HIV Drugs

Question 1

Factors that determine pharmacological success

Answer 1

• Ideally > 3 active drugs from at least 2 classes
• Adverse DD or DF interactions
• Adherence to the drug regimen
• Viral/patient/immunological factors

Question 2

NRTIs

Class Characteristics

Answer 2

• Must be activated by human kinases to triphosphate
• Competitively inhibit reverse transcriptase and terminate chain elongation if incorporated
• All have BBW for lactic acidosis
• Most excreted/secreted by the kidney
• HIV usually needs several resistance mutations to confer high level resistance

Question 3

Abacavir (Ziagen) ABC

Answer 3

• NRTI
• Preferred
• Hypersensitivity reactions (never rechallenge, HLA-B5701)

Question 4

Emtricitabine (Emtriva) FTC

Answer 4

• NRTI
• Preferred
• Activity vs. Hep B (no indication)
• Discoloration of palms and soles in non-Caucasians

Question 5

Lamivudine (Epivir) 3TC

Answer 5

• NRTI
• Preferred
• Active vs. HBV
• Just one HIV mutation in HIV-RT gene causes many fold resistance

Question 6

Tenofovir (Viread) TDF/TAF

Answer 6

• NRTI
• Preferred
• Rare proximal tubulopathy
• TDF-FTC indicated for Pre-exposure prophylaxis (PrEP)

Question 7

Zidovudine (Retrovir) AZT

Answer 7

• NRTI
• Special
• Used for prevention of perinatal transmission
• Unique side effects (cytopenia, myopathy, HA, nausea)

Question 8

NNRTIs

Class Characteristics

Answer 8

• Non-competitive binding to reverse transcriptase causes change in protein shape and loss of function
• Toxicity (hypersensitivity, rash/hepatitis)
• Metabolized by various enzymes in liver (3A4, 2B6)
• HIV needs only ONE resistance mutation to confer high level resistance to all agents

Question 9

Efavirenz (Sustiva) EFV

Answer 9

• NNRTI
• Alternative
• Take on empty stomach
• CNS perturbations
• Avoid in pregnancy

Question 10

Etravirine (Intelence) ETV

Answer 10

• NNRTI
• Special
• Typically requires > 2 resistance mutations
• Rash

Question 11

Rilpivirine (Edurant) RPV

Answer 11

• NNRTI
• Alternative
• Less effective in naive patients with VL > 100,000
• Depression, Additive QTc effect

Question 12

Maravironc (Selzentry)

Answer 12

• CCR5 Inhibitor
• Special
• Tropism test is needed to determine whether the HIV strain uses CCR5 (trofile test)
• BBW for hepatitis/hypersensitivity
• Metabolized by 3A4

Question 13

Enfuvirtide (Fuzeon)

Answer 13

• gp41 fusion inhibitor
• Special
• It is a linear 36 amino acid synthetic molecule
• Toxicity is generally injection site reaction

Question 14

HIV Integrase Inhibitors

Class Characteristics

Answer 14

• Inhibit strand transfer of integrase activity
• Toxicity (hypersensitivity, increased CPK, insomnia)
• Metabolized by UGT1A1
• Caution simultaneous administration with products containing polyvalent cations
• Resistance mutations identified

Question 15

Raltegravir (Isentress)

Answer 15

• II
• Preferred
• BID
• Creatine Kinase increase

Question 16

Elvitegravir (Stribild)

Answer 16

• II
• Preferred
• Coformulated with PK booster (cobicistat) and FTC-TDF
• Cobicistat inhibits creatinine secretion

Question 17

Dolutegravir (Tivicay)

Answer 17

• II
• Preferred
• Insomnia
• Benign increase in SCr

Question 18

Protease Inhibitors

Class Characteristics

Answer 18

• Peptidomimetics
• Adverse effects (increased blood lipids and glucose, GI intolerance)
• Liver/gut metabolized (3A4)
• HIV usually needs several resistance mutations to confer moderate to high-level resistance (high barrier)

Question 19

Atazanavir (Reyatz) ATZ

Answer 19

• PI
• Alternative
• Hyperbilirubinemia via inhibition of UGT1A1
• Boosted with ritonavir/cobicistat

Question 20

Darunavir (Prezista) DRV

Answer 20

• PI
• Preferred
• Must be boosted
• Rash (sulfonamide)
• High genetic barrier

Question 21

Ritonavir (Norvir) RTV

Answer 21

• PI
• PK enhancer
• Not used alone only to boost
• 3A4 inhibitor
• SE from full dose