Lecture 78 - HIV Therapy

Question 1

Co-Receptor Blocker

Answer 1

Maraviroc (MVC)
binds CCR5
Works for R5 tropic HIV, but not X4 or dual mixed

Question 2

Fusion Blocker

Answer 2

Enfuvirtide(T20, ENF)

huge peptide which binds gp41
given subQ BID

Side effects – injection site abscess

Question 3

Inhibitors of Reverse Transcriptase: Nucleoside RT Inhbitors (NRTIs)

Mechanism

Answer 3

Mechanism: Insert into the DNA product; blocking the action of the RT

Zidovudine(ZDV) aka AZT

DDI/D4T (mitochondrial toxicity)

Lamivudine/Emtricitabine (3TC/FTC)

Abacovir (ABC) – gold standard if tolerated

Tenofovir -(TDF)

Question 4

What is a common side effect of NRTIs? describe some of the manifestations

Answer 4

Common Side Effect: Mitochondiral Toxicity

Mitochondrial toxicity – Mito have their own DNA polymerases; more analogous to the RT in HIV than it is to cellular polymerase

Neuropathy, myopathy, lactic acidosis, pancreatitis

Lipoatrophy
Therefore these drugs poison mitochondrial

Can die of lactic acidosis

Question 5

Inhibitors of RT: Class 2 –Non Nucleoside RT Inhibitors):

Mechanism

Answer 5

Mechanism: Block the RT directly

Nevirapine (NVP)
Efavirenz (EFV) — vivid dream
Etravirine (ETR)
Rilpivirine (RPV)

Question 6

Integrase inhibitors

Mechanism

Answer 6

Raltegravir, RAL
Elvitegravir, EVG – always coformulated with cobistat
Dolutegravir, DTG

Mechanism: inhibition of catalytic activity of integrase

Question 7

Protease Inhibitors:

Mechanism

Answer 7

Prevent the maturation of virions as they bud off the host

Ritonavir, RTV (no longer used)
Indiavir, IDV
Nefinavir, NFV, 
Atazanavir, ATV -- lipid sparing
Tipranavir (TPV) -- intracranial hemorrhage 
Darunavir (DRV) 
Lopinavir/Ritonavir

Question 8

Prescribing a regimen – what are the “backbone” of therapies

Answer 8

2 NRTIs

1) Preferred: Tenofovir/Emtricitabine (TDF/FTC) – once daily dose
2) Alternative: ABC/3TC Abacavir/Lamivudine (once daily)
3) Other: ZDV/Lamivudine (AZT/3TC)

Question 9

Recommendations for Initial regimens

Answer 9

NNRTI + 2 NRTI (Efavirenz + TDF/FTC)

PI + 2 NRTI

1) Atazanavir + TDF/FTC (+Ritonavir)
2) Darunavir + TDF/FTC (+ritonavir)

Integrase Inhbitors + 2 NRTI

1) Dolutegravir + ABC/3TC
2) Dolutegravir + TDF/FTC
3) Elvitegravir (+COBI) + TDF/FTC
4) Raltegravir + TDF/FTC