Antivirals

Question 1

Significance of HIV high rate of mutation of HIV per replicaition cycle

Answer 1

1. Great potential for genotypic variation

2. Need for multi-drug treatment regimens (at least 3)

Question 2

Selection criteria: which drug should you avoid if pt has

1. Allergy hx
2. Pregnant
3. Kidney disease

Answer 2

1. Allergy hx
   - abacavir
2. Pregnant
   - efavirenz
3. Kidney disease
   - tenofovir

Question 3

Initiation of therapy:
Backbone
Base

Answer 3

Backbone
2 NRTIs:
Tenofovir - Emtricitabine
or 1 NRTI and 1 Integrase Inhibitors

Base:
1. Integrase inhibitor
or
2. Boosted PI combo
or
3. NNRTI
or
4. CCR5 antagonist

Question 4

NRTIs MOA

Answer 4

prevents genome replication and establishment of provirus

Question 5

Which are the only NRTIs that are eliminated via hepatic glucuronidation

Answer 5

Abacavir and Zidovudine

*rest are renal excretion

Question 6

Side effects of NRTIs

Answer 6

1. myopathy
2. neuropathy
3. Bone marrow suppression
4. Lactic acidosis
5. Pancreatitic / hepatic steatosis
6. Renal impairment (with tenofovir)

Question 7

Which of the antivirals do not require activation by intracellular kinases, NNRTIs or NRTIs?

Answer 7

NNRTIs

• prevent genome replication - establishment of provirus

Question 8

SIde effect of efavirenz

Answer 8

Severe CNS effects
Rash
HA
cant [ ]

*only retroviral agent in preg category D

Question 9

Nevirapine side effect

Answer 9

serious cutaneous rxns

Question 10

Etravirine side effect

Answer 10

Rash (less than nevirapine, but still bad stuff)

Question 11

Adverse drug rxns of PIs

Answer 11

1. GI distress
2. Hyperglycemia
3. Hyperlipidemia
4. INcreased risk of CAD

Question 12

Integrase strand transfer inhibitors (INSTIs)

- IIs

Answer 12

1. Dolutegravir
2. Raltegravir
3. Elvitegravir

Question 13

Goal of antiretroviral therapy is to suppress HIV viral load to how many copies?

Answer 13

Less than 50

Question 14

When is resistance testing recommended?

Answer 14

When pt is first seen, regardless of when therapy is first started

Question 15

Drug combo for prevention of perinatal HIV transmission

Answer 15

PI: Ritonavir-Lopinavir (rLPV)
\+
NRTI: Zidovudine (ZDV)
\+ 
NRTI: 
Lamivudine (3TC)

Question 16

Once NRTIs are incorporated into viral DNA, how do these antiretrovirala block further replication?

Answer 16

They terminate strand elongation due to their lack of 3’OH groups

Question 17

How is tenofovir different from the other NRTIs?

Answer 17

Tenofovir is a nucleoTide
and does not need to be phosphorylated to become activated (into their triphosphorylated fully active forms) like the other NRTIs

*NNRTIs do not require phosphorylation

Question 18

Unlike NRTIs that bind to the active site of HIV reverse transcriptase, where do NNRTIs bind?

Answer 18

a non catalytic hydrophobic pocket in the p66 subunit of HIV rev. transcriptase –>
induce conformational change

(noncompetitively inhibit HIV rev trans.)

Question 19

does developing resistance to the older NNRTIs mean that you developed resistance to all NNRTIs?
What about resistance to one PI?

Answer 19

yes
(except the newest one, etravirine)

No to PI, resistance is only specific for that PI

Question 20

pts with drug resistance to both PIs and NNRTIs can use which drug?

Answer 20

the newest NNRTI, etravirine

Question 21

Preg D category,
Rash
CNS effects
Hepatotoxicity

Answer 21

Efavirenz

NNRTI

Question 22

How do protease inhibitors work?

Answer 22

prevent maturation of new virus by inhibiting HIV-1 protease (aspartyl protease)
(cant cleave HIV mRNA into fxnal parts)