhibitor, one of the sites on the CD4 cell to which HIV can bind. A tropism is always performed to see if the HIV uses CCR5 (maraviroc would work) or CXCR4 (maraviroc would be ineffective).
What is the name (brand & generic) of the injectable PrEP regimen and how often is it administered?
Apretude (cabotegravir) administered q8 weeks. Labs should be done at this time as well.
What is the name of the test assessing a person's likelihood of having hypersensitivity with abacavir administration?
HLA-B*5701 (please memorize this for boards)
Which lab is monitored to assess response to antiretroviral therapy? What's the goal?
Which lab is monitored to assess immunologic status?
HIVRNA (viral load); goal nondetectable
CD4 (and CD4%)
What would you expect to happen with coadministration of a PI/PK booster and statins?
Increased statin concentrations. Atorvastatin and rosuvastatin preferred; start with lower dose and titrate slowly.
Describe the mechanism of bictegravir.
BIC binds to either a Mg or Mn cofactor on the integrase enzyme, preventing HIVDNA from being incorporated into host DNA.
Dovato (lamivudine/ dolutegravir) is dual therapy recommended for initial HIV treatment. Name 2 characteristics precluding its use.
Baseline viral load (HIVRNA) > 500,000 copies/mL
Coinfection with HBV
Which antiretroviral is most likely to cause indirect hyperbilirubinemia?
Atazanavir
What do you do if a patient states they take their antiretrovirals for HIV treatment daily but their viral load is elevated?
Perform a resistance test (genotype), question more about adherence.
What are the two safest inhaled corticosteroids for coadministration with PIs, ritonavir, or cobicistat?
Beclomethasone and flunisolide. Others have a risk of Cushing syndrome (even nasal sprays and orally inhaled corticosteroids).