Anti-Retroviral Drugs

Question 1

Emtricitabine: FTC

Answer 1

NRTI (nucleoside reverse transcriptase inhibitor)

• among the best tolerated of NRTI’s of all AE
• active against HBV

added with tenofovir

Question 2

Tenofovir DF, TDF

Answer 2

NRTI

MOA: Competitive inhibition of HIV-1 reverse transcriptase; incorporated into growing viral DNA chain and causes chain termination

• • this is the only NUCLEOTIDE RTI
• active against HBV

added with emtricitabine

Question 3

Efavirenz, EFV

Answer 3

NNRTI (non-nucleoside reverse transcriptase inhibitor) - binds directly to RT blocking RNA and DNA depdendent DNA polymerase activity
- Different binding site from NRTIs

** don’t use in women with pregnancy or child bearing age

Resistance develops rapidly when used as monotherapy

** recommended initial treatment regimen for Antiretroviral-Naïve Patients- this only has once a day dosing

Question 4

Atazanavir, ATV

Answer 4

PI (protease inhibitor) - involved in cutting the strand

Atazanavir is “boosted” with low dose ritonavir.

Question 5

Darunavir, DRV

Answer 5

PI

Question 6

Lopinavir, LPV

Answer 6

PI

Question 7

Ritonavir, RTV

Answer 7

PI

PIs prevent mature proteins, results in immature, noninfectious viral particles

Use of a PI in combination with other drugs has led to marked clinical improvement and prolonged survival even in patients with advanced HIV infection.

Low-dose ritonavir taken with some other PIs inhibits their metabolism by competing for binding to CYP3A4. This increases their serum concentrations.

It is used in conjunction with atazanavir, darunavir or lopinavir b/c it BOOSTS the level of these three drugs = “ritonavir boosting”

Question 8

Raltegravir, RAL

Answer 8

INSTI (integrase strand transfer inhibitor)

HIV-1 integrase catalyzes the process that results in viral DNA insertion into the host genome. Integrase strand transfer inhibitors (InSTI) block the enzyme’s activity, preventing viral DNA from integrating with cellular DNA.

Question 9

Maraviroc, MVC

Answer 9

CCR5 Antagonist/Entry inhibitor - blocks virus attachment and entry

CCR5 and CXCR4 are the two major co-receptors used by HIV-1 to gain entry into the host cell.

Coreceptor tropism assay should be performed whenever the use of a CCR5 inhibitor is being considered.
Coreceptor tropism testing might also be considered for patients who exhibit virologic failure on a CCR5 inhibitor

Question 10

Enfuvirtide, T-20

Answer 10

Fusion inhibitor

Binds to gp41 subunit of viral envelope glycoprotein & prevents conformational changes required for fusion of viral & cellular membranes

***Must be given by BID subcutaneous injection

Most useful for treatment-experienced patients with persistent HIV-1 replication despite ongoing therapy (not for drug tx naive patients)

Question 11

pattern for ART drugs?

Answer 11

Backbone (two NRTI’s - emtricitabine and tenofovir) and a base (NNRTI, PI, INSTI, CCR5)

Question 12

preferred regimens in drug-naive patients? * know this *

Answer 12

**** efavirenz + tenofovir/emtricitabine **

ritonavir-boosted atazanavir + tenofovir/emtricitabine

ritonavir-boosted darunavir + tenofovir/emtricitabine

raltegravir + tenofovir/emtricitabine

Question 13

drug naive tx for pregnant women?

Answer 13

daily lopinavir/ritonavir + zidovudine/lamivudine

Question 14

when to consider ART?

Answer 14

in patients with CD4 between 500 and 350 (definitely start if CD4<350)

always start regardless of CD4 count in : pregnant women, HIV associated nephropathy, patients co-infected with HBV

Question 15

Genotypic assays vs. phenotypic assays

Answer 15

genotypic assasy: preferred in tx of naive patients- involve sequencing of the reverse transcriptase and protease genes to detect mutations that are known to confer drug resistance.

phenotypic assays: measure the ability of a virus to grow in different concentrations of antiretroviral drugs.

Question 16

ART

Answer 16

Anti-Retroviral therapy

A combination of three or more medications from different classes

Allows decreases doses and thus decreased toxicity

Increases efficacy of treatment in terms of amount of decrease of viral load and return of CD4+ T cell counts

Decreases risk of resistance

Question 17

preferred dual NRTI combo?

Answer 17

tenofovir/emtricitabine + Efavirenz (NNRTI thats preferred except for pregnancy)

Question 18

Preferred PI based regimens?

Answer 18

*** Use of a PI in combination with other drugs has led to marked clinical improvement and prolonged survival even in patients with advanced HIV infection.

PIs prevent mature proteins, results in immature, noninfectious viral particles

atazanavir + ritonavir
darunavir + ritonavir once daily

PLUS Tenofovir/Emtricitabine

Question 19

AE’s of PI’s?

Answer 19

Many PIs can cause gastrointestinal distress, increased bleeding in hemophiliacs, hyperglycemia, insulin resistance and hyperlipidemia, and have been associated with an increased risk of coronary artery disease.

• drug-drug interactions

Question 20

Zidovudine

Answer 20

AZT - this is the first licensed NRTI

its second or third choice now due to serious SE

Question 21

Mechanism of PI’s?

Answer 21

Gag & Gag-Pol gene products code for a polyprotein product
Viral protease clips polyprotein to produce mature proteins that form the structural proteins of the mature virion core.
PIs prevent mature proteins, results in immature, noninfectious viral particles

*** Use of a PI in combination with other drugs has led to marked clinical improvement and prolonged survival even in patients with advanced HIV infection.