Treatment of HIV (Dr. Pogue)
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What are the 5 treatment goals for HIV?
- reduce HIV-related morbidity and prolong survival
- improve quality of life
- restore and preserve immunologic function
- maximally and durably suppress viral load
- prevent vertival transmission
True or false. Antiretroviral regimens should contain at least 2, preferably 3 active drugs from multiple drug classes.
When should you treat HIV (5 instances)?
- In patients with AIDS defining illnesses
- All HIV infected patients
- Pregnant women
- Patients with HIV-associated nephropathy
- Patients co-infected with HBV and undergoing treatment
True or false. You should co-treat HIV with HAV.
False, you should co-treat HIV with HBV.
What are the 6 different classes of drugs that are used in the treatment of HIV?
- nucleosides/nucleotide reverse transcriptase inhibitors (NRTIs)
- nonnucleoside reverse transcriptase inhibitors (NNRTIs)
- protease inhibitors (PIs)
- fusion inhibitors (FIs)
- CCR5 antagonists
- integrase inhibitor
Which 2 classes of HIV drugs are used in resistant patients?
- fusion inhibitors
- CCR5 antagonists
What is the general regimen for HIV treatment?
2 NRTIs plus 1 NNRTI, a "boosted" PI, or raltegravir
What is the preferred NNRTI used in HIV treatment regimen? When should you use caution in administering this drug?
Efavirenz; in pregnancy (teratogenic)
What is the mechanism of action for efavirenz (and other NNRTIs)? Why are these drugs considered to be detrimental?
non-competitive inhibitor of reverse transcriptase; long half-life, teratogenic, CNS symptoms
What HIV drug can be used in pregnant patients? What is the most significant ADE?
What are the advantages and disadvantages of NNRTI based regimens?
- Advantagescan save PIs for duture use
- long half-lives (for less compliant patients)
What does a PI based regimen consist of? What is the mechanism of action?
1 PI with a NRTI; binds to and inhibits HIV protease
What the 3 preferred PI based regimen treatments?
- atazanavir with ritonavir
- darunavir with ritonavir
Why should you avoid using PIs in diabetic patients? and what is the main drug interaction?
Main side effect is dyslipidemia; inhibitor and substrates of CYP3A4
What are the advantages and disadvantages of PI based regimens?
- Barrier against resistance
- metabolic complications
- GI side effects
- CYP3A4 issues
What does a NRTI based regimen consist of? What is the mechanism of action? Adverse effects?
"backbone" of all HAART regimens, tenofovir/emtricitabine; chain terminator which inhibit reverse transcriptase; lactic acidosis and hepatic steatosis
What is the specific adverse effect of Abacavir (NRTI)?
hypersensitivity, involves HLA-B*5701 allele
Which NRTI is the most well tolerated in treating HIV?
Which NRTI causes bone marrow suppression?
What is the most common NRTI combo product?
Combivir (lamivudine with zidovudine)
Which PI is most commonly used to treat HIV?
What is the mechanism of action for fusion inhibitors (FIs)? Route of administration? Adverse effects?
inhibits viral entry into cell; SubQ; injection site reactions, pneumonia, hypersensitivity
What is the mechanism of action for Mirovac? Side effects? Drug interactions?
CCR5 antagonist; URI, dizziness, fever; CYP3A4 substrate
What is the mechanism of action for Raltegravir? Side effects? Drug interactions?
blocks active site of HIV integrase; well-tolerated, may have CPK elevations, rhabdomyolysis; statins
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