HIV Therapy Flashcards
Does ART cure HIV?
NO - it only keeps the viral load low
What is the major target cell of HIV?
CD4+ T cells
What is the normal CD4 T cell count?
800-1500 cells/mm3
At what level of CD4 cells are patients at increased risk for infections?
Less than 500 cells/mm3
What is used to determine the viral load in HIV?
PCR-based load assessment testing
When do you start ART?
ART is recommended for all HIV-infected individuals, regardless of CD4 T lymphocyte cell count, to reduce the morbidity and mortality associated with HIV infection
Where is HIV-2 endemic?
West Africa
What class are these drugs?
- Abacavir
- Didanosine
- Emtricitabine
- Lamivudine
- Stavudine
- Tenofovir
- Zidovudine
Nucleoside/Nucleotide RT Inhibitors
NRTI MOA
They are nucleotide or nucleoside analogs that will compete for incorporation into viral genome and when they are they terminate the DNA strand
What are naive patients?
Patients not previously treated with ART are considered to be “naïve”
NRTI SE
Inhibit DNA polymerase γ, blocking production of mtDNA and inhibiting oxydative phosphorylation complexes. This promotes production of cytosolic lactate, and may induce lactic acidosis-hepatic steatosis syndrome.
Which of the NRTIs can cause lactic-acidosis-hepatic steatosis syndrome?
- Didanosine
- Stavudine
- Zidovudine
What is the main DNA polymerase in humans?
DNA polymerase α
What can be a complication of NRTI discontinuation?
Discontinuation of agents that have anti-HBV
activity is associated with increase in HBV titer - HBV flare
Abacavir Contraindications
HLA-B 5701+ patients - can cause hypersensitivity that can be lethal
Zidovudine Contraindications
Stavudine antagonistic - not for co-administration
Which NRTIs are preferred for naive patients?
- Emtractitabine
- Tenofovir
What are NNRTIs?
Nonnucleotide RT Inhibitors
What drug class are these?
- Delavirdine
- Efavirenz
- Etravirine
- Nevirapine
- Rilpivirine
NNRTIs
NNRTI MOA
Noncompetitive inhibitors bind to RT and induce a conformational change that greatly reduces enzyme activity
Are NRTIs and NNRTIs used as mono therapies?
No
NNRTI SE
CYP450 interaction
Efavirenz Contraindications
1st trimester pregnancy or in women planning to conceive
Nevirapine SE
Severe hepatotoxicity
Nevirapine Contraindications
Women with pretreatment CD4 greater than 250 cells/mm and men with CD4 greater than 400 cells/mm
What drug class do the following drugs belong to?
- Ritonavir
- Fosamprenavir
- Atazanavir
- Indinavir
- Nelfinavir
- Saquinavir
- Tipranavir
- Darunavir
Protease Inhibitors
Protease Inhibitor MOA
PIs inhibit HIV aspartyl protease, block
processing of viral proteins required to produce a mature viral particle.
How effective are protease inhibitors?
Highly effective in the majority of patients when used in combination therapy.
What are some drugs that should not be administered alongside protein inhibitors due to CYP metabolism?
- Quinidine
- Rifampin
- Warfarin
- St. John’s Wart
Ritonavir SE
Paresthesia - not well tolerated at high doses that are effective
Why is ritonavir used in ART even though it cannot be tolerated at the needed doses?
Ritonavir is a potent CYP inhibitor that enhances the half life of other protease inhibitors and allows for reduced dose and frequency
What can PIs induce?
Metabolic Syndrome
What are the features of metabolic syndrome?
- Hyperlipidemia
- Diabetes
- Central Obesity
- Atherosclerosis
What dyslipidemia drugs should be avoided in patients on protease inhibitors?
Statins that are CYP3A4 substrates like pravastatin and fluvastatin
Integrase Inhibitor MOA
Inhibits integrase enzyme of HIV that leads to the integration of viral DNA into the host DNA
Raltegravir MOA
Blocks the insertion of reverse-transcribed
viral DNA into the host DNA by binding the Mg++ cofactors required for the strand transfer - integrate inhibitor
What drug class are:
- elvitegravir
- dolutegravir
Integrase Inhibitor
Enfuvirtide MOA
This peptide binds to HIV surface glycoprotein
gp41 to block conformation required for membrane fusion with host cell - fusion inhibitor
What is the route of administration of enfurvitide?
Injection
Maraviroc MOA
Small molecule slowly-reversible antagonist of
the CCR5 interaction with gp120, blocks CCR5-tropic HIV-1 entry
What is the problem of rifampin co-administered with ART?
Rifampin induces CYP enzymes and reduces exposure to PIs and NNRTIs
What is the general recommendation for starting ART?
- 1 NNRTI + 2 NRTI
OR
- 1 PI + 2 NRTI
What is the preferred NNRTI?
Efavirenz
What is the preferred PI combination?
Atazanavir + Rifonavir
Virology Suppression Failure
The inability to achieve or maintain suppression of viral replication to levels below the limit of detection
Immunologic Failure
The inability to achieve and maintain an adequate CD4 T-cell response despite virologic suppression
Should ART ever be mono therapy?
NO
A 29 year-old male was previously diagnosed with M. tuberculosis infection and rifampin treatment was initiated. In a follow up exam, lab results reveal
the patient to be infected with HIV, and lab results are as follows: CD4+ count = 460 cells/mm3
viral load = 41,000 copies/ml resistance testing = HIV1
Which of the following treatment regimens would be a recommended option, if any?
A. efavirenz, tenofovir, and emtricitabine
B. Nevirapine, tenofovir, and emtricitabine
C. Atazanavir, darunavir, and tipranavir
D. Didanosine, abacavir, and lamivudine
E. None of the above
A. efavirenz, tenofovir, and emtricitabine
