Caldwell LOs

Question 1

2 goals of anti-HIV tx

Answer 1

- chronic ds mngt:
achieve durable virologic suppression
stabilize/restore immune function
maintain/improve pt's quality of life
reduce HIV-related mortality & morbidity

Question 2

key viral enzyme that converts viral RNA to DNA

Answer 2

reverse transcriptase

Question 3

analyze how NRTIs reduce viral multiplication

Answer 3

• NRTIs only protect newly infected cells
• MOA:
  targets early and essential step in HIV replication
  substrates for reverse transcriptase
  inhibit RT by incorporating false nucleic acids into new proviral DNA
  lack 3’-OH group so incorporating them into DNA terminates chain elongation

Question 4

interpret where NNRTIs bind and how they inhibit viral reproduction

Answer 4

• inhibit RT by binding ADJACENT to enzyme active site & inducing conformational changes
• only protect newly infected cells
• no need for phosphorylation
• similar toxicities and resistance profiles as NRTIs
• hepatic metabolism, potential for interactions
• effective ONLY against HIV-1

Question 5

describe at what stage of infection both NRTIs and NNRTIs work and analyze why.

Answer 5

• only effective in newly infective cells

- they both work on RT, just in slightly different ways

Question 6

describe importance of protease in viral reproduction and thus how protease inhibitors affect it.

Answer 6

• protease is an essential enzyme for viral survival and infectivity; cleaves viral polyprotein into active viral enzymes
• PIs bind REVERSIBLY to the ACTIVE site of the HIV protease; viral particles become immature and noninfectious; PIs inhibit viral replication in any infected cells

Question 7

unique indicator for enfuvirtide

Answer 7

• advanced HIV-1 infection pts
• ongoing viral replication despite ARV therapy
• uses injection formulation

Question 8

what types of drugs are given in PI-based HAART regimen

Answer 8

PI + 2 NRTIs
Ex: lopinavir/ritonavir +
(zidovudine or stavudine) +
lamivudine

Question 9

advantage of NNRTI-based regimens over PI-based regimens as HAART

Answer 9

• uses NNRTI + 2 NRTIs

- advantages: simple regimens, less fat maldistribution dyslipidemia, and saves PI options for future use

Question 10

2 significant tests to determine severity of HIV infection

Answer 10

• plasma HIV RNA levels
• CD4 T-cell counts
• HIV RNA levels

Question 11

most prominent s/e to NRTIs zidovudine, stavudine, and didanosine

Answer 11

• ziduvudine: bone marrow suppression
• stavudine: peripheral neuropathy
• didanosine: pancreatitis & peripheral neuropathy

Question 12

2 indications that drug failure occurred w/ ARVs

Answer 12

• inadequate viral suppression

- unsatisfactory increase in CD4 count

Question 13

major adverse effect to ARVs and how it is monitored and defined

Answer 13

• HEPATOTOXICITY
• defined as 3-5x increase in serum transaminases
• can be w/ or w/o clinical hepatitis
• majority of these pts are asx
• may resolve spontaneously
• mostly assoc w/ NNRTIs and PIs

Question 14

enzyme that metabolizes all PIs

Answer 14

• all metabolized w/ CYP3A4

Question 15

2 NRTIs preferred for tx of HIV

Answer 15

emtricitabine & tenofovir

Question 16

population that should NOT receive efavirenz

Answer 16

prego women