Exam 3 Anti-retroviral therapy Flashcards
What are some therapeutic implications of HAART?
- Inhibit RTase (cytoplasmic)
- Inhibit integrase (nuclear)
- Inhibit protease (cytoplasmic)
Anti-retroviral therapy drugs approved by FDA (5)
- Reverse transcriptase inhibitors (RTI)
- Protease inhibitors
- Fusion and entry inhibitors
- Integrase inhibitors
- Pharmacokinetic enhancers
What is a NRTI?
Nucleoside reverse transcriptase inhibitor
NRTI’s are _____ analogs
Nucleoside
First generation NRTI’s are not ____ specific
Viral DNA polymerase (RT)
First NRTI’s introduced
- Azidothymidine (AZT)
- Zidovudine (ZDV)
Functions of NRTI’s
- chain terminators
- block RTase
What are NNRTI’s?
Non-nucleoside reverse transcriptase inhibitors
What do NNRTI’s do?
- Allosteric “non-competitive” inhibition
- Bind to binding site, not enzyme active site
NNRTI’s are synergistic with ____
NRTI’s
Characteristics of protease inhibitors
- Synthetic peptide
- Non-hydrolysable
- stable
What is the function of protease inhibitors?
Block HIV protease (polyprotein cleavage)
What does integrase inhibitor do?
Inhibits irreversible strand transfer step of DNA integration
Raltegravir is an example of:
Integrase inhibitor
Integrase inhibitors are metabolized by:
Cellular glucuronidation
Dolutegravir is an example of:
Integrase inhibitor
____ (integrase inhibitor) was approved in August 2013. It has a prolonged intracellular half life
Dolutegravir
Elvitegravir (EVG) is an example of:
Integrase inhibitor
Elvitegravir is also called:
Vitekta
____ (integrase inhibitor) was approved in September 24, 2014
Elvitegravir
______ is the newest integrase inhibitor (Jan 22, 2021)
Cabotegravir
Examples of pharmacokinetic enhancers
- Cobicistat (COBI); Tyboost
- P450 CYP3A4 enzyme inhibitor
A new attachment inhibitor called _____ binds to ____
Fostemsavir; gp120
Enfuviritide is an example of:
Fusion inhibitor
Enfuviritide binds to ____
gp41
Maraviroc is a _____ inhibitor which acts as a _____
Entry; CCR5 receptor agonist
Which drug has a black box warning?
Maraviroc (hepatotoxicity)
What does it mean if a drug has a black box warning?
Can kill a patient
Ibalizumab is a ____ inhibitor that binds to ____
Entry; CD4
____ is for restricted use only with multidrug-resistant HIV-1
Ibalizumab
____ is always used in combination
Cobicistat (Tyboost)
HAART stands for:
Highly active anti-retroviral therapy
HAART consists of:
Combinations of antiretroviral drugs that block different stages of viral replication
What are the US FDA approved HAART combination products?
- Stribild
- Triumeq
- Evotaz
- Prezcobix
- Genvoya
Stribild (HAART) consists of what antivirals?
- Elvitegravir (II)
- Cobicistat (PE)
Evotaz (HAART) consists of what antivirals?
- Atazanavir
- Cobicistat
Prezcobix (HAART) consists of what antivirals?
- Darunavir
- Cobicistat
Genvoya (HAART) consists of what antivirals?
- Elvitegravir (II)
- Cobicistat (PE)
Stribild was introduced in what year?
2012
In what year was Evotaz, Prezcobix, and Genvoya introduced?
2015
What are the DHSS recommendations for current standard of care?
- All HIV+ patients with an AIDS-defining illness or CD4 count of < 350/microliter
- All pregnant HIV+ patients regardless of CD4 count
- HIV post-exposure prophylaxis (PEP)
If one has CD4+ 350-500/microliter, what is the indication for HAART therapy?
Strong/moderate recommendation
If one has CD4+ >500/microliter, what is the indication for HAART therapy?
Recommended/optional
If one has HBV or HCV co-infection, what is the indication for HAART therapy?
Recommended
If one has HIV-associated nephropathy, what is the indication for HAART therapy?
Recommended
If one has acute HIV infection, what is the indication for HAART therapy?
Optional
Those who undergo HAART therapy have increased _____ and decreased _____
CD4 count; risk of opportunistic infection of death
Vertical transmission of HIV can occur through what ways?
- Ante-partum
- During delivery
- During breastfeeding
Risk of perinatal transmission is significantly reduced with:
Effective antiretroviral (ART/HAART) therapy
____ is needed to reduce perinatal transmission for all pregnant women with HIV infection, regardless of ____
3 part regimen; Viral load or CD4 cell count
HAART therapy and pregnancy: include ____ in ARV regimen, and for newborns Rx is _____
Zidovudine (AZT); AZT first six weeks of life
HIV post-exposure prophylaxis
- 2 drug PEP (NNRTI + NRTI) for 4 weeks
- 3+ drug PEP for 4 weeks
What is PrEP?
Pre-exposure prophylaxis
Success of PrEP in ____ recently reported
MSM
HAART therapy may induce:
Immune restoration disease (IRD)
What is immune restoration disease?
Diseases properly recognized –> larger immune response after immune system restored
In immune reconstitution syndrome, flares of _____ are particularly common
Mycobacterial disease
Co-infection of HIV and TB causes:
- 800x greater risk for developing active TB
- increases transmission of TB
- Increases overall % with latent TB
Side effects of NRTI’s
- Pancreatitis
- Neuropathy
- GI
- Marrow suppression
Side effects of NNRTI’s
- Rash
- Hypersensitivity reactions
Side effects of protease inhibitors (PI’s)
- glucose intolerance
- hyperlipidemia
- lipodystrophy
- breast hypertrophy
- GI
- paresthesia
- Rashes
Side effects of fusion inhibitors
- hypersensitivity
- increased risk of bacterial pneumonia
Lipodystrophy caused by protease inhibitors can cause:
- fat buildup
- fat loss
- increased fat levels in the blood
- increase in blood sugar
On 1/21/21, the US FDA approved ______ as a complete regimen for the treatment of HIV-1 infection in adults. This is the first FDA-approved ____ complete regimen for HIV-infected adults that is administered ____
Cabenuva; injectable; once a month
