Antiretrovirals

Question 1

(1) B cells:

(2) T cells:

Answer 1

formed in bone marrow and produce antibodies after exposure to an antigen.

processed in the thymus (two subtypes)
Subtype 1: Regulator cells also known as helper or CD4 cells (“generals” in army of immune system which recognize “invaders” and summon armies of cells to mount a direct attack)
Subtype 2: Fighter or effector cells also known as cytotoxic or CD8 cells (bind directly to antigen and kill it)

Question 2

2 types of CD4 cells:

Answer 2

(1) Memory cells: those programmed to recognize a specific antigen after it has been previously seen
(2) Naïve cells: non-specific responders

CD4 cells replicate 100 million times a day.

CD4 cells are the target cells of HIV.
patients with low CD4 counts have a poorer prognosis than patients with high CD4 counts.

Question 3

How to achieve viral suppression?

Answer 3

requires the use of combination ARV regimens that generally include three active drugs from two or more drug classes

Question 4

NRTI (Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs))

Answer 4

“dine” “bine” “sine”

Abacavir-ABC
Didanosine-DDI
Emtricitabine-FTC
Lamivudine-3TC
Stavudine-D4T
Tenofovir-TDF
		TAF
Zidovudine-ZDV

Question 5

NNRTI

Answer 5

“vir”

Delavirdine-DLV rarely used
Efavirenz-EFV must take on empty stomach,Can be continued in pregnant women who present in first trimester provided the regimen has provided virologic suppression
Etravirine -ETR Use in patients who are resistant to other NNRTIs
Nevirapine-NVP
Rilpivirine-RPV Used as the NNRTI portion of alternative ART regimen in patients with pre-ART viral load <100,000 copies/ml

Question 6

PI

Answer 6

“navir”

Atazanavir-ATV
Darunavir-DRV
Fosamprenavir-FPV
Indinavir-IDV
Lopinavir/Ritonavir	LPV/r
Nelfinavir-NFV
Ritonavir-RTV
Saquinavir-SQV
Tipranavir-TPV

Question 7

Fusion/Entry Inhibitor

Answer 7

Enfuvirtide-T-20 supplied as dry power for reconstitution, Adverse Events – Injection Site Rxn

Maraviroc-MVC MOA - CCR5 receptor antagonist - prevents CCR5-tropic HIV entry into cells

Question 8

Integrase Inhibitor

Answer 8

“gravir”

MOA - HIV integrase strand transfer inhibitor

Raltegravir-RAL
Dolutegravir-DTG
Elvitegravir-EVG

Question 9

Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs) MOA ADRs

Answer 9

MOA – inhibit the HIV reverse transcriptase enzyme by competing with normal nucleoside/nucleotide triphosphates for incorporation into growing proviral DNA chain. The viral DNA chain elongation is terminated therefore stopping viral replication

First class of ARV drugs approved

Lactic acidosis and hepatic steatosis
GI effects: Abdominal distension, n/v/d
Dyspnea, Facial lipoatrophy
Generalized weakness, fatigue, muscle aches
Labs show low CO2 and anion gap > 16
ALL NRTIs can cause lactic acidosis and hepatic steatosis. Increased risk in women, obesity, pregnancy alcoholics and prolonged use of NRTI

Question 10

Zidovudine (NRTI)

Answer 10

First ARV for HIV
ADRs:
h/a, n,v,d, anorexia, fatigue, 
Myopathy
bone marrow suppression (neutropenia, anemia)
Nail discoloration
Lipoatrophy, increased TGs

Question 11

Didanosine (NRTI)

Answer 11

ADRs – similar to other NRTIs (higher risk of Lactic acidosis and hepatic steatosis)
diarrhea also more common
peripheral neuropathy
Pancreatitis
Hyperuricemia
BMS
retinal depigmentation and optic neuritis

Question 12

Lamivudine (3TC)(NRTI)

Answer 12

Cytosine analogue

Very well tolerated NRTI
GI effects – biggest complaint

Part of dual NRTI portion of initial ART regimens
Once daily dosing
No food affect
No nephrotoxicity

Question 13

Abacavir (ABC) (NRTI)

Answer 13

Guanosine analog

ADR – Well tolerated except for fatal hypersensitivity rxn. Has black box warning. Can occur in 3-5 % of patients.
Symptoms of rxn: fever, rash, fatigue, GI, cough.
Can do HLAB5701 to identify patients at risk

Part of dual NRTI portion of initial ART regimens
Once daily dosing
No food affect
No nephrotoxicity

Question 14

NRTI - Emtricitabine (FTC)

Answer 14

Cytosine analog (similar to lamivudine)
Part of dual NRTI portion of initial ART regimens
QD dosing
Can take without regard to meals
Recommended for HIV/HBV co-infected patients
ADRs – similar to other NRTIs, Also causes headache and unique hyperpigmentation of the palms

Question 15

Tenofovir DF (TDF) nucleoTIDE

Answer 15

Basic advantage over nucleosides is that it already has one phosphate group so it only requires diphoshorylation to be activated
Adenosine analog
Part of dual NRTI portion of initial ART regimens
QD dosing
Can take without regard to meals
Recommended for HIV/HBV co-infected patients
Less toxicity than nucleoside NRTIs
Renal insufficiency - RARE
Osteoporosis
Can also be used for Hep B
Available in combinations for one pill a day

Question 16

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) MOA ADRs

Answer 16

MOA – inhibit the HIV-1 reverse transcriptase enzyme by binding adjacent to the active site, inducing a conformational change that inactivates the enzyme.

Parent molecule is active (unlike the NRTIs)

Second class of ARV drugs approved

Active against HIV-1 only

Potent – but dvp resistance easily (single point mutations)

ADRs – all can cause rashes and hepatotoxicity

Question 17

NNRTI - Nevirapine (NVP)

Answer 17

Rash: Can cause potentially fatal hepatic toxicity & skin rash incl Steven Johnson syndrome & toxic epidermal necrolysis. Closely monitor during first 6-12 weeks of treatment.

Question 18

protease inhibitors MOA ADRS

Answer 18

MOA – Inhibits the enzyme HIV protease by binding to its active site. This prevents the cleavage of the gag-pol precursor polyproteins, resulting in the production of incomplete and non-infectious “virions”

Active vs HIV-1 and HIV-2

Significant GI effects
Paresthesias
Hyperglycemia & insulin resistance
Dyslipidemia
Hepatotoxicity
Lipohypertrophy (fat redistribution)
 risk of bleeding (esp in hemophiliacs)

Question 19

atanazivir (ATV) PI

Answer 19

MOA – azapeptide HIV-1 PI, has greater specificity for HIV protease than the other available PIs. Decreased susceptibility to resistance due to modifications in its structure

Question 20

Cobicistat

Answer 20

Booster - similar to ritonivir in its ability to inhibit liver metabolism
lower doses and side effects while enhancing viral suppression

Question 21

Initial regimen for HIV

Answer 21

• Dolutegrevir/abacavir//lamivudine
• Dolutegrevir plus tenofivir/emtricitabine
• elvitegravir/cobisistat/tenofivir/emtricitabine
• raltegravir plus tenofivir/emtricitabine

Question 22

pregnancy considerations

Answer 22

Intravenous (IV) zidovudine (ZDV) infusion to the mother during labor is recommended if maternal HIV RNA is ≥400 copies/mL
Efavirenz (Sustiva): is teratogenic

Question 23

Significant exposures to any for the following may pose a risk for bloodborne pathogen transmission and require further evaluation:

Answer 23

Blood
Cerebrospinal fluid
Peritoneal fluid
Semen
Synovial fluid
Pericardial fluid
Vaginal secretions
Pleural fluid
Amniotic fluid

Question 24

Body fluids that do NOT pose a risk of bloodborne pathogen transmission unless visibly contaminated with blood include:

Answer 24

Urine
Stool
Tears
Gastric secretions or vomitus
Sweat
Nonpurulent sputum 
Nasal discharge

Question 25

PEP info

Answer 25

should be initiated within 2 hours of exposure and treated for 28 days

Question 26

HIV PEP regimen

Answer 26

raltegravir 400 mg BID + Truvada

Question 27

PrEP

Answer 27

Pre-exposure prophylaxis, or PrEP, is a way for people who do not have HIV but who are at substantial risk of getting it to prevent HIV infection by taking a pill every day. The pill (brand name Truvada) contains two medicines (tenofovir and emtricitabine) that are used in combination with other medicines to treat HIV. When someone is exposed to HIV through sex or injection drug use, these medicines can work to keep the virus from establishing a permanent infection.