Most are targeting the viral enzymes, specifically viral integrase, reverse transcriptase, and protease.
With combination therapy, HAART (highly active antriretroviral therapy)
Which parts of the HIV virus are most drugs that treat this condition targeting?
How is HIV treated?
Usually initiated when CD4 counts fall below 500 cells/mm� because the side effects can make the patients feel worse.
Pregnant patients, patients with a history of an AIDS defining illness, patients with HIV-associated nephropathy, and in patients with an
At what stage is therapy usually initiated for HIV+ patients and why?
Regardless of CD4 count, initiation of therapy is strongly recommended for which individuals?
They are analogs of native ribosides but lack a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase.
Most have activity of against both HIV-1 and HIV-2
It occurs between agents of the same analog cla
How do the antiretroviral nucleoside/nucleotide reverse transcriptase inhibitors work?
What strains of the HIV virus are most of these drugs effective against?
When does cross-resistance between agents occur?
What causes the majority of adverse effects with these drugs?
What other adverse effect should be considered with these drugs?
Tenofovir increases didanosine levels so co-administration of these drugs requires reduction in the dose of didanosine.
Tenofovir decreases concentrations of atazanavir but its levels can be boosted by co-adminstration with ritonavir.
No
What is the drug interaction between didanosine and tenofovir?
What is the drug interaction between atazanavir and tenofovir?
Are the NRTIs generally metabolized by cytochrome enzymes?
1. Nucleoside analog that lacks a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase
2. Used to treat HIV
3. Bone marrow suppression
Zidovudine (AZT)
1. Mechanism of action
2. Use
3. Adverse effects
1. Cytosine
2. Thymidine
3. Adenosine
4. Adenosine
5. Guanosine
6. Cytosine
7. Thymidine
What nucleoside are the following NRTIs analogs of?
1. Emtricitabine
2. Stavudine
3. Didanosine
4. Tenofovir
5. Abacavir
6. Lamivudine
7. Zidovudine
1. Nucleoside analog that inhibits ? and ? DNA polymerases
2. Used to treat HIV
3. Peripheral neuropathy and lactic acidosis as a result of its high affinity for mitochondrial DNA polymerase)
Stavudine
1. Mechanism of action
2. Use
3. Adverse effects
1. Nucleoside analog that lacks a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase
2. Used to treat HIV
3. Pancreatitis, especially in alcoholics and patients with hypertriglyceridemia (should not
Didanosine
1. Mechanism of action
2. Use
3. Adverse effects
1. Nucleoside analog that lacks a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase
2. Use to treat HIV (currently part of the recommended regimen for the treatment of HIV)
3. GI effects
It has a l
Tenofovir
1. Mechanism of action
2. Use
3. Adverse effects
What is important about this drugs pharmacokinetics?
This drug can be found in fixed dose cominations with what other drugs?
Tenofovir, emtircitabine, and efavirenz
What drugs are part of the preferred NRTIs in the currently recommended regimen for the treatment of HIV?
1. Nucleoside analog that lacks a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase
2. Used to treat HIV
3. Few significant AE
It does not affect mitochondrial DNA synthesis or bone marrow precurso
Lamivudine
1. Mechanism of action
2. Use
3. Adverse effects
What is unique about the adverse effects of this drug?
1. Nucleoside analog that lacks a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase
2. Use to treat HIV (currently part of the recommended regimen for the treatment of HIV)
3. Hyperpigmentation of
Emtricitabine
1. Mechanism of action
2. Use
3. Adverse effects
What is important about this drugs pharmacokinetics?
1. 1. Nucleoside analog that lacks a 3' OH group which leads to termination of DNA elongation and competitive inhibitor of reverse transcriptase
2. Use to treat HIV
3. 5% of patients develop a hypersensitivity reaction for which they should never be recha
Abacavir
1. Mechanism of action
2. Use
3. Adverse effects
They are non-competitive inhibitors of HIV-1 reverse transcriptase and cause inhibition of RNA and DNA dependent DNA polymerase.
No
Because the binding site is away from the active site a mutation in this site could result in resistance developing without
What is the mechanism of action of the non-nucleoside reverse transcriptase inhibitors?
Do these drugs require phosphorylation by cellular enzymes?
Why is resistance a problem with these drugs?
Is there cross resistance with these drugs?
1. HIV-1
2. HIV-1 and HIV-2
3. HIV-1 and HIV-2
4. HIV-1
5. HIV-1 and HIV-2
Are the following drugs useful in the treatment of HIV-1, HIV-2, or both?
1. NNRTIs (non-nucleoside reverse transcriptase inhibitors)
2. Protease inhibitors
3. NRTIs (nucleoside-analog reverse transcriptase inhibitors)
4. Enfuvirtide
5. Raltegravir
They lack effects on the host blood-forming elements and lack cross resistance with NRTIs)
They have cross-resistance with one another, are involved in drug interactions, and have a high incidence of hypersensitivity reactions.
vir
What are the advantages of the NNRTIs (non-nucleotide reverse transcriptase inhibitors)?
What are the disadvantages?
All these drugs have what in the the middle of their name?
They have a high incidence of hypersensitivity reactions (eg. rash) which can develop into Stevens-Johnson syndrome and they are all CYP3A4 substrates that can act as inducers, inhibitors, or both of CYP P450 enzymes.
What is a major disadvantage of the NNRTIs (non-nucleotide reverse transcriptase inhibitors)?
1. Non-competitive inhibitors of HIV-1 reverse transcriptase and cause inhibition of RNA and DNA dependent DNA polymerase
2. Used to treat HIV
3. Potential severe heptatoxicity and risk of hypersensitivity rash
Inducer of CYP3A4
Nevirapine
1. Mechanism of action
2. Use
3. Adverse effects
Is this an inducer or inhibitor of CYP3A4?
1. Non-competitive inhibitors of HIV-1 reverse transcriptase and cause inhibition of RNA and DNA dependent DNA polymerase
2. Use to treat HIV (currently part of the recommended regimen for the treatment of HIV)
3. Mostly CNS problems that typically resolv
Efavirenz
1. Mechanism of action
2. Use
3. Adverse effects
4.
What is important about this drugs pharmacokinetics?
Is this an inducer or inhibitor of CYP3A4?
Pregnancy Class?
1. Non-competitive inhibitors of HIV-1 reverse transcriptase and cause inhibition of RNA and DNA dependent DNA polymerase
2. Used to treat HIV in treatment-experienced patients
3. Risk of hypersensitivity rash and may cause elevations of tranaminase enzym
Etravirine
1. Mechanism of action
2. Use
3. Adverse effects
Is this an inducer or inhibitor of CYP3A4?
What about other CYP P450 enzymes?
1. Non-competitive inhibitors of HIV-1 reverse transcriptase and cause inhibition of RNA and DNA dependent DNA polymerase
2. Used to treat HIV but not as widely used as other NNRTIs due to its short half life
3. Development of a hypersensitivity rash and
Delaviradine
1. Mechanism of action
2. Use
3. Adverse effects
Is this an inducer or inhibitor of CYP3A4?
-navir (note: antiviral protease inhibitors end in -previr and most of the antiviral nucleoside/nucleotide analogs end in -vir)
They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse
All the antiretroviral protease inhibitors end in what?
What is the mechanism of action of the protease inhibitors?
Do these drugs require intracellular activation?
CYP3A4
Their levels will require monitoring when being administered with NNRTIs as these drugs are inducers/inhibitors of CYP enzymes including CYP3A4
Potent inhibitors (for the most part)
They are substrates for P-glycoprotein pumps.
Pharmacokinetics for protease inhibitors is important. What CYP enzyme are they a substrate for?
How will this affect its co-administration with other antiretroviral drugs?
Are these drugs inducers or inhibitors of CYP P450 enzymes?
What other interaction is important for these drugs bioavailability?
Parathesias, nausea, vomiting, diarrhea, disturbances in lipid metabolism, and fat redistribution and accumulation causing a cushingoid appearance.
Atazanavir
What are the common side effects of the protease inhibitors?
Which of the protease inhibitors has less side effects when compared to the other protease inhibitors?
A protease inhibitor (-navir)
A patient being treated for HIV presents with a cushingoid appearance including a buffalo hump, central obesity, breast enlargement, etc. What drug type is this patient likely being treated with that is causing this problem?
1. Protease inhibitor - They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse transcriptase, protease, and integrase. This prevents virus maturation and results in production of non
Atazanavir
1. Mechanism of action
2. Use
How do the adverse effects of this drug compare to the adverse effects of other protease inhibitors?
1. Protease inhibitor - They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse transcriptase, protease, and integrase. This prevents virus maturation and results in production of non
Darunavir
1. Mechanism of action
2. Use
Is this drug given with ritonavir?
1. Protease inhibitor - They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse transcriptase, protease, and integrase. This prevents virus maturation and results in production of non
Indinavir
1. Mechanism of action
2. Use
Is this drug given with ritonavir?
1. Protease inhibitor - They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse transcriptase, protease, and integrase. This prevents virus maturation and results in production of non
Lopinavir
1. Mechanism of action
2. Use
3. Contraindications
Is this drug given with ritonavir?
1. Protease inhibitor - They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse transcriptase, protease, and integrase. This prevents virus maturation and results in production of non
Nelfinavir
1. Mechanism of action
2. Use
Is this drug given with ritonavir?
1. A potent inhibitor of CYP3A4 which increases the levels of other protease inhibitors
2. Used to boost the levels of other protease inhibitors. Combined with atazanavir as the only once-daily preferred protease inhibitors
Ritonavir
1. Mechanism of action
2. Use
1. Protease inhibitor - They are reversible inhibitors of HIV aspartyl protease which is responsible for cleavage of the viral polyprotein into reverse transcriptase, protease, and integrase. This prevents virus maturation and results in production of non
Tipranavir
1. Mechanism of action
2. Use
Is this drug given with ritonavir?
1. HIV fusion inhibitor with a similar structure to gp41 which binds to the gp41 subunit of the viral envelope glycoprotein and prevents the ability of the virion to fuse with the cell membrane
2. Approved for treatment of HIV in treatment experienced adu
Enfurvitide
1. Mechanism of action
2. Use
Does this drug have activity against HIV-1, HIV-2, or both?
1. HIV entry inhibitor which binds to the CCR5 receptor which blocks HIV entry into cells
2. Used to treat HIVp
Metabolized by CYP3A4
The dose of this drug that is given to patients taking protease inhibitors (strong cytochrome inhibitors) needs to be red
Maraviroc
1. Mechanism of action
2. Use
This drug is metabolized by what cytochrome?
How does this affect its co-administration with other drugs?
1. Binds to integrase and causes inhibition of the final step of integration of the viral DNA into the host cell DNA
2. Approved for treatment of HIV in both treatment-naive and treatment-experienced patients
Both
It has very few drug interactions as a re
Raltegravir
1. Mechanism of action
2. Use
Is this drug used to treat HIV-1, HIV-2, or both?
This drugs metabolism is via UGT1A1-mediated glucuronidation. How does this affect its potential drug interactions?
Ritonavir and Atazanavir
What are the once daily preferred protease inhibitors for HIV patients?
IV
The entry and fusion inhibitors, maraviroc and enfuvirtide respectively, are both administered in what manner?
1. NNRTI & 2 NRTIs
2. A protease inhibitor (boosted with rionavir) & 2 NRTIs
3. INSTI (raltegravir) & 2 NRTIs
Tenofovir and emtricitabine
Ensure that the two agents given are not of the same nucleotide analog.
There are three current recommendations for HIV treatment in treatment-naive patients. What are they?
Which two NRTIs are used in each of the 3 possible treatments in treatment-na�ve patients?
When selecting nucleotide analogs, what should you avoid?
Ritonavir boosted lopinavir (twice daily) and zidovudine/lamivudine
Zidovudine started immediately after birth and administered for 6 weeks
What is the recommended HIV treatment for pregnant patients?
What is the current recommendation for an infant born to an HIV infected mother?
Strep. pneumoniae, HAV, HBV, and influenza. (inactive viruses)
Live vaccines like MMR and varicella.
What type of prophylactic vaccines should be given to HIV + patients?
What type of prophylactic vaccine should not be given to HIV + patients?
2 NRTIs
3 drug combination (NNRTI or protease inhibitor with 2 NRTIs)
Treat for one month starting within 1-2 hours after the needle stick.
Generally nothing but you can consider a 2 drug treatment regimen.
What are the recommended treatments for a less severe needle stick (solid needle & superficial injury) from an HIV+ patients?
What are the recommended treatments for a more severe needle stick (large-bore hollow needle and/or deep puncture) from an HIV+ patients?
How long should treatment continue?
What are the recommendations for needle sticks in patients with an unknown HIV status?