HIV

Question 1

HIV therapy initiated when patients present with AIDS-defining illness, CD4<500, or high viral load.

Answer 1

HAART - Highly active antiretroviral therapy

Question 2

3 Drugs making up the HAART regimen to prevent resistance

Answer 2

2 nucleoside reverse transcriptase inhibitors (NRTIs) + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) OR 1 protease inhibitor OR 1 integrase inhibitor

Question 3

What are the main protease inhibitors

Answer 3

NAVIR (never) TEASE a PROTEASE - Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir

Question 4

Mechanism of Protease inhibitors (-Navirs)

Answer 4

Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.

Question 5

Toxicity of Protease inhibitors

Answer 5

Ritonavir can “boost” other drug concentrations by inhibiting cytP450. Also, hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy. Nephropathy

Question 6

What toxicity is specific to indinavir

Answer 6

Hematuria

Question 7

What are the main NRTIs?

Answer 7

Abacavir (ABC), Didanosine (ddl), Emtricitabine (FTC), Tenofovir (TDF),

Zidovudine (ZDV, formerly AZT), Lamivudine (3TC), Stavudine (d4T),

Question 8

Mechanism of the NRTIs

Answer 8

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’ OH group). Tenofovir is a nucleoTide; the others are nucleosides and need to be phosphorylated to be active.

Question 9

What is ZDV used for?

Answer 9

General prophylaxis and during pregnancy to decrease risk of fetal transmission

Question 10

What are toxicities of NRTIs - Vudines?

Answer 10

Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor (G-CSF) and erythropoietin, peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), anemia (ZDV), pancreatitis (didanosine)

Question 11

What are the main NNRTIs?

Answer 11

Delavirdine, Efavirenz, Nevirapine (DEN)

Question 12

What is the mechanism of NNRTIs?

Answer 12

Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides

Question 13

Toxicity of NNRTIs

Answer 13

Rash and hepatotoxicity are common to all NNRTIs. Vivid dreams and CNS symptoms are common with efavirenz. Delvirdine and efavirenz are contraindicated in pregnancy

Question 14

What are the main Integrase inhibitors

Answer 14

Raltegravir

Question 15

What is the mechanism of integrase inhibitors

Answer 15

Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase

Question 16

What is the main toxicity of Raltegravir

Answer 16

Hypercholesterolemia

Question 17

What are the main Fusion inhibitors?

Answer 17

Enfuvirtide and Maraviroc

Question 18

What is the mechanism of Enfuvirtide?

Answer 18

Binds gp41, inhibiting viral entry

Question 19

What is the main toxicity of enfuvirtide?

Answer 19

Skin reaction at injection sites

Question 20

What is the mechanism of Maraviroc?

Answer 20

Binds CCR5 on surface of T cells/monocytes, inhibiting interaction with gp120