Antiretroviral Agents Flashcards
If you get stuck with a needle that has been injected in a patient positive for HIV, what is the chance that you will undergo seroconversion?
3/1,000 or 0.33%
What is considered the “backbone” of HIV antiretroviral therapy?
Two NRTIs and either (1) a protease inhibitor, (2) an NNRTI, or (3) an integrase inhibitor
Integrase inhibitors are the preferred first-line because they have few side effects and no documented resistance thus far.
Note: fusion inhibitors (enfurvitide) and CCR5 inhibitors are not recommended as first-line agents.
What is the only fusion inhibitor?
Enfuvirtide (which inhibits gp41)
Which class of HAART drugs is also active against HBV?
NRTIs (tenofovir)
Efavirenz has a declining use due to its psychiatric and teratogenic effects, but it is useful in what patient population?
Those being treated with rifampin for TB because efavirenz does not induce CYP as much as nevirapine.
Tenofovir should be avoided in which patients?
Those with osteoporosis or chronic kidney disease
What are INSTIs?
Integrase strand inhibitors
How is enfuvirtide administered?
Subcutaneous injection
Which regimens are least likely to induce resistance?
2 NRTIs + either boosted PI or INSTIs
Note: the best is 2 NRTIs and an INSTIs
The most absorbed form of tenofovir is __________.
TAF
Why are NRTIs toxic against mitochondrial?
They inhibit mitochondrial DNA polymerase.
Which class of HIV drugs is inhibited by PPIs?
NNRTIs (like rilpivirine or etravirine)
What mechanism allows resistance to maraviroc?
If an HIV strain develops X4 tropism –in which it uses predominantly CXCR4 rather than CCR5.
Why is maraviroc not in any combinations?
It is dosed twice daily, whereas most other antiretroviral drugs are once daily.
HIV never enters a state of true ______________.
latency
Resistance testing is recommended when ________________.
the patient is first seen and if their CD4 counts start to drop while on treatment
How do NRTIs work?
They mimic nucleotides but lack the 3’ hydroxyl group necessary for elongation of the genome (like Sanger sequencing).
How are the NRTIs administered?
Orally (most have good bioavailability)
NRTIs are excreted renally with the exception of ______________.
abacavir and zidovudine
The NNRTIs work by _________________.
inhibiting reverse transcriptase at a different, non-active site
Which class of antiretroviral drugs is usually the most resistant to mutations that confer resistance?
Protease inhibitors
What are some side effects of protease inhibitors?
Hyperlipidemia, hyperglycemia, and central adiposity (remember Guinevere with the raised candy and butter next to the fat horse with skinny legs)
Also, hepatotoxicity
Describe how HIV tropism changes with disease progression.
HIV typically starts out with R5 tropism –meaning it targets cells with CCR5 –then progresses to X4 tropism.
Tenofovir is contraindicated in patients with ______________.
osteoporosis and chronic kidney disease
What is “boosting”?
Adding ritonavir to combinations to increase the serum concentration (because ritonavir is a potent inhibitor of CYP)
Which of the entry-inhibiting drugs is hepatically metabolized?
Maraviroc
Enfuvirtide is metabolized by proteolysis so DDI with CYP is not a concern.
